Potential Use of Chemoprotectants against the Toxic Effects of Cyanotoxins: A Review
Abstract
:1. Introduction
2. Microcystins
2.1. Transporter Inhibitors
2.2. Anti-Inflammatory Agents
2.3. Osmotic Agents
2.4. Antioxidants
2.4.1. N-Acetylcysteine (NAC)
1 General Aspects
2 Protective Effects of NAC against MCs
2.4.2. Selenium (Se)
1 General Aspects
2 Protective Effects of Se and Derivatives against MCs
2.4.3. Vitamin E
1 General Aspects
2 Protective Effects of Vitamin E against MCs
2.4.4. Other Antioxidants
2.4.5. Comparison of the Effectiveness of the Various Antioxidant Substances in MC-Intoxicated Fish
2.5. Diverse Mechanisms
3. Cylindrospermopsin
3.1. Protective Effects of NAC against CYN
3.2. L-carnitine
3.2.1. General Aspects
3.2.2. Protective Effects of L-carnitine against CYN
3.3. Protective Effects of Vitamin E against CYN
3.4. Global Comparison of Antioxidant Effectiveness in CYN-Intoxicated Fish
4. Conclusions
Acknowledgments
Conflicts of Interest
References
- Martins, J.C.; Vasconcelos, V.M. Microcystin distribution and dynamics in aquatic organisms—A review. J. Toxicol. Environ. Health Part B 2009, 12, 1–18. [Google Scholar] [CrossRef] [PubMed]
- Testai, E.; Buratti, F.M.; Funari, E.; Manganelli, M.; Vichi, S.; Arnich, N.; Biré, R.; Fessard, V.; Sialehaamoa, A. Review and analysis of occurrence, exposure and toxicity of cyanobacteria toxins in food. EFSA Support. Publ. 2016, 13, 309. [Google Scholar] [CrossRef]
- Nogueira, I.C.G.; LOBO-da-Cunha, A.; Vasconcelos, V.M. Effects of Cylindrospermopsis raciborskii and Aphanizomenon ovalisporum (cyanobacteria) ingestion on Daphnia magna midgut and associated diverticula epithelium. Aquat. Toxicol. 2006, 80, 194–203. [Google Scholar] [CrossRef] [PubMed]
- Puerto, M.; Jos, A.; Pichardo, S.; Moyano, R.; Blanco, A.; Cameán, A.M. Acute exposure to pure cylindrospermopsin results in oxidative stress and pathological alterations in tilapia (Oreochromis niloticus). Environ. Toxicol. 2014, 29, 371–385. [Google Scholar] [CrossRef] [PubMed]
- Svirčev, Z.; Lujić, J.; Marinović, Z.; Drobac, D.; Tokodi, N.; Stojiljković, B.; Meriluoto, J. Toxicopathology induced by microcystins and nodularin: A histopathological review. J. Environ. Sci. Health C Environ. Carcinog. Ecotoxicol. Rev. 2015, 33, 125–167. [Google Scholar] [CrossRef] [PubMed]
- Bazin, E.; Huet, S.; Jarry, G.; Le Hégarat, L.; Munday, J.S.; Humpage, A.R.; Fessard, V. Cytotoxic and genotoxic effects of cylindrospermopsin in mice treated by gavage or intraperitoneal injection. Environ. Toxicol. 2012, 27, 277–284. [Google Scholar] [CrossRef] [PubMed]
- Zegura, B. An Overview of the Mechanisms of Microcystin-LR Genotoxicity and Potential Carcinogenicity. Mini Rev. Med. Chem. 2016, 16, 1042–1062. [Google Scholar] [CrossRef] [PubMed]
- Guzmán-Guillén, R.; Lomares Manzano, I.; Moreno, I.M.; Prieto Ortega, A.I.; Moyano, R.; Blanco, A.; Cameán, A.M. Cylindrospermopsin induces neurotoxicity in tilapia fish (Oreochromis niloticus) exposed to Aphanizomenon ovalisporum. Aquat. Toxicol. 2015, 161, 17–24. [Google Scholar] [CrossRef] [PubMed]
- Hu, Y.; Chen, J.; Fan, H.; Xie, P.; He, H. A review of neurotoxicity of microcystins. Environ. Sci. Pollut. Res. 2016, 23, 7211–7219. [Google Scholar] [CrossRef] [PubMed]
- Rogers, E.H.; Zehr, R.D.; Gage, M.I.; Humpage, A.R.; Falconer, I.R.; Marr, M.; Chernoff, N. The cyanobacterial toxin, cylindrospermopsin, induces fetal toxicity in the mouse after exposure late in gestation. Toxicon 2007, 49, 855–864. [Google Scholar] [CrossRef] [PubMed]
- El Ghazali, I.; Saqrane, S.; Carvalho, A.P.; Youness, O.; Oudra, B.; del Campo, F.F.; Vasconcelos, V. Compensatory growth induced in zebrafish larvae after pre-exposure to a Microcystis aeruginosa natural bloom extract. Int. J. Mol. Sci. 2009, 10, 133–146. [Google Scholar] [CrossRef] [PubMed]
- Qi, M.; Dang, Y.; Xu, Q.; Yu, L.; Liu, C.; Yuan, Y.; Wang, J. Microcystin-LR induced developmental toxicity and apoptosis in zebrafish (Danio rerio) larvae by activation of ER stress response. Chemosphere 2016, 157, 166–173. [Google Scholar] [CrossRef] [PubMed]
- Sibaldo de Almeida, C.; Costa de Arruda, A.C.; Caldas de Queiroz, E.; Matias de Lima Costa, H.T.; Barbosa, P.F.; Araújo Moura Lemos, T.M.; Oliveira, C.N.; Pinto, E.; Schwarz, A.; Kujbida, P. Oral exposure to cylindrospermopsin in pregnant rats: Reproduction and foetal toxicity studies. Toxicon 2013, 74, 127–129. [Google Scholar] [CrossRef] [PubMed]
- Chen, L.; Chen, J.; Zhang, X.; Xie, P. A review of reproductive toxicity of microcystins. J. Hazard. Mater. 2016, 301, 381–399. [Google Scholar] [CrossRef] [PubMed]
- Buratti, F.M.; Manganelli, M.; Vichi, S.; Stefanelli, M.; Scardala, S.; Testai, E.; Funari, E. Cyanotoxins: Producing organisms, occurrence, toxicity, mechanism of action and human health toxicological risk evaluation. Arch. Toxicol. 2017, in press. [Google Scholar] [CrossRef] [PubMed]
- Sivonen, K.; Jones, G. Cyanobacterial Toxins. In Toxic Cyanobacteria in Water: A Guide to Their Public Health Consequences, Monitoring and Management; Chorus, I., Bartam, J., Eds.; E & FN Spon: London, UK, 1999; pp. 41–111. [Google Scholar]
- Fischer, W.J.; Altheimer, S.; Cattori, V.; Meier, P.J.; Dietrich, D.R.; Hagenbuch, B. Organic anion transporting polypeptides expressed in liver and brain mediate uptake of microcystin. Toxicol. Appl. Pharmacol. 2005, 203, 257–263. [Google Scholar] [CrossRef] [PubMed]
- Wood, R. Acute animal and human poisonings from cyanotoxin exposure—A review of the literature. Environ. Int. 2016, 91, 276–282. [Google Scholar] [CrossRef] [PubMed]
- Dawson, R.M. The toxicology of microcystins. Toxicon 1998, 36, 953–962. [Google Scholar] [CrossRef]
- Campos, A.; Vasconcelos, V. Molecular mechanisms of microcystin toxicity in animal cells. Int. J. Mol. Sci. 2010, 11, 268–287. [Google Scholar] [CrossRef] [PubMed]
- Pereira, S.; Vasconcelos, V.; Antunes, A. The phosphoprotein phosphatase family of Ser/Thr phosphatases as principal targets of naturally occurring toxins. Crit. Rev. Toxicol. 2010, 41, 83–110. [Google Scholar] [CrossRef] [PubMed]
- Ding, W.X.; Nam Ong, C. Role of oxidative stress and mitochondrial changes in cyanobacteria-induced apoptosis and hepatotoxicity. FEMS Microbiol. Lett. 2003, 220, 1–7. [Google Scholar] [CrossRef]
- Pflugmacher, S.; Wiegand, C.; Oberemm, A.; Beattie, K.A.; Krause, E.; Codd, G.A.; Steinberg, C.E. Identification of an enzymatically formed glutathione conjugate of the cyanobacterial hepatotoxin microcystin-LR: The first step of detoxication. Biochim. Biophys. Acta 1998, 1425, 527–533. [Google Scholar] [CrossRef]
- Puerto, M.; Pichardo, S.; Jos, A.; Prieto, A.I.; Sevilla, E.; Frías, J.E.; Cameán, A.M. Differential oxidative stress responses to pure Microcystin-LR and Microcystin-containing and non-containing cyanobacterial crude extracts on Caco-2 cells. Toxicon 2010, 55, 514–522. [Google Scholar] [CrossRef] [PubMed]
- Zhou, M.; Tu, W.; Xu, J. Mechanisms of microcystin-LR-induced cytoskeletal disruption in animal cells. Toxicon 2015, 101, 92–100. [Google Scholar] [CrossRef] [PubMed]
- Amado, L.L.; Montserrat, J.M. Oxidative stress generation by microcystins in aquatic animals: Why and how. Environ. Int. 2010, 36, 226–235. [Google Scholar] [CrossRef] [PubMed]
- Zegura, B.; Straser, A.; Filipic, M. Genotoxicity and potential carcinogenicity of cyanobacterial toxins—A review. Mutat. Res. 2011, 727, 16–41. [Google Scholar] [CrossRef] [PubMed]
- IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Ingested Nitrate and Nitrite and Cyanobacterial Peptide Toxins Volume 94; WHO Press: Lyon, France, 2010. [Google Scholar]
- Atencio, L.; Moreno, I.; Prieto, A.I.; Moyano, R.; Molina, A.M.; Cameán, A.M. Acute effects of microcystins MC-LR and MC-RR on acid and alkaline phosphatase activities and pathological changes in intraperitoneally exposed Tilapia fish (Oreochromis sp.). Toxicol. Pathol. 2008, 36, 449–458. [Google Scholar] [CrossRef] [PubMed]
- Puerto, M.; Pichardo, S.; Jos, A.; Cameán, A.M. Comparison of the toxicity induced by microcystin-RR and microcystin-YR in differentiated and undifferentiated Caco-2 cells. Toxicon 2009, 54, 161–169. [Google Scholar] [CrossRef] [PubMed]
- Xu, C.; Shu, W.Q.; Qiu, Z.Q.; Chen, J.A.; Zhao, Q.; Cao, J. Protective effects of green tea polyphenols against subacute hepatotoxicity induced by microcystin-LR in mice. Environ. Toxicol. Pharmacol. 2007, 24, 140–148. [Google Scholar] [CrossRef] [PubMed]
- Wang, J.; Yu, S.; Jiao, S.; Lv, X.; Ma, M.; Du, Y. κ-Selenocarrageenan prevents microcystin-LR-induced hepatotoxicity in BALB/c mice. Food Chem. Toxicol. 2013, 59, 303–310. [Google Scholar] [CrossRef] [PubMed]
- Rao, P.V.L.; Gupta, N.; Jayaraj, R. Screening of certain chemoprotectants against cyclic peptide toxin microcystin LR. Indian. J. Pharmacol. 2004, 36, 87–92. [Google Scholar]
- Adams, W.H.; Stoner, R.D.; Adams, D.G.; Read, H.; Slatkin, D.N.; Siegelman, H.W. Prophylaxis of cyanobacterial and mushroom cyclic peptide toxins. J. Pharmacol. Exp. Ther. 1989, 249, 552–556. [Google Scholar] [PubMed]
- Hermansky, S.J.; Casey, P.J.; Stohs, S.J. Cyclosporin A—A chemoprotectant against microcystin-LR toxicity. Toxicol. Lett. 1990, 54, 279–285. [Google Scholar] [CrossRef]
- Hermansky, S.J.; Stohs, S.J.; Eldeen, Z.M.; Roche, V.F.; Mereish, K.A. Evaluation of potential chemoprotectants against microcystin-LR hepatotoxicity in mice. J. Appl. Toxicol. 1991, 11, 65–73. [Google Scholar] [CrossRef] [PubMed]
- Kaya, K. Toxicology of Microcystins. In Toxic Microcystis; Watanabe, M.F., Harada, K., Carmichael, W.W., Fijiki, H., Eds.; CRC Press: Boca Raton, FL, USA, 1996; Chapter 8; pp. 175–202. [Google Scholar]
- Ding, W.X.; Shen, H.M.; Ong, C.N. Microcystic cyanobacteria extract induces cytoskeletal disruption and intracellular glutathione alteration in hepatocytes. Environ. Health Perspect. 2000, 108, 605–609. [Google Scholar] [CrossRef] [PubMed]
- Puerto, M.; Prieto, A.I.; Pichardo, S.; Moreno, I.; Jos, A.; Moyano, R.; Cameán, A.M. Effects of dietary N-acetylcysteine (NAC) on the oxidative stress induced in tilapia (Oreochromis niloticus) exposed to a microcystin-producing cyanobacterial water bloom. Environ. Toxicol. Chem. 2009, 28, 1679–1686. [Google Scholar] [CrossRef] [PubMed]
- Puerto, M.; Prieto, A.I.; Jos, A.; Moreno, I.; Moyano, R.; Blanco, A.; Cameán, A.M. Dietary N-acetylcysteine (NAC) prevents histopathological changes in tilapias (Oreochromis niloticus) exposed to a microcystin-producing cyanobacterial water bloom. Aquaculture 2010, 306, 35–48. [Google Scholar] [CrossRef]
- Xue, L.; Li, J.; Li, Y.; Chu, C.; Xie, G.; Qin, J.; Yang, M.; Zhuang, D.; Cui, L.; Zhang, H.; et al. N-acetylcysteine protects Chinese Hamster ovary cells from oxidative injury and apoptosis induced by microcystin-LR. Int. J. Clin. Exp. Med. 2015, 8, 4911–4921. [Google Scholar] [PubMed]
- Takenaka, S.; Otsu, R. Effects of L-cysteine and reduced glutathione on the toxicities of microcystin LR: The effect for acute liver failure and inhibition of protein phosphatase 2A activity. Aquat. Toxicol. 1999, 48, 65–68. [Google Scholar] [CrossRef]
- Stoner, R.D.; Adams, W.H.; Slatkin, D.N.; Siegelman, H.W. Cyclosporine A inhibition of Microcystin toxins. Toxicon 1990, 28, 569–573. [Google Scholar] [CrossRef]
- Thompson, W.L.; Pace, J.G. Substances that protect cultured hepatocytes from the toxic effects of microcystin-LR. Toxicol. In Vitro 1992, 6, 579–587. [Google Scholar] [CrossRef]
- Runnegar, M.; Berndt, N.; Kaplowitz, N. Microcystin uptake and inhibition of protein phosphatases: Effects of chemoprotectants and self-inhibition in relation to known hepatic transporters. Toxicol. Appl. Pharmacol. 1995, 134, 264–272. [Google Scholar] [CrossRef] [PubMed]
- Rao, P.V.L.; Jayaraj, R.; Bhaskar, A.S.B. Protective efficacy and the recovery profile of certain chemoprotectants against lethal poisoning by microcystin-LR in mice. Toxicon 2004, 44, 723–730. [Google Scholar] [CrossRef] [PubMed]
- Shi, J.; Deng, H.; Pan, H.; Xu, Y.; Zhang, M. Epigallocatechin-3-gallate attenuates microcystin-LR induced oxidative stress and inflammation in human umbilical vein endothelial cells. Chemosphere 2017, 168, 25–31. [Google Scholar] [CrossRef] [PubMed]
- Jayaraj, R.; Deb, U.; Bhaskar, A.S.B.; Prasad, G.B.K.S.; Rao, P.V.L. Hepatoprotective efficacy of certain flavonoids against microcystin induced toxicity in mice. Environ. Toxicol. 2007, 22, 472–479. [Google Scholar] [CrossRef] [PubMed]
- Amado, L.L.; Garcia, M.L.; Pereira, T.C.; Yunes, J.S.; Bogo, M.R.; Monserrat, J.M. Chemoprotection of lipoic acid against microcystin-induced toxicosis in common carp (Cyprinus carpio, Cyprinidae). Comp. Biochem. Physiol. C Toxicol. Pharmacol. 2011, 154, 146–153. [Google Scholar] [CrossRef] [PubMed]
- Lindsay, J.; Metcalf, J.S.; Codd, G.A. Protection against the toxicity of microcystin-LR and cylindrospermopsin in Artemia salina and Daphnia spp. by pre-treatment with cyanobacterial lipopolysaccharide (LPS). Toxicon 2006, 48, 995–1001. [Google Scholar] [CrossRef] [PubMed]
- Blankson, H.; Grotterod, E.M.; Seglen, P.O. Prevention of toxin-induced cytoskeletal disruption and apoptotic liver cell death by the grapefruit flavonoid, naringin. Cell Death Differ. 2000, 7, 739–746. [Google Scholar] [CrossRef] [PubMed]
- Xie, L.; Hanyu, T.; Futatsugi, N.; Komatsu, M.; Alan, D.; Steinman, A.D.; Park, H.D. Inhibitory effect of naringin on microcystin-LR uptake in the freshwater snail Sinotaia histrica. Environ. Toxicol. Pharmacol. 2014, 38, 430–437. [Google Scholar] [CrossRef] [PubMed]
- Takumi, S.; Ikema, S.; Hanyu, T.; Shima, Y.; Kurimoto, T.; Shiozaki, K.; Sugiyama, Y.; Park, H.D.; Ando, S.; Furukawa, T.; et al. Naringin attenuates the cytotoxicity of hepatotoxin microcystin-LR by the curious mechanisms to OATP1B1- and OATP1B3-expressing cells. Environ. Toxicol. Pharmacol. 2015, 39, 974–981. [Google Scholar] [CrossRef] [PubMed]
- Herfindal, L.; Myhren, L.; Kleppe, R.; Krakstad, C.; Selheim, F.; Jokela, J.; Sivonen, K.; Døskeland, S.O. Nostocyclopeptide-M1: A Potent, Nontoxic Inhibitor of the Hepatocyte Drug Transporters OATP1B3 and OATP1B1. Mol. Pharm. 2011, 8, 360–367. [Google Scholar] [CrossRef] [PubMed]
- Gehringer, M.M.; Downs, K.S.; Downing, T.G.; Naude, R.J.; Shephard, E.G. An investigation into the effect of selenium supplementation on microcystin hepatotoxicity. Toxicon 2003, 41, 451–458. [Google Scholar] [CrossRef]
- Atencio, L.; Moreno, I.; Jos, A.; Prieto, A.I.; Moyano, R.; Blanco, A.; Cameán, A.M. Effects of dietary selenium on the oxidative stress and pathological changes in tilapia (Oreochromis niloticus) exposed to a microcystin-producing cyanobacterial water bloom. Toxicon 2009, 53, 269–282. [Google Scholar] [CrossRef] [PubMed]
- Gan, N.Q.; Mi, L.X.; Sun, X.Y.; Dai, G.F.; Chung, F.L.; Song, L.R. Sulforaphane protects microcystin-LR-induced toxicity through activation of the Nrf2-mediated defensive response. Toxicol. Appl. Pharmacol. 2010, 247, 129–137. [Google Scholar] [CrossRef] [PubMed]
- Sun, X.; Mi, L.; Liu, J.; Song, L.; Chung, F.L.; Gan, N. Sulforaphane prevents microcystin-LR-induced oxidative damage and apoptosis in BALB/c mice. Toxicol. Appl. Pharmacol. 2011, 255, 9–17. [Google Scholar] [CrossRef] [PubMed]
- Gehringer, M.M.; Govender, S.; Shah, M.; Downing, T.G. An investigation of the role of vitamin E in the protection of mice against microcystin toxicity. Environ. Toxicol. 2003, 18, 142–148. [Google Scholar] [CrossRef] [PubMed]
- Pinho, G.L.L.; Moura da Rosa, C.; Maciel, F.E.; Bianchini, A.; Yunes, J.S.; Proenca, L.A.O.; Monserrat, J.M. Antioxidant responses after microcystin exposure in gills of an estuarine crab species pre-treated with vitamin E. Ecotoxicol. Environ. Saf. 2005, 61, 361–365. [Google Scholar] [CrossRef] [PubMed]
- Prieto, A.I.; Jos, A.; Pichardo, S.; Moreno, I.; Cameán, A.M. Protective role of vitamin E on the Microcystin induced oxidative stress in Tilapia fish (Oreochromis sp.). Environ. Toxicol. Chem. 2008, 27, 1152–1159. [Google Scholar] [CrossRef] [PubMed]
- Prieto, A.I.; Jos, A.; Pichardo, S.; Moreno, I.M.; Alvarez de Sotomayor, M.; Moyano, R.; Blanco, A.; Camean, A.M. Time-dependent protective efficacy of Trolox (vitamin E analog) against microcystin induced toxicity in Tilapia (Oreochromis niloticus). Environ. Toxicol. 2009, 54, 563–579. [Google Scholar] [CrossRef] [PubMed]
- Al-Jassabi, S.; Khalil, A.M. Microcystin-induced 8-hydroxydeoxyguanosine in DNA and its reduction by melatonin, vitamin C and vitamin E in mice. Biochemistry 2006, 71, 1115–1119. [Google Scholar] [CrossRef] [PubMed]
- Weng, D.; Lu, Y.; Wei, Y.; Liu, Y.; Shen, P. The role of ROS in microcystin-LR-induced hepatocyte apoptosis and liver injury in mice. Toxicology 2007, 232, 15–23. [Google Scholar] [CrossRef] [PubMed]
- Ruebhart, D.-R.; Wickramasinghe, W.; Cock, I.E. Protective efficacy of the antioxidants Vitamin E and Trolox against Microcystis aeruginosa and Microcystin-LR in Artemia franciscana Nauplii. J. Toxicol. Environ. Health 2009, 72, 1567–1575. [Google Scholar] [CrossRef] [PubMed]
- Bulc Rozman, K.; Juric, D.M.; Šuput, D. Selective cytotoxicity of microcystins LR, LW and LF in rat astrocytes. Toxicol. Lett. 2017, 265, 1–8. [Google Scholar] [CrossRef] [PubMed]
- Eriksson, J.E.; Grönberg, L.; Nygård, S.; Slotte, J.P.; Meriluoto, J.A.O. Hepatocellular uptake of 3H-dihydromicrocystin-LR, a cyclic peptide toxin. Biochim. Biophys. Acta 1990, 1025, 60–66. [Google Scholar] [CrossRef]
- Hagenbuch, B.; Meier, P.J. The superfamily of organic anion transporting polypeptides. Biochim. Biophys. Acta 2003, 1609, 1–18. [Google Scholar] [CrossRef]
- Hagenbuch, B.; Meier, P.J. Organic anion transporting polypeptides of the OATP/ SLC21 family: Phylogenetic classification as OATP/SLCO superfamily, new nomenclature and molecular/functional properties. Pflügers Arch. 2004, 447, 653–665. [Google Scholar] [CrossRef] [PubMed]
- Fischer, A.; Hoeger, S.J.; Stemmer, K.; Feurstein, D.J.; Knobeloch, D.; Nussler, A.; Dietrich, D.R. The role of organic anion transporting polypeptides (OATPs/SLCOs) in the toxicity of different microcystin congeners in vitro: A comparison of primary human hepatocytes and OATP-transfected HEK293 cells. Toxicol. Appl. Pharmacol. 2010, 245, 9–20. [Google Scholar] [CrossRef] [PubMed]
- Konig, J.; Seithel, A.; Gradhand, U.; Fromm, M.F. Pharmacogenomics of human OATP transporters. Naunyn Schmiedebergs Arch. Pharmacol. 2006, 372, 432–443. [Google Scholar] [CrossRef] [PubMed]
- Hilgendorf, C.; Ahlin, G.; Seithel, A.; Artursson, P.; Ungell, A.L.; Karlsson, J. Expression of thirty-six drug transporter genes in human intestine, liver, kidney, and organotypic cell lines. Drug Metab. Dispos. 2007, 35, 1333–1340. [Google Scholar] [CrossRef] [PubMed]
- Oostendorp, R.L.; Beijnen, J.H.; Schellens, J.H. The biological and clinical role of drug transporters at the intestinal barrier. Cancer Treat. Rev. 2009, 35, 137–147. [Google Scholar] [CrossRef] [PubMed]
- Satoh, H.; Yamashita, F.; Tsujimoto, M.; Murakami, H.; Koyabu, N.; Ohtani, H.; Sawada, Y. Citrus juices inhibit the function of human organic anion-transporting polypeptide OATP-B. Drug Metab. Dispos. 2005, 33, 518–523. [Google Scholar] [CrossRef] [PubMed]
- Naseem, S.M.; Hines, H.B.; Creasia, D.A. Inhibition of microcystin-induced release of cyclooxygenase products from rat hepatocytes by anti-inflammatory steroids. Proc. Soc. Exp. Biol. Med. 1990, 195, 345–349. [Google Scholar] [CrossRef] [PubMed]
- Samuni, Y.; Golstein, S.; Dean, O.M.; Berk, M. The chemistry and biological activities of N-acetylcysteine. Biochim. Biophys. Acta 2013, 1830, 4117–4129. [Google Scholar] [CrossRef] [PubMed]
- Bonanomi, L.; Gazzaniga, A. Toxicological, pharmacokinetic and metabolic studies on acetylcysteine. Eur. J. Respir. Dis. Suppl. 1980, 111, 45–51. [Google Scholar] [PubMed]
- Atkuri, K.R.; Mantovani, J.J.; Herzenberg, L.A.; Herzenberg, L.A. N-acetylcysteine—A safe antidote for cysteine/glutathione deficiency. Curr. Opin. Pharmacol. 2007, 7, 355–359. [Google Scholar] [CrossRef] [PubMed]
- Rushworth, G.F.; Megson, I.L. Existing and potential therapeutic uses for N-acetylcysteine: The need for conversion to intracellular glutathione for antioxidant benefits. Pharmacol. Ther. 2014, 141, 150–159. [Google Scholar] [CrossRef] [PubMed]
- Halliwell, B. Vitamin C: Antioxidant or pro-oxidant in vivo. Free Radic. Res. 1996, 25, 439–454. [Google Scholar] [CrossRef] [PubMed]
- Sevgiler, Y.; Piner, P.; Durmaz, H.; Üner, N. Effects of N-acetylcysteine on oxidative responses in the liver of fenthion exposed Cyprinus carpio. Pest. Biochem. Physiol. 2007, 87, 248–254. [Google Scholar] [CrossRef]
- Sprong, R.C.; Winkelhuyzen-Janssen, A.M.L.; Aarsman, C.J.M.; van Oirschot, J.F.L.M.; van der Bruggen, T.; van Asbeck, B.S. Low-dose N-acetylcysteine protects rats against endotoxin-mediated oxidative stress, but high-dose increases mortality. Am. J. Respir. Crit. Care Med. 1998, 157, 1283–1293. [Google Scholar] [CrossRef] [PubMed]
- Peña-Llopis, S.; Ferrando, M.D.; Peña, J.B. Fish tolerance to organophosphate induced oxidative stress is dependent on the glutathione metabolism and enhanced by N-acetylcysteine. Aquat. Toxicol. 2003, 65, 337–360. [Google Scholar] [CrossRef]
- Wang, X.; Zuo, Z.; Zhao, C.; Zhang, Z.; Peng, G.; Cao, S.; Hu, Y.; Yu, S.; Zhong, Z.; Deng, J.; et al. Protective role of selenium in the activities of antioxidant enzymes in piglet splenic lymphocytes exposed to deoxynivalenol. Environ. Toxicol. Pharmacol. 2016, 47, 53–61. [Google Scholar] [CrossRef] [PubMed]
- Batcioglu, K.; Ozturk, I.C.; Karagozler, A.A.; Karatas, F. Comparison of selenium level with GSH-Px activity in the liver of mice treated 7,12-DMBA. Cell Biochem. Funct. 2002, 20, 115–118. [Google Scholar] [CrossRef] [PubMed]
- Rotruck, J.T.; Pope, A.L.; Ganther, H.E.; Swanson, A.B.; Hafeman, D.G.; Hoekstra, W.G. Selenium: Biochemical role as a component of glutathione peroxidase. Science 1973, 179, 588–590. [Google Scholar] [CrossRef] [PubMed]
- Kelly, S.A.; Havrilla, C.M.; Brady, T.C.; Abramo, K.H.; Levin, E.D. Oxidative stress in toxicology: Established mammalian and emerging piscine model systems. Environ. Health Perspect. 1998, 106, 375–384. [Google Scholar] [CrossRef] [PubMed]
- Hoffmann, P.R. Mechanisms by which selenium influences immune responses. Arch. Immunol. Ther. Exp. 2007, 55, 289–297. [Google Scholar] [CrossRef]
- Maggini, S.; Wintergerst, E.S.; Beveridge, S.; Hornig, D.H. Selected vitamins and trace elements support immune function by strengthening epithelial barriers and cellular and humoral immune responses. Br. J. Nutr. 2007, 98, S29–S35. [Google Scholar] [CrossRef] [PubMed]
- Zeng, H. Selenium as an essential micronutrient: Roles in cell cycle and apoptosis. Molecules 2009, 14, 1263–1278. [Google Scholar] [CrossRef] [PubMed]
- Spallholz, J.E.; Palace, V.P.; Reid, T.W. Methioninase and selenomethionine but not Se-methylselenocysteine generate methylselenol and superoxide in an in vitro chemiluminescent assay: Implications for the nutritional carcinostatic activity of selenoamino acids. Biochem. Pharmacol. 2004, 67, 547–554. [Google Scholar] [CrossRef] [PubMed]
- Peuthert, A.; Pflugmacher, S. Influence of the cyanotoxin microcystin-LR on tocopherol in Alfalfa seedlings (Medicago sativa). Toxicon 2010, 56, 411–417. [Google Scholar] [CrossRef] [PubMed]
- Van Acker, S.A.B.E.; Koymans, L.M.H.; Bast, A. Molecular pharmacology of vitamin E: Structural aspects of antioxidant activity. Free Radic. Biol. Med. 1993, 15, 311–328. [Google Scholar] [CrossRef]
- Traber, M.; Atkinson, J. Vitamin E, antioxidant and nothing more. Free Radic. Biol. Med. 2007, 43, 4–15. [Google Scholar] [CrossRef] [PubMed]
- Pekmezci, D. Vitamins and the Immunity. In Vitamins & Hormones; Zoe Kruze: Kurupelit, Turkey, 2011; pp. 179–215. [Google Scholar]
- Galli, F.; Azzi, A.; Birringer, M.; Cook-Mills, J.M.; Eggersdorfer, M.; Frank, J.; Cruciani, G.; Lorkowski, S.; Özer, N.K. Vitamin E: Emerging aspects and new directions. Free Radic. Biol. Med. 2017, 102, 16–36. [Google Scholar] [CrossRef] [PubMed]
- Mitchel, R.E.J.; McCann, R.A. Skin tumor promotion by Vitamin E in mice: Amplification by ionizing radiation and Vitamin C. Cancer Detect. Prev. 2003, 27, 102–108. [Google Scholar] [CrossRef]
- Tafazoli, S.; Wright, J.S.; O’Brien, P.J. Prooxidant and antioxidant activity of vitamin E analogues and troglitazone. Chem. Res. Toxicol. 2005, 18, 1567–1574. [Google Scholar] [CrossRef] [PubMed]
- Naidu, K.A. Vitamin C in human health and disease is still a mystery? An overview. Nutr. J. 2003, 2, 7. [Google Scholar] [CrossRef] [PubMed]
- Ohno, S.; Ohno, Y.; Suzuki, N.; Soma, G.; Inoue, M. High-dose vitamin C (ascorbic acid) therapy in the treatment of patients with advanced cancer. Anticancer Res. 2009, 29, 809–815. [Google Scholar] [PubMed]
- Bendich, A.; D’Apolito, P.; Gabriel, E.; Machlin, L.J. Interaction of dietary vitamin C and vitamin E on guinea pig immune responses to mitogens. J. Nutr. 1984, 114, 1588–1593. [Google Scholar] [PubMed]
- Igarashi, O.; Yonekawa, Y.; Fujiyama-Fujihara, Y. Synergistic action of vitamin E and vitamin C in vivo using a new mutant of Wistar-strain rats, ODS, unable to synthesize vitamin C. J. Nutr. Sci. Vitaminol. 1991, 37, 359–369. [Google Scholar] [CrossRef] [PubMed]
- Sastre, J.; Pallardo, F.V.; Vina, J. Mitochondrial oxidative stress plays a key role in aging and apoptosis. IUBMB Life 2000, 49, 427–435. [Google Scholar] [CrossRef] [PubMed]
- Mukherjee, D.; Ghosh, A.K.; Dutta, M.; Mitra, E.; Mallick, S.; Saha, B.; Reiter, R.J.; Bandyopadhyay, D. Mechanisms of isoproterenol-induced cardiac mitochondrial damage: Protective actions of melatonin. J. Pineal Res. 2015, 58, 275–290. [Google Scholar] [CrossRef] [PubMed]
- Asghari, M.H.; Abdollahi, M.; de Oliveira, M.R.; Nabavi, S.M. A review of the protective role of melatonin during phosphine-induced cardiotoxicity: focus on mitochondrial dysfunction, oxidative stress and apoptosis. J. Pharm. Pharmacol. 2016, 69, 236–243. [Google Scholar] [CrossRef] [PubMed]
- Reiter, R.J.; Tan, D.X.; Mayo, J.C.; Sainz, R.M.; Leon, J.; Czarnocki, Z. Melatonin as an antioxidant: Biochemical mechanisms and pathophysiological implications in humans. Acta Biochim. Pol. 2003, 50, 1129–1146. [Google Scholar] [PubMed]
- Da Silva, C.M.; Macías-García, B.; Miró-Morán, A.; González-Fernández, L.; Morillo-Rodriguez, A.; Ortega-Ferrusola, C.; Gallardo-Bolaños, J.M.; Stilwell, G.; Tapia, J.A.; Peña, F.J. Melatonin reduces lipid peroxidation and apoptotic-like changes in stallion spermatozoa. J. Pineal Res. 2011, 51, 172–179. [Google Scholar] [CrossRef] [PubMed]
- Sánchez, A.; Calpena, A.C.; Clares, B. Evaluating the oxidative stress in inflammation: Role of melatonin. Int. J. Mol. Sci. 2015, 16, 16981–17004. [Google Scholar] [CrossRef] [PubMed]
- Cook, N.C.; Samman, S. Flavonoids—Chemistry, metabolism, cardioprotective effects and dietary sources. J Nutr. Biochem. 1996, 7, 66–76. [Google Scholar] [CrossRef]
- Middleton, E.; Kandaswamy, C.; Theoharides, T.C. The effects of plant flavonoids on mammalian cells: Implications for inflammation, heart disease and cancer. Pharmacol. Rev. 2000, 52, 673–751. [Google Scholar] [PubMed]
- Pandey, K.B.; Rizvi, S.I. Plant polyphenols as dietary antioxidants in human health and disease. Oxid. Med. Cell. Longev. 2009, 2, 270–278. [Google Scholar] [CrossRef] [PubMed]
- Cao, J.; Han, J.; Xiao, H.; Qiao, J.; Han, M. Effect of Tea Polyphenol Compounds on Anticancer Drugs in Terms of Anti-Tumor Activity, Toxicology, and Pharmacokinetics. Nutrients 2016, 8, 762. [Google Scholar] [CrossRef] [PubMed]
- Schroeder, P.; Klotz, L.O.; Sies, H. Amphiphilic properties of (−)-epicatechin and their significance of protection of cells against peroxynitrite. Biochem. Biophys. Res. Commun. 2003, 307, 69–73. [Google Scholar] [CrossRef]
- Sarma, D.N.; Barrett, M.L.; Chavez, M.L.; Gardiner, P.; Ko, R.; Mahady, G.B.; Marles, R.J.; Pellicore, L.S.; Giancaspro, G.I.; Low Dog, T. Safety of green tea extracts: A systematic review by the US Pharmacopeia. Drug Saf. 2008, 31, 469–484. [Google Scholar] [CrossRef] [PubMed]
- Shi, J.; Zhou, J.; Zhang, M. Microcystins induces vascular inflammation in human umbilical vein endothelial cells via activation of NF-kappaB. Mediat. Inflamm. 2015, 2015, 1–7. [Google Scholar] [CrossRef]
- Cornblatt, B.S.; Ye, L.X.; Dinkova-Kostova, A.T.; Erb, M.; Fahey, J.W.; Singh, N.K.; Chen, M.A.; Stierer, T.; Garrett-Mayer, E.; Argani, P.; et al. Preclinical and clinical evaluation of sulforaphane for chemoprevention in the breast. Carcinogenesis 2007, 28, 1485–1490. [Google Scholar] [CrossRef] [PubMed]
- Lin, W.; Wu, R.T.; Wu, T.Y.; Khor, T.O.; Wang, H.; Kong, A.N. Sulforaphane suppressed LPS-induced inflammation in mouse peritoneal macrophages through Nrf2 dependent pathway. Biochem. Pharmacol. 2008, 76, 967–973. [Google Scholar] [CrossRef] [PubMed]
- Talalay, P.; Fahey, J.W.; Healy, Z.R.; Wehage, S.L.; Benedict, A.L.; Min, C.; Dinkova-Kostova, A.T. Sulforaphane mobilizes cellular defenses that protect skin against damage by UV radiation. Proc. Natl. Acad. Sci. USA 2007, 104, 17500–17505. [Google Scholar] [CrossRef] [PubMed]
- Gan, N.Q.; Sun, X.Y.; Song, L.R. Activation of Nrf2 by microcystin-LR provides advantages for liver cancer cell growth. Chem. Res. Toxicol. 2010, 23, 1477–1484. [Google Scholar] [CrossRef] [PubMed]
- Fu, J.; Xie, P. The acute effects of microcystin LR on the transcription of nine glutathione S-transferase genes in common carp Cyprinus carpio L. Aquat. Toxicol. 2006, 80, 261–266. [Google Scholar] [CrossRef] [PubMed]
- Lee, J.-S.; Surh, Y.J. Nrf2 as a novel molecular target for chemoprevention. Cancer Lett. 2005, 224, 171–184. [Google Scholar] [CrossRef] [PubMed]
- Monserrat, J.M.; Lima, J.V.; Ferreira, J.L.R.; Acosta, D.; Garcia, M.L.; Ramos, P.B.; Moraes, T.B.; Dos Santos, L.C.; Amado, L.L. Modulation of antioxidant and detoxification responses mediated by lipoic acid in the fish Corydoras paleatus (Callychthyidae). Comp. Biochem. Physiol. 2008, 148, 287–292. [Google Scholar] [CrossRef]
- Packer, L.; Tritschler, H.J.; Wessel, K. Neuroprotection by the metabolic antioxidant—Lipoic acid. Free Radic. Biol. Med. 1997, 22, 359–378. [Google Scholar] [CrossRef]
- Bilska, A.; Wlodek, L. Lipoic acid—The drug of the future? Pharmacol. Rep. 2005, 57, 570–577. [Google Scholar] [PubMed]
- Ohtani, I.; Moore, R.E.; Runnegar, M.T. Cylindrospermopsin: A potent hepatotoxin from the blue-green algae Cylindrospermopsis raciborskii. J. Am. Chem. Soc. 1992, 114, 7941–7942. [Google Scholar] [CrossRef]
- Runnegar, M.T.; Xie, C.; Snider, B.B.; Wallace, G.A.; Weinreb, S.M.; Kuhlenkamp, J. In vitro hepatotoxicity of the cyanobacterial alkaloid cylindrospermopsin and related synthetic analogues. Toxicol. Sci. 2002, 67, 81–87. [Google Scholar] [CrossRef] [PubMed]
- Runnegar, M.T.; Kong, S.M.; Zhong, Y.Z.; Ge, J.L.; Lu, S.C. The role of glutathione in the toxicity of a novel cyanobacterial alkaloid cylindrospermopsin in cultured rat hepatocytes. Biochem. Biophys. Res. Commun. 1994, 201, 235–241. [Google Scholar] [CrossRef] [PubMed]
- Puerto, M.; Pichardo, S.; Jos, A.; Gutiérrez-Praena, D.; Cameán, A.M. Acute effects of pure Cylindrospermopsin on the activity and transcription of antioxidant enzymes in Tilapia (Oreochromis niloticus) exposed by gavage. Ecotoxicology 2011, 20, 1852–1860. [Google Scholar] [CrossRef] [PubMed]
- Gutierrez-Praena, D.; Pichardo, S.; Jos, A.; Moreno, F.J.; Cameán, A.M. Biochemical and pathological toxic effects induced by the cyanotoxin Cylindrospermopsin on the human cell line Caco-2. Water Res. 2012, 46, 1566–1575. [Google Scholar] [CrossRef] [PubMed]
- Falconer, I.R.; Humpage, A.R. Cyanobacterial (Blue-Green Algal) toxins in water supplies: Cylindrospermopsins. Environ. Toxicol. 2006, 21, 299–304. [Google Scholar] [CrossRef] [PubMed]
- Fessard, V.; Bernard, C. Cell alterations but no DNA strand breaks induced in vitro by cylindrospermopsin in CHO K1 cells. Environ. Toxicol. 2003, 18, 353–359. [Google Scholar] [CrossRef] [PubMed]
- Bain, P.; Shaw, G.; Patel, B. Induction of p53-regulated gene expression in human cell lines exposed to the cyanobacterial toxin cylindrospermopsin. J. Toxicol. Environ. Health Part A 2007, 70, 1687–1693. [Google Scholar] [CrossRef] [PubMed]
- Froscio, S.M.; Fanok, S.; Humpage, A.R. Cytotoxicity screening for the cyanobacterial toxin Cylindrospermopsin. J. Toxicol. Environ. Health Part A 2009, 72, 345–349. [Google Scholar] [CrossRef] [PubMed]
- Froscio, S.M.; Cannon, E.; Lau, H.M.; Humpage, A.R. Limited uptake of the cyanobacterial toxin cylindrospermopsin by Vero cells. Toxicon 2009, 54, 862–868. [Google Scholar] [CrossRef] [PubMed]
- Chong, M.W.; Wong, B.S.; Lam, P.K.; Shaw, G.R.; Seawright, A.A. Toxicity and uptake mechanism of cylindrospermopsin and lophyrotomin in primary rat hepatocytes. Toxicon 2002, 40, 205–211. [Google Scholar] [CrossRef]
- Fernández, D.A.; Louzao, M.C.; Vilariño, N.; Fraga, M.; Espiña, B.; Vieytes, M.R.; Botana, L.M. Evaluation of the intestinal permeability and cytotoxic effects of cylindrospermopsin. Toxicon 2014, 91, 23–34. [Google Scholar] [CrossRef] [PubMed]
- Pichardo, S.; Devesa, V.; Puerto, M.; Vélez, D.; Cameán, A.M. Intestinal transport of Cylindrospermopsin using the Caco-2 cell line. Toxicol. In Vitro 2017, 38, 142–149. [Google Scholar] [CrossRef] [PubMed]
- Gutiérrez-Praena, D.; Puerto, M.; Prieto, A.I.; Jos, A.; Pichardo, S.; Vasconcelos, V.M.; Cameán, A.M. Protective role of dietary N-acetylcysteine on the oxidative stress induced by cylindrospermopsin in tilapia (Oreochromis niloticus). Environ. Toxicol. Chem. 2012, 31, 1548–1555. [Google Scholar] [CrossRef] [PubMed]
- Gutiérrez-Praena, D.; Risalde, M.A.; Pichardo, S.; Jos, A.; Moyano, R.; Blanco, A.; Vasconcelos, V.; Cameán, A.M. Histopathological and immunohistochemical analysis of Tilapia (Oreochromis niloticus) exposed to cylindrospermopsin and the effectiveness of N-Acetylcysteine to prevent its toxic effects. Toxicon 2014, 78, 18–34. [Google Scholar] [CrossRef] [PubMed]
- Guzmán-Guillén, R.; Prieto, A.I.; Vázquez, C.M.; Vasconcelos, V.; Cameán, A.M. The protective role of l-carnitine against cylindrospermopsin-induced oxidative stress in tilapia (Oreochromis niloticus). Aquat. Toxicol. 2013, 132–133, 141–150. [Google Scholar] [CrossRef] [PubMed]
- Guzmán-Guillén, R.; Prieto Ortega, A.I.; Martín-Caméan, A.; Cameán, A.M. Beneficial effects of Vitamin E supplementation against the oxidative stress on Cylindrospermopsin-exposed tilapia (Oreochromis niloticus). Toxicon 2015, 104, 34–42. [Google Scholar] [CrossRef] [PubMed]
- Guzmán-Guillén, R.; Prieto Ortega, A.I.; Gutiérrez-Praena, D.; Moreno, I.M.; Moyano, R.; Blanco, A.; Cameán, A.M. Vitamin E pretreatment prevents histopathological effects in tilapia (Oreochromis niloticus) acutely exposed to cylindrospermopsin. Environ. Toxicol. 2016, 31, 1469–1485. [Google Scholar] [CrossRef] [PubMed]
- Guzmán-Guillén, R.; Prieto Ortega, A.I.; Moyano, R.; Blanco, A.; Vasconcelos, V.; Cameán, A.M. Dietary l-carnitine prevents histopathological changes in tilapia (Oreochromis niloticus) exposed to cylindrospermopsin. Environ. Toxicol. 2017, 32, 241–254. [Google Scholar] [CrossRef] [PubMed]
- López-Alonso, H.; Rubiolo, J.A.; Vega, F.; Vieytes, M.R.; Botana, L.M. Protein synthesis inhibition and oxidative stress induced by cylindrospermopsin elicit apoptosis in primary rat hepatocytes. Chem. Res. Toxicol. 2013, 26, 203–212. [Google Scholar] [CrossRef] [PubMed]
- Fenning, A.; Pringle, R.; Vella, R.; Smith, H. Prevention of Cylindrospermopsin-induced hepatic, renal and cardiovascular damage via novel antioxidant treatments. J. Mol. Cell. Cardiol. 2006, 41, 732–751. [Google Scholar] [CrossRef]
- Arrigo, A.P. Gene expression and the thiol redox state. Free Radic. Biol. Med. 1999, 27, 936–944. [Google Scholar] [CrossRef]
- Sies, H. Glutathione and its role in cellular functions. Free Radic. Biol. Med. 1999, 27, 916–921. [Google Scholar] [CrossRef]
- Rebouche, C.J. Ascorbic acid and carnitine biosynthesis. Am. J. Clin. Nutr. 1991, 54, 1147S–1152S. [Google Scholar] [PubMed]
- Flanagan, J.L.; Simmons, P.A.; Vehige, J.; Willcox, M.D.; Garrett, Q. Role of carnitine in disease. Nutr. Metab. 2010, 7, 30–44. [Google Scholar] [CrossRef] [PubMed]
- Bueno, R.; Alvarez, M.; Perez-Guerrero, C.; Gomez-Amores, L.; Vazquez, C.M.; Herrera, M.D. L-carnitine and propionyl-L-carnitine improve endothelial dysfunction in spontaneously hypertensive rats: Different participation of NO and COX-products. Life Sci. 2005, 77, 2082–2097. [Google Scholar] [CrossRef] [PubMed]
- Harpaz, S. L-Carnitine and its attributed functions in fish culture and nutrition—A review. Aquaculture 2005, 249, 3–21. [Google Scholar] [CrossRef]
- Broderick, T.L. ATP production and TCA activity are stimulated by propionyl-L-carnitine in the diabetic rat heart. Drugs R D 2008, 9, 83–91. [Google Scholar] [CrossRef] [PubMed]
- Lee, B.J.; Lin, J.S.; Lin, Y.C.; Lin, P.T. Effects of L-carnitine supplementation on lipid profiles in patients with coronary artery disease. Lipids Health Dis. 2016, 15, 107. [Google Scholar] [CrossRef] [PubMed]
- Derin, N.; Izgut-Uysal, V.N.; Agac, A.; Aliciguzel, Y.; Demir, N. L-carnitine protects gastric mucosa by decreasing ischemia-reperfusion induced lipid peroxidation. J. Physiol. Pharmacol. 2004, 55, 595–606. [Google Scholar] [PubMed]
- Gómez-Amores, L.; Mate, A.; Miguel-Carrasco, J.L.; Jiménez, L.; Jos, A.; Cameán, A.M.; Revilla, E.; Santa-María, C.; Vázquez, C.M. L-Carnitine attenuates oxidative stress in hypertensive rats. J. Nutr. Biochem. 2007, 18, 533–540. [Google Scholar] [CrossRef] [PubMed]
- Ribas, G.S.; Vargas, C.R.; Wajner, M. L-carnitine supplementation as a potential antioxidant therapy for inherited neurometabolic disorders. Gene 2014, 533, 469–476. [Google Scholar] [CrossRef] [PubMed]
- Kolodziejczyk, J.; Saluk-Juszczak, J.; Wachowicz, B. L-Carnitine protects plasma components against oxidative alterations. Nutrition 2011, 27, 693–699. [Google Scholar] [CrossRef] [PubMed]
- Tousson, E.; Hafez, E.; Zaki, S.; Gad, A. The cardioprotective effects of L-carnitine on rat cardiac injury, apoptosis, and oxidative stress caused by amethopterin. Environ. Sci. Pollut. Res. 2016, 23, 20600–20608. [Google Scholar] [CrossRef] [PubMed]
- Wang, Q.; Ju, X.; Chen, Y.; Dong, X.; Luo, S.; Liu, H.; Zhang, D. Effects of L-carnitine against H2O2-induced oxidative stress in grass carp ovary cells (Ctenopharyngodon idellus). Fish Physiol. Biochem. 2016, 42, 845–857. [Google Scholar] [CrossRef] [PubMed]
- Palmieri, F. Diseases caused by defects of mitochondrial carriers: A review. Biochim. Biophys. Acta 2008, 1777, 564–578. [Google Scholar] [CrossRef] [PubMed]
- Xue, Y.Z.; Wang, L.X.; Liu, H.Z.; Qi, X.W.; Wang, X.H.; Ren, H.Z. L-carnitine as an adjunct therapy to percutaneous coronary intervention for non-ST elevation myocardial infarction. Cardiovasc. Drugs Ther. 2007, 21, 445–448. [Google Scholar] [CrossRef] [PubMed]
- Zambrano, S.; Blanca, A.J.; Ruiz-Armenta, M.V.; Miguel-Carrasco, J.L.; Revilla, E.; Santa-Maria, C.; Mate, A.; Vázquez, C.M. The renoprotective effect of L-carnitine in hypertensive rats is mediated by modulation of oxidative stress-related gene expression. Eur. J. Nutr. 2013, 52, 1649–1659. [Google Scholar] [CrossRef] [PubMed]
- Blanca, A.J.; Ruiz-Armenta, M.V.; Zambrano, S.; Salsoso, R.; Miguel-Carrasco, J.L.; Fortuño, A.; Revilla, E.; Mate, A.; Vázquez, C.M. Leptin Induces Oxidative Stress Through Activation of NADPH Oxidase in Renal Tubular Cells: Antioxidant Effect of L-Carnitine. J. Cell Biochem. 2016, 117, 2281–2288. [Google Scholar] [CrossRef] [PubMed]
- Shakeri, A.; Tabibi, H.; Heayati, M. Effects of L-carnitine supplement on serum inflammatory cytokines, C-reactive protein, lipoprotein (a), and oxidative stress in hemodialysis patients with Lp (a) hyperlipoproteinemia. Hemodial. Int. 2010, 14, 498–504. [Google Scholar] [CrossRef] [PubMed]
- Moeinian, M.; Ghasemi-Niri, S.F.; Mozaffari, S.; Abdollahi, M. Synergistic effect of probiotics, butyrate and L-Carnitine in treatment of IBD. JMHI 2013, 7, 50–53. [Google Scholar] [CrossRef]
- Hseu, Y.C.; Lo, H.W.; Korivi, M.; Tsai, Y.C.; Tang, M.J.; Yang, H.L. Dermato-protective properties of ergothioneine through induction of Nrf2/ARE-mediated antioxidant genes in UVA-irradiated Human Keratinocytes. Free Radic. Biol. Med. 2015, 86, 102–117. [Google Scholar] [CrossRef] [PubMed]
- Oyang, Y.; Chen, Z.W.; Tan, M.; Liu, A.M.; Chen, M.H.; Liu, J.; Pi, R.B.; Fang, J.P. Carvedilol, a third-generation β-blocker prevents oxidative stress-induced neuronal death and activates Nrf2/ARE pathway in HT22 cells. Biochem. Biophys. Res. Commun. 2013, 441, 917–922. [Google Scholar] [CrossRef] [PubMed]
- Oyanagi, E.; Yano, H.; Uchida, M.; Utsumi, K.; Sasaki, J. Protective action of L-carnitine on cardiac mitochondrial function and structure against fatty acid stress. Biochem. Biophys. Res. Commun. 2011, 412, 61–67. [Google Scholar] [CrossRef] [PubMed]
- Santulli, A.; D’Amelio, V. Effects of supplemental dietary carnitine on the growth and lipid metabolism of hatchery-reared sea bass (Dicentrarchus labrax L.). Aquaculture 1986, 59, 177–186. [Google Scholar] [CrossRef]
- Torreele, E.; Van der Sluizen, A.; Verreth, J. The effect of dietary L-carnitine on the growth performance in fingerlings of the African catfish Clarias gariepinus.in relation to dietary lipid. Br. J Nutr. 1993, 69, 289–299. [Google Scholar] [CrossRef] [PubMed]
- Yang, D.S.; Liu, F.G.; Liou, C.H. Effects of dietary L-carnitine, plant proteins and lipid levels on growth performance, body composition, blood traits and muscular carnitine status in juvenile silver perch (Bidyanus bidyanus). Aquaculture 2012, 342, 48–55. [Google Scholar] [CrossRef]
- Jayaprakas, V.; Sambhu, C.; Sunil Kumar, S. Effect of dietary L-carnitine on growth and reproductive performance of male Oreochromis mossambicus (Peters). Fish Technol. 1996, 33, 84–90. [Google Scholar] [CrossRef]
- Schlechtriem, C.; Bresler, V.; Fishelson, L.; Rosenfeld, M.; Becker, K. Protective effects of dietary l-carnitine on tilapia hybrids (Oreochromis niloticus x Oreochromis aureus) reared under intensive pond-culture conditions. Aquac. Nutr. 2004, 10, 55–63. [Google Scholar] [CrossRef]
- Liu, L.; Zhang, D.M.; Wang, M.X.; Fan, C.Y.; Zhou, F.; Wang, S.J.; Kong, L.D. The adverse effects of long-term L-carnitine supplementation on liver and kidney function in rats. Hum. Exp. Toxicol. 2015, 34, 1148–1161. [Google Scholar] [CrossRef] [PubMed]
- Muthuswamy, A.D.; Vedagiri, K.; Ganesan, M.; Chinnakannu, P. Oxidative stress-mediated macromolecular damage and dwindle in antioxidant status in aged rat brain regions: Role of L-carnitine and DL-alpha-lipoic acid. Clin. Chim. Acta 2006, 368, 84–92. [Google Scholar] [CrossRef] [PubMed]
- Canbaz, H.; Akca, T.; Tataroglu, C.; Caglikulekci, M.; Dirlik, M.; Ayaz, L.; Ustunsoy, A.B.; Tasdelen, B.; Aydin, S. The Effects of Exogenous L-Carnitine on Lipid Peroxidation and Tissue Damage in an Experimental Warm Hepatic Ischemia-Reperfusion Injury Model. Curr. Ther. Res. Clin. Exp. 2007, 68, 32–46. [Google Scholar] [CrossRef] [PubMed]
- Shekhawat, P.S.; Srinivas, S.R.; Matern, D.; Bennett, M.J.; Boriack, R.; George, V.; Xu, H.; Prasad, P.D.; Roon, P.; Ganapathy, V. Spontaneous development of intestinal and colonic atrophy and inflammation in the carnitine-deficient jvs (OCTN2-/-) mice. Mol. Genet. Metab. 2007, 92, 315–324. [Google Scholar] [CrossRef] [PubMed]
- De Marchi, S.; Zecchetto, S.; Rigoni, A.; Prior, M.; Fondrieschi, L.; Scuro, A.; Rulfo, F.; Arosio, E. Propionyl-l-carnitine improves endothelial function, microcirculation and pain management in critical limb ischemia. Cardiovasc. Drugs Ther. 2012, 26, 401–408. [Google Scholar] [CrossRef] [PubMed]
- Dayanand, C.D.; Krishnamurthy, N.; Ashakiran, S.; Shashidhar, K.N. Carnitine: A novel health factor—An overview. Int. J. Pharm. Biomed. Res. 2011, 2, 79–89. [Google Scholar]
- Pearson, P.; Lewis, S.A.; Britton, J.; Young, I.S.; Fogarty, A. The pro-oxidant activity of high-dose vitamin E supplements in vivo. Biodrugs 2006, 20, 271–273. [Google Scholar] [CrossRef] [PubMed]
- Moghaddas, A.; Dashti-Khavidaki, S. Potential protective effects of L-carnitine against neuromuscular ischemia-reperfusion injury: From experimental data to potential clinical applications. Clin. Nutr. 2016, 35, 783–790. [Google Scholar] [CrossRef] [PubMed]
Chemoprotectant | Experimental Model Used | Doses/Concentration of MCs | Dose of Chemoprotectant | Effect of Chemoprotectant | References |
---|---|---|---|---|---|
N-acetylcysteine (NAC) | Primary rat hepatocytes | 120 µg/mL from a microcystic cyanobacteria extract | NAC: 10 mM | Cells pretreated for 6 h showed reduced cytotoxicity and enhanced the intracellular GSH level. | [37] |
NAC | Mouse | 100 µg/kg | NAC: 15 mg/kg | NAC: 1 h pretreatment extended survival time; at 3 and 24 h pretreatment 25% of the animals survived. Coadministration was not effective. | [33] |
L-cysteine (Cys) | Amifostine: 226 mg/kg | L-Cys: only at 24 h pretreatment extended survival time. | |||
Amifostine | L-Cys: 280 mg/kg | Amifostine: No protection though a slight increase in survival time was observed. | |||
Glutathione (GSH) | GSH: 2000 mg/kg | GSH: only at 3 h pretreatment protected 25% of the mice, and coadministration protected 50%. | |||
NAC | Tilapia (Oreochromis niloticus) | 120 µg MC-LR/fish | 20, 44, or 96.8 mg NAC/fish /day, pretreatment during 7 days | NAC reduced hepatic and renal oxidative stress induced by MCs, recovering LPO, GSH levels, and increased antioxidant enzyme activities, mainly by the lower dose. The highest dose induced alterations in SOD, GPx, and GR activities. | [39] |
NAC | Tilapia (O. niloticus) | 120 µg MC-LR/fish | 20, 44, or 96.8 mg NAC/fish /day, pretreatment during 7 days | Prevention of histopathological changes in a dose-dependent way (20–44 mg/NAC/fish/day) in the liver, kidney, heart, gastrointestinal tract, and gills | [40] |
NAC | CHO cells | 0, 2.5, 5, and 10 µg MC-LR/mL | 0, 1, and 5 nmol/L | NAC has a protective effect by increasing cell viability, decreasing ROS, elevating MMP, and reducing apoptosis index. | [41] |
Cys | Mouse | 10 mM MC-LR | L-Cys: 10 mM | MC-LR in Cys solution did not cause acute liver toxicity. However, MC-LR in GSH solution showed weaker acute toxicity of MC-LR than intact MC-LR. | [42] |
GSH | GSH: 10 mM | ||||
Cyclosporin A (CyA) | Mouse | 100 µg/kg | CyA: 10 mg/kg | CyA: Pretreatment for 1 and 3 h showed 100% protection and extended survival time. Coadministration gave 100% protection, and post-treatment could not prevent lethality. | [33] |
Naringin | Naringin: 50 mg/kg | Naringin: protected 25% of the animals after 1 h pretreatment, and at 3 and 24 h pretreatment only survival time was marginally extended. | |||
Rifampicin | Rifampicin: 25mg/kg | Rifampicin: pretreatment 1 h completely protected all the mice. Coadministration gave 100% protection. Post-administration 15 and 30 min 75% of the animals were protected. | |||
Silymarin | Silymarin: 400 mg/kg | Silymarin: protected 75% after 1 h pretreatment and 100% protection after 3 and 24 h. | |||
CyA | Mouse | 100 μg/kg (MC-LR) i.p. | 100 mg/kg | Prevented lethality when given 0.5–3 h prior to MC-LR | [35] |
CyA | Mouse | 1.7–1.8 × LD50 MC (MC-LR, -RR, -LY, -LA) | 0.2 mg/mouse | Prevented 90% lethality when given up to 1 min after MC-LR administration. After 5 min no protection was observed. | [43] |
Cytochalasins (Cyt) | Primary cultures of rat hepatocytes | 1 μg/mL (MC-LR) | Cyt: 10 μM | Cyt and bile acids showed negative effects when administered alone to cells. Higher protective effect of Rif was observed in hepatocytes treated with lower concentrations than bile acids. | [44] |
Rifampicin (Rif) | Rif: 2 μM | ||||
Bile acids (cholic acid and deocycholate) | Bile acids: 0.1 mM | ||||
Trypan blue (TB) | TB: 20 μM | ||||
Trypan red (TR) | TR: 20 μM | ||||
CyA | Isolated rat hepatocytes | 320 mM MC-YM | CyA: 5 μM | Decreased accumulation of MC-YM after 30 min of exposure was observed when cells were pretreated for 1 min with chemoprotectant. The reductions observed were 37% for CyA, 26% for Rif, 30% for TB, and 66% for TR. | [45] |
Rifampicin | Rif: 50 μM | ||||
TB | TB: 20 μM | ||||
TR | TR: 20 μM | ||||
CyA | Mouse | 100 μg/kg MC-LR | CyA: 10 mg/kg | Pretreatment with all substances provided 100% protection against lethality. However, some of the toxic effects of MC-LR (such as GSH depletion, lipid peroxidation and protein phosphatase inhibition) were observed in surviving animals up to 7 days after exposure but normalized after 14 days. | [46] |
Rifampicin | Rif: 25 mg/kg | ||||
Silymarin | Sy: 400 mg/kg | ||||
Epigallocatechin-3-gallate | HUVECs | 40 µM MC-LR | 0–50 µM | EGCG reversed oxidant effects by reducing ROS and increasing SOD and GSH levels, and reduced NF-ĸB in cells. Moreover, it suppressed MC-LR-induced expression of ICAM-1 and VCAM-1, associated with inflammatory processes. | [47] |
Flavonoids: quercetin, silybin, morin | Mouse | 0.75 LD50 MC-LR: 57.5 µg/kg | Quercetin: 200 mg/kg Silybin: 400 mg/kg Morin: 400 mg/kg | The levels of the hepatic enzymes ALT, AST, and LDH were reversed to control at 3 days post-exposure. At 3 days, the PPAse activity was reversed to control values in all the flavonoid-treated groups | [48] |
D-glucose | Mouse | 100 µg/kg | D-glucose: 2000 mg/kg | D-glucose pretreatment increased survival time, but showed no protection from lethality. Mannitol and DHA had no protective effect at all the pretreatment time points, although mannitol extended survival time. Trolox ® at 24 h pretreatment protected 25% of the animals. Only Trolox coadministered with MC-LR significantly extended survival time but it could not prevent lethality. | [33] |
Mannitol | Mannitol: 2000 mg/kg | ||||
Dihydroxy-acetone | Dihydroxy-acetone: 50 mg/kg | ||||
Trolox | Trolox: 10 mg/kg | ||||
Lipoic acid | Common carp (Cyprinus carpio, Cyprinidae) | 50 µg MC/kg i.p. | 40 mg/kg i.p. | Co-exposure led to an increase in GST activity in brain and reverted GST inhibition in liver. | [49] |
Lipopolysaccharide | Artemia salina Daphnia magna, Daphnia galeata | A. salina: 2 µg/mL MC-LR D. magna: 1.26 µg/mL MC-LR D. galeata: 0.003 µg/mL MC-LR | 2 ng/mL | Pre-incubation and simultaneous addition of LPS and MC-LR protected from lethal toxicity of MC-LR. The protective effect of LPS is mediated by detoxication enzyme pathways. | [50] |
Naringin | Isolated rat hepatocytes | 0.3–1 µM MC-LR | 100 μM | Naringin prevented phosphorylation and disruption of the cytoskeleton caused by MC-LR. Moreover, dose-dependent apoptosis induced by MC-LR was suppressed by naringin. | [51] |
Naringin | Freshwater snail (Sinotaia histrica) | 13.7 mg/g D.W. MC-LR | 1–10 mM | One single exposure to 1 mM naringin prevented 60% of MC-LR uptake in hepatopancreas. The uptake prevention rate was 100% when snails were continuously treated with 10 mM naringin for 8 days. | [52] |
Naringin | HEK293-OATP1B3 cells | 1–200 µM MC-LR | 5-500 µM | Cytotoxicity of MC-LR was attenuated by naringin in a dose-dependent manner as the uptake of MC-LR into HEK293-OATP1B3 cells was inhibited by naringin. | [53] |
Nostocyclopeptide-M1 (Ncp-1M) | Isolated rat hepatocytes, HEK293-OATP1B3, OATP1B1, OATP2B1 | 50 nM [125I]-MC-YR | 10-20 µM | Ncp-1M inhibits the human MC-carrying transporters OATP1B1 and OATP1B3, blocking MC uptake. | [54] |
Polyphenols (Green tea, GTP) | Mouse | 10 μg/kg/day (MC-LR) i.p. | 50, 100 and 200 μg/kg/day | GTP protected by elevating in serum antioxidant activities (GSH and SOD), reducing MDA level, inhibiting ROS, hepatocellular apoptosis, and up-regulating Bcl-2 protein expression. Multifocal liver cell degeneration and zonal coagulative necrosis were ameliorated. | [31] |
Se (Sodium selenite) | Mice | 75 ìg /kg MC-LR, i.p. (1 dose) sacrifice at 24 h | 1.5 ìg /mouse/day, i.p. (2 weeks prior to MC-LR) | Partial recovery of histopathological alterations in liver. Increase in GST and GPx enzymatic activities. | [55] |
62 ìg /kg MC-LR, i.p. | |||||
(10 doses) sacrifice at 72 h | 1.5 ìg /mouse/day, i.p. (6 weeks prior to MC-LR) | Recovery of body weight in liver. Partial recovery of ALT levels and glycogen (mg/g). Recovery of TBA values and GST levels. GPx activity increase. | |||
Se (sodium selenite) | Tilapia (O. niloticus) | Cyanobacterial cells containing 120 µg MC-LR/fish, 24 h | Pretreatment with 1.5, 3.0, 6.0 µg Se/g diet during 7 days | Se protection depended on the dose and the biomarker considered. The highest dose of Se could affect some oxidative stress biomarkers. The highest dose ameliorated the histopathological changes in the liver, kidney, heart, and GI tract of fish. | [56] |
κ-Selenocarrageenan (Se-Car) | BALB/c mice | 50 μg/kg MC-LR i.p. | 90 ppb | Se-Car reduced lipid and protein peroxidation induced by MC-LR. Activities of GST and CAT were reduced and induced up-regulation of SOD. It could also abate the toxicity through ER function restoration. | [32] |
Sulforaphane (SFN) | HepG2 BRL-3A NIH 3 T3 | 10 µM of MC-LR | 10 μM | Protective response was mediated though Nrf2 pathway in vitro. | [57] |
SFN | BALB/c mice | 40 and 50 μg/kg MC-LR after 8 h | 5 μmol | SFN activated Nrf2 pathway in vivo and the protection included activities of anti-cytochrome P450 induction, anti-oxidation, anti-inflammation, and anti-apoptosis. | [58] |
Vitamin E | Mice | 100 ìg /kg MC-LR, i.p. | 86, 170, or 340 U i.p. 48 h prior to MC-LR | Prevention of death in 50% of the animals (up to 24 h) (with 170 or 340 U). Prevention of the serum LDH levels increase induced by MC (with 340 U). | [36] |
Vitamin E (α- tocopherol acetate) | Mice | 100 µg/ kg MC-LR extract, i.p. (7 doses) 100 µg/ kg MC-LR extract, i.p. (1 dose) | 8.33 or 33.3 UI/mouse/day for 4 weeks 33.3 or 66.6 mg/mouse/day for 2 weeks | Partial recovery of LPO, ALT, and GST parameters compared to the control levels by reduction of LPO and ALT levels, and GST increased compared to toxin-treated control group (with 33.3 mg) in liver. Reduction of liver damage (with 33.3 and 66.6 mg). Increased time to death (with 66.6 mg) | [59] |
Vitamin E | Estuarine crab (Chasmagnathus granulatus) | 1.21 µg/kg/day MC-LR, oral injection, sacrifice on days 2 and 7 | 600 mg/kg bw/day (41 days) | CAT activity decreased in gills. Recovery of GST activity compared to the control levels. Increase of nonproteic sulfhydryl groups. | [60] |
Vitamin E | Tilapia (O. niloticus) | Cyanobacterial cells containing 120 µg MC-LR/fish, commercial diet, 24 h | Pretreatment with 200 or 700 mg vitamin E/kg diet during 7 days | Vitamin E-pretreated fish showed no alteration in LPO levels, and oxidative enzymatic activities were improved. The highest dose employed gave the greater protective effects. | [61] |
Vitamin E | Tilapia (O. niloticus) | Cyanobacterial cells containing 120 µg MC-LR/fish, with the diet. Fish were sacrificed at 24, 48, or 72 h | Pretreatment with 200 or 700 mg vit E/kg diet during 7 days | The oxidative stress biomarkers were ameliorated, and the higher protection was observed 24 h post toxin exposure. Histopathological lesions were more evidently recovered after 72 h. | [62] |
Vitamin E Vitamin C Melatonin | Mice | 75 ìg /kg MC-LR, i.p. (1 dose) sacrifice at 24 h | Vitamin E: 36.2 µM Vitamin C: 30.4 µM Melatonin: 0.55 µM per mouse/day, for 2 weeks | Recovery of ALT levels: Melatonin > Vitamin E > Vitamin C. Inhibition of 8-OH-dG formation in a dose-dependent manner: Melatonin > Vitamin C ≈ Vitamin E. | [63] |
Vitamin E Vitamin C | Mice | 60 µg/kg MC-LR, i.p., sacrifice at 12 h | 200 and 250 mg/kg bw/day (3 days) | Decrease in ROS and MDA levels. Partial recovery of ALT and AST levels compared to the control levels by reduction of both parameters in liver. Protection against apoptosis and chromatin condensation produced by MC-LR. Prevented decrease in membrane potential. Recovery of Bax and Bid expression up to the control levels in liver. | [64] |
Vitamin E Trolox | Artemia franciscana Nauplii | MC-LR (40 µg/mL) and Microcystis aeruginosa extract (CE, 10 mg dw/mL) | 100 µg/mL antioxidant pretreatment (4 h exposure) | Both antioxidant pretreatments reduced mortality of approximately 50% at 9 h post-exposure against MC-LR, but offered little to no protection from cyanobacterial extract. | [65] |
Chemoprotectant | MCs Dose | Parameters Studied | Effects | Ref. | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Liver | Kidney | |||||||||||
NAC | 120 µg MC-LR/fish, oral, 24 h | 20, 44, or 96.8 mg/fish/day (7 days before intoxication) | 20 mg | 44 mg | 96.8 mg | 20 mg | 44 mg | 96.8 mg | [39,40] | |||
LPO | Total | Total | Total | Partial | Total | Alteration | ||||||
Protein oxidation | No prevention | No prevention | No prevention | - | - | - | ||||||
CAT | Partial | Total | Total | Total | Total | Total | ||||||
SOD | No prevention | No prevention | No prevention | Total | Total | No prevention | ||||||
GR | No prevention | No prevention | No prevention | Total | Total | Alteration | ||||||
GPx | Total | No prevention | No prevention | No prevention | No prevention | Total | ||||||
GST | Total | Total | Total | No MC effect | Alteration | Alteration | ||||||
GSH/GSSG | Total | Total | Total | - | - | - | ||||||
Histopathology | Liver, kidney, heart, intestines, and gills: partial recovery from toxic effects of 20 mg and total from 40 mg. Induction of toxic effect at 96.8 mg. | |||||||||||
Se (sodium selenite) | Cyanobacterial cells 120 µg MC-LR/fish, oral, 24 h | 1.5, 3.0, and 6.0 µg Se/g diet (7 days before intoxication) | Liver | Kidney | [56] | |||||||
1.5 µg | 3.0 µg | 6.0 µg | 1.5 µg | 3.0 µg | 6.0 µg | |||||||
LPO | No prevention | Partial | Total | No prevention | Alteration | Alteration | ||||||
Protein oxidation | Alteration | Alteration | Alteration | Alteration | Alteration | Alteration | ||||||
CAT | Total | Partial | No prevention | No Se effect | Alteration | Alteration | ||||||
SOD | No prevention | No prevention | Total | Total | Total | Total | ||||||
GR | Total | Total | Total | No prevention | No prevention | No prevention | ||||||
GPx | No prevention | Total | Total | No prevention | Partial | Total | ||||||
GST | Partial | Partial | Total | No prevention | No prevention | No prevention | ||||||
GSH/GSSG | Alteration | Alteration | Alteration | - | - | - | ||||||
Histopathology | Liver: Partial (1.5 µg) and Total (3.0 and 6.0 µg) Kidney: No Se effect (1.5 µg), Partial (3.0 µg) and Total (6.0µg) Heart: Partial (1.5 and 3.0 µg) and Total (6.0 µg) Intestines: Partial (1.5 and 3.0 µg) and Total (6.0 µg) | |||||||||||
Vitamin E | Cyanobacterial cells 120 µg MC-LR/fish, oral, 24 h | 200 or 700 mg vitamin E/kg diet (7 days before intoxication) | Liver | Kidney | Gills | [61] | ||||||
200 mg | 700 mg | 200 mg | 700 mg | 200 mg | 700 mg | |||||||
LPO | Total | Total | Partial | Total | No MC effect | No MC effect | ||||||
Protein oxidation | No MC effect | No MC effect | - | - | - | - | ||||||
CAT | No prevention | Total | No prevention | Total | No prevention | Total | ||||||
SOD | Total | Total | Total | Total | Total | Total | ||||||
GR | No MC effect | No MC effect | PT | PT | No MC effect | No MC effect | ||||||
GPx | Alteration | Alteration | No prevention | No prevention | No prevention | No prevention | ||||||
Vitamin E (Trolox) | Cyanobacterial cells 120 µg MC-LR/fish, oral, 24, 48, or 72 h | 700 mg vitamin E/kg diet (7 days before intoxication) | Liver | Kidney | Gills | [62] | ||||||
24 h | 48 h | 72 h | 24 h | 48 h | 72 h | 24 h | 48 h | 72 h | ||||
LPO | Partial | No prevention | No prevention | Partial | Total | Total | Partial | Partial | No prevention | |||
Protein oxidation | No prevention | No MC effect | No MC effect | - | - | - | - | - | - | |||
CAT | Partial | Partial | No MC effect | Alteration | No prevention | No prevention | No MC effect | Partial | No MC effect | |||
SOD | Total | Partial | No prevention | No prevention | No prevention | No prevention | No MC effect | Total | Partial | |||
GPx | Partial | Partial | No prevention | Partial | No prevention | No prevention | Partial | No MC effect | No MC effect | |||
GR | Partial | Partial | No MC effect | Partial | No MC effect | Partial | No MC effect | No MC effect | No MC effect | |||
GST | Partial | Partial | No prevention | No prevention | No MC effect | No prevention | No MC effect | No MC effect | No MC effect | |||
GSH/GSSG | Total | No MC effect | No MC effect | No MC effect | No MC effect | No MC effect | No MC effect | No MC effect | No MC effect | |||
Histopathology | Liver: Partial (24 h) and Total (72 h) Kidney: Partial (24 h and 72 h) Heart: Partial (24 h) and Total (72 h) Intestines: Total (24 h and 72 h) Gills: Total (24 h and 72 h) |
Chemoprotectant | CYN Dose | Parameters Studied | Effects | References | |||
---|---|---|---|---|---|---|---|
NAC | 200 µg/kg bw (pure and from an extract of A. ovalisporum) | 22, 45 (mg/fish/day) 7 days | Liver | Kidney | [138,139] | ||
22 | 45 | 22 | 45 | ||||
LPO | Total | Total | Partial | Partial | |||
Protein oxidation | No CYN effect | No CYN effect | Total | Total | |||
GST | Total | Total | No CYN effect | No CYN effect | |||
GPx | Total | Total | No CYN effect | No CYN effect | |||
γ-GCS | Partial | Partial | Total | Total | |||
GSH/GSSG | Total | Total | Total | Total | |||
GST gene expression | Increased | Increased | Reduced | Reduced | |||
GPx gene expression | Increased | Increased | - | - | |||
Histopathology | Liver and heart: partial prevention at 22 mg/fish/day, and total prevention at 45 mg/fish/day | ||||||
Kidney, GI tract, and gills: total prevention at 22 mg/fish/day | |||||||
LC | 400 µg/kg bw (pure and from an extract of A. ovalisporum) | 20, 40 (mg/fish/day) 21 days | Liver | Kidney | [140,143] | ||
20 | 44 | 20 | 44 | ||||
LPO | Total | Total | Total | Total | |||
Protein oxidation | Total | Total | Total | Total | |||
DNA oxidation | Total | Total | Total | Total | |||
NADPH oxidase | Total | Total | No CYN effect | No CYN effect | |||
GST | No CYN effect | No CYN effect | Total | Total | |||
GPx | No prevention | No prevention | No CYN effect | No effect CYN | |||
SOD | No CYN effect | No CYN effect | Partial | Partial | |||
CAT | No CYN effect | No CYN effect | Total | Total | |||
γ-GCS | No CYN effect | No CYN effect | Total | Total | |||
GSH/GSSG | Total | Total | Total | Total | |||
Histopathology | Liver, kidney, GI tract, and gills: total prevention at 20 mg/fish/day | ||||||
Heart: no prevention at 20 mg/fish/day, and total prevention at 44 mg/fish/day | |||||||
Morphometry | Liver and heart: No CYN effect | ||||||
Kidney: total prevention at 20 mg/fish/day | |||||||
Vitamin E | 400 µg/kg bw (pure) | 25 (mg/fish/day) 7 days | Liver | Kidney | [141,142] | ||
25 | 25 | ||||||
LPO | Total | Total | |||||
Protein oxidation | Total | No CYN effect | |||||
DNA oxidation | No CYN effect | No CYN effect | |||||
GST | Total | Total | |||||
GPx | Total | No CYN effect | |||||
SOD | Total | No prevention | |||||
CAT | Total | Total | |||||
γ-GCS | Total | No CYN effect | |||||
GSH/GSSG | Total | No CYN effect | |||||
Histopathology | Liver, kidney, GI tract, gills, and brain: total prevention | ||||||
Heart: partial prevention | |||||||
Morphometry | Liver, kidney, and heart: total prevention |
© 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Guzmán-Guillén, R.; Puerto, M.; Gutiérrez-Praena, D.; Prieto, A.I.; Pichardo, S.; Jos, Á.; Campos, A.; Vasconcelos, V.; Cameán, A.M. Potential Use of Chemoprotectants against the Toxic Effects of Cyanotoxins: A Review. Toxins 2017, 9, 175. https://doi.org/10.3390/toxins9060175
Guzmán-Guillén R, Puerto M, Gutiérrez-Praena D, Prieto AI, Pichardo S, Jos Á, Campos A, Vasconcelos V, Cameán AM. Potential Use of Chemoprotectants against the Toxic Effects of Cyanotoxins: A Review. Toxins. 2017; 9(6):175. https://doi.org/10.3390/toxins9060175
Chicago/Turabian StyleGuzmán-Guillén, Remedios, María Puerto, Daniel Gutiérrez-Praena, Ana I. Prieto, Silvia Pichardo, Ángeles Jos, Alexandre Campos, Vitor Vasconcelos, and Ana M. Cameán. 2017. "Potential Use of Chemoprotectants against the Toxic Effects of Cyanotoxins: A Review" Toxins 9, no. 6: 175. https://doi.org/10.3390/toxins9060175