Comparative Effects of Deferiprone and Salinomycin on Lead-Induced Disturbance in the Homeostasis of Intrarenal Essential Elements in Mice
Abstract
:1. Introduction
2. Results
2.1. Effects of Deferiprone and Tetraethylammonium Salt of Salinomycinic Acid (Salinomycin) on the Renal Concentration of Pb in Pb-Exposed Mice
2.2. Histological Analysis
2.3. Effects of Pb, Deferiprone and Salinomycin on Glomeruli Count and Glomeruli Area
2.4. Effects of Pb, Deferiprone and Salinomycin on Biochemical Markers in the Sera of Experimental Mice
2.5. Effects of Pb, Deferiprone and Salinomycin on the Renal Concentrations of Essential Elements
3. Discussion
4. Materials and Methods
4.1. Chemicals and Reagents
4.2. Preparation of Salinomycinic Acid
4.3. Animals
4.4. Experimental Design
4.5. Biochemical Analyses of Sera
4.6. ICP-MS Analysis
4.6.1. Sample Preparation
4.6.2. Measurements
4.7. Histological Analysis
4.8. Morphometric Analysis
4.9. Statistical Data Processing
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Global Burden of Disease Study 2013 Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990–2013: A systematic analysis for the Global Burden of Disease Study 2013. Lancet 2015, 386, 743–800. [Google Scholar] [CrossRef] [Green Version]
- Harari, F.; Sallsten, G.; Christensson, A.; Petkovic, M.; Hedblad, B.; Forsgard, N.; Melander, O.; Nilsson, P.M.; Borné, Y.; Engström, G.; et al. Blood Lead Levels and Decreased Kidney Function in a Population-Based Cohort. Am. J. Kidney Dis. 2018, 72, 381–389. [Google Scholar] [CrossRef] [Green Version]
- Ekong, E.B.; Jaar, B.G.; Weaver, V.M. Lead-related nephrotoxicity: A review of the epidemiologic evidence. Kidney Int. 2006, 70, 2074–2084. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lin, J.L.; Lin-Tan, D.T.; Hsu, K.H.; Yu, C.C. Environmental lead exposure and progression of chronic renal diseases in patients without diabetes. N. Engl. J. Med. 2003, 348, 277–286. [Google Scholar] [CrossRef] [PubMed]
- Mabrouk, A. Thymoquinone attenuates lead-induced nephropathy in rats. J. Biochem. Mol. Toxicol. 2018, 33, e22238. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Imafidon, C.E.; Akomolafe, R.O.; Eluwole, O.A.; Adekunle, I.A.; Agbaje, R.A. Aqueous garlic extract improves renal clearance via vasodilatory/antioxidant mechanisms and mitigated proteinuria via stabilization of glomerular filtration barrier. Clin. Phytosci. 2019, 5, 27. [Google Scholar] [CrossRef] [Green Version]
- Yu, Y.; Yu, L.; Zhou, X.; Qiao, N.; Qu, D.; Tian, F.; Zhao, J.; Zhang, H.; Zhai, Q.; Chen, W. Effects of acute oral lead exposure on the levels of essential elements of mice: A metallomics and dose-dependent study. J. Trace Elem. Med. Biol. 2020, 62, 126624. [Google Scholar] [CrossRef]
- Mabrouk, A.; Cheikh, H.B. Thymoquinone ameliorates lead-induced suppression of the antioxidant system in rat kidneys. Libyan J. Med. 2016, 11, 31018. [Google Scholar] [CrossRef]
- Wang, L.; Zhou, X.; Yang, D.; Wang, Z. Effects of lead and/or cadmium on the distribution patterns of some essential trace elements in immature female rats. Hum. Exp. Toxicol. 2011, 30, 1914–1923. [Google Scholar] [CrossRef]
- Aaseth, J.; Skaug, M.A.; Cao, Y.; Andersen, O. Chelation in metal intoxication—Principles and paradigms. J. Trace Elem. Med. Biol. 2015, 31, 260–266. [Google Scholar] [CrossRef]
- Flora, S.J.; Pachauri, V. Chelation in metal intoxication. Int. J. Environ. Res. Public Health 2010, 7, 2745–2788. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bjørklund, G.; Mutter, J.; Aaseth, J. Metal chelators and neurotoxicity: Lead, mercury, and arsenic. Arch. Toxicol. 2017, 91, 3787–3797. [Google Scholar] [CrossRef] [PubMed]
- Hamidinia, S.A.; Erdahl, W.L.; Chapman, C.J.; Steinbaugh, G.E.; Taylor, R.W.; Pfeiffer, D.R. Monensin improves the effectiveness of meso-dimercaptosuccinate when used to treat lead intoxication in rats. Environ. Health Perspect. 2006, 114, 484–493. [Google Scholar] [CrossRef] [Green Version]
- Pachauri, V.; Dubey, M.; Yadav, A.; Kushwaha, P.; Flora, S.J. Monensin potentiates lead chelation efficacy of MiADMSA in rat brain post chronic lead exposure. Food Chem. Toxicol. 2012, 50, 4449–4460. [Google Scholar] [CrossRef] [PubMed]
- Ivanova, J.; Gluhcheva, Y.; Dimova, D.; Pavlova, E.; Arpadjan, S. Comparative assessment of the effects of salinomycin and monensin on the biodistribution of lead and some essential metal ions in mice, subjected to subacute lead intoxication. J. Trace Elem. Med. Biol. 2016, 33, 31–36. [Google Scholar] [CrossRef] [PubMed]
- Ivanova, J.; Kamenova, K.; Petrova, E.; Vladov, I.; Gluhcheva, Y.; Dorkov, P. Comparative study on the effects of salinomycin, monensin and meso-2,3-dimercaptosuccinic acid on the concentrations of lead, calcium, copper, iron and zinc in lungs and heart in lead-exposed mice. J. Trace Elem. Med. Biol. 2020, 58, 126429. [Google Scholar] [CrossRef]
- Kotyzová, D.; Eybl, V.; Koutenský, J.; Míčová, V. Effect of deferiprone on lead-induced oxidative damage and trace elements in rats. Vojen. Zdr. Listy. Supplementum. 2001, LXX, 96–100. [Google Scholar]
- Balooch, F.D.; Fatemi, S.J.; Iranmanesh, M. Combined chelation of lead (II) by deferasirox and deferiprone in rats as biological model. Biometals 2014, 27, 89–95. [Google Scholar] [CrossRef]
- Aslani, M.R.; Azad, M.; Mohriq, M.; Nadjarnezhad, V. Therapeutic effects of pomegranate (Punicagranatum L.) pith and carpellary membrane extract on lead-induced toxicity in rats. Iran. J. Vet. Sci. Technol. 2014, 6, 1–10. [Google Scholar]
- Reckziegel, P.; Dias, V.T.; Benvegnú, D.M.; Boufleur, N.; Barcelos, R.C.S.; Segat, H.J.; Pase, C.S.; Dos Santos, C.M.M.; Flores, É.M.M.; Bürger, M.E. Antioxidant protection of gallic acid against toxicity induced by Pb in blood, liver and kidney of rats. Toxicol. Rep. 2016, 3, 351–356. [Google Scholar] [CrossRef] [Green Version]
- Andjelkovic, M.; Djordjevic, A.B.; Antonijevic, E.; Antonijevic, B.; Stanic, M.; Kotur-Stevuljevic, J.; Spasojevic-Kalimanovska, V.; Jovanovic, M.; Boricic, N.; Wallace, D.; et al. Toxic Effect of Acute Cadmium and Lead Exposure in Rat Blood, Liver, and Kidney. Int. J. Environ. Res. Public Health 2019, 16, 274. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhai, Q.; Qu, D.; Feng, S.; Yu, Y.; Yu, L.; Tian, F.; Zhao, J.; Zhang, H.; Chen, W. Oral Supplementation of Lead-Intolerant Intestinal Microbes Protects Against Lead (Pb) Toxicity in Mice. Front. Microbiol. 2020, 22, 3161. [Google Scholar] [CrossRef] [PubMed]
- Garcia, J.J.D.; Arceo, E. Renal damage associated with heavy metals: Review work. Rev. Colomb. Nefrol. 2018, 5, 43–53. [Google Scholar]
- Ibrahim, N.M.; Eweis, E.A.; El-Beltagi, H.S.; Abdel-Mobdy, Y.E. Effect of lead acetate toxicity on experimental male albino rat. Asian Pac. J. Trop Biomed. 2012, 2, 41–46. [Google Scholar] [CrossRef] [Green Version]
- Offor, S.J.; Mbagwu, H.O.; Orisakwe, O.E. Lead Induced Hepato-renal Damage in Male Albino Rats and Effects of Activated Charcoal. Front. Pharmacol. 2017, 8, 107. [Google Scholar] [CrossRef]
- Wang, H.; Li, D.; Hu, Z.; Zhao, S.; Zheng, Z.; Li, W. Protective Effects of Green Tea Polyphenol Against Renal Injury Through ROS-Mediated JNK-MAPK Pathway in Lead Exposed Rats. Mol. Cells. 2016, 39, 508–513. [Google Scholar] [CrossRef] [Green Version]
- Soussi, A.; Gargouri, M.; Akrouti, A.; El Feki, A. Antioxidant and nephro-protective effect of Juglans regia vegetable oil against lead-induced nephrotoxicity in rats and its characterization by GC-MS. EXCLI J. 2018, 17, 492–504. [Google Scholar] [CrossRef]
- Ezejiofor, A.N.; Orisakwe, O.E. Nephroprotective effect of Costusafer on lead induced kidney damage in albino rats. Int. J. Physiol. Pathophysiol. Pharmacol. 2019, 11, 36–44. [Google Scholar]
- Shafiekhani, M.; Ommati, M.M.; Azarpira, N.; Heidari, R.; Salarian, A.A. Glycine supplementation mitigates lead-induced renal injury in mice. J. Exp. Pharmacol. 2019, 11, 15–22. [Google Scholar] [CrossRef] [Green Version]
- Sasaki, Y.; Iwama, R.; Sato, T.; Heishima, K.; Shimamura, S.; Ichijo, T.; Satoh, H.; Furuhama, K. Estimation of glomerular filtration rate in conscious mice using a simplified equation. Physiol. Rep. 2014, 2, e12135. [Google Scholar] [CrossRef] [Green Version]
- Missoun, F.; Slimani, M.; Aoues, A. Toxic effect of lead on kidney function in rat Wistar. Afr. J. Biochem. Res. 2010, 4, 21–27. [Google Scholar]
- Kittah, N.E.; Vella, A. Management of endocrine desease: Pathogenesis and management of hypoglycemia. Eur. J. Endocrinol. 2017, 177, R37–R47. [Google Scholar] [CrossRef] [PubMed]
- Fowler, B.A.; Kimmel, C.A.; Woods, J.S. Chronic low-level lead toxicity in the rat: III. An integrated assessment of long-term toxicity with special reference to the kidney. Toxicol. Appl. Pharmacol. 1980, 56, 59–77. [Google Scholar] [CrossRef]
- Mehde, A.A.; Yusof, F.; Mezal, S.A.; Farhan, L.O.; Mehdi, W.A. Study the Effect of increased levels of lead on Sera Alpha Amylase Activity, and Some Biochemical Parameters from a Large Private Electrical Generators Iraqi Workers. Adv. Environ. Biol. 2015, 9, 163–167. [Google Scholar]
- Bindu, C.M.; Vidya Shankar, P.; Shetty, H.V.; Gupta, D. Serum amylase in patients with chronic kidney disease. Int. J. Curr. Res. Rev. 2013, 17, 10–15. [Google Scholar]
- Heidari, Z.; Mahmoudzadeh Sagheb, H.R.; Dezfoulian, A.R.; Barbarestani, M.; Noori, S.M.H. A stereological analysis of renal glomeruli following chronic Lead intoxication in rat during a continuous period of 8 weeks. Acta Med. Iran. 2002, 40, 73–78. [Google Scholar]
- Ivanova, J.; Pantcheva, I.N.; Mitewa, M.; Simova, S.; Tanabe, M.; Osakada, K. Cd(II) and Pb(II) complexes of the polyether ionophorous antibiotic salinomycin. Chem. Cent. J. 2011, 5, 52. [Google Scholar] [CrossRef] [Green Version]
- Seely, J.C.; Brixq, A. NTP Neoplastic Lesion Atlas. Kidney, Renal Tubule-Dilation. Available online: https://ntp.niehs.nih.gov/nnl/urinary/kidney/rtdilat/gallery/index.htm (accessed on 1 November 2021).
- da Silva, R.M.; Ko, G.M.; Silva, R.F.; Vieira, L.C.; Vicente de Paula, R.; Marumo, J.T.; Ikegami, A.; Bellini, M.H. Essential elements as biomarkers of acute kidney Injury and spontaneous reversion. Biol. Trace Elem. Res. 2018, 182, 303–308. [Google Scholar] [CrossRef]
- Vormann, J. Magnesium and Kidney Health—More on the ‘Forgotten Electrolyte’. Am. J. Nephrol. 2016, 44, 379–380. [Google Scholar] [CrossRef]
- Dobrakowski, M.; Boron, M.; Birner, E.; Kasperczyk, A.; Chwalińska, E.; Lisowska, G.; Kasperczyk, S. The effect of a short-term exposure to lead on the levels of essential metal ions, selected proteins related to them, and oxidative stress parameters in Humans. Oxidative Med. Cell. Longev. 2017, 2017, 8763793. [Google Scholar] [CrossRef]
- Ilatovskaya, D.V.; Blass, G.; Palygin, O.; Levchenko, V.; Pavlov, T.S.; Grzybowski, M.N.; Winsor, K.; Shuyskiy, L.S.; Geurts, A.M.; Cowley, A.W.; et al. NOX4/TRPC6 Pathway in Podocyte Calcium Regulation and Renal Damage in Diabetic Kidney Disease. J. Am. Soc. Nephrol. 2018, 29, 1917–1927. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pantcheva, I.; Petkov, N.; Simova, S.; Zhorova, R.; Dorkov, P. Alkaline-Earth metal(II) complexes of salinomycin—Spectral properties and antibacterial activity. Phys. Sci. Rev. 2022. [Google Scholar] [CrossRef]
- Ivanova, J.; Pantcheva, I.N.; Zhorova, R.; Momekov, G.; Simova, S.; Stoyanova, R.; Zhecheva, E.; Ivanova, S.; Mitewa, M. Synthesis, spectral properties, antibacterial and antitumor activity of salinomycin complexes with Co(II), Ni(II), Cu(II) and Zn(II) transition metal ions. J. Chem. Chem. Eng. 2012, 6, 51–562. [Google Scholar]
- Kilkenny, C.; Browne, W.J.; Cuthill, I.C.; Emerosn, M.; Altman, D.G. Improving bioscience research reporting: The Arrive guidelines for reporting animal research. PLoS Biol. 2010, 8, e1000412. [Google Scholar] [CrossRef] [PubMed]
- Ghorbe, F.; Boujelbene, M.; Makni-Ayadi, F.; Guermazi, F.; Kammoun, A.; Murat, J.; Croute, F.; Soleilhavoup, J.P.; El-Feki, A. Effect of chronic lead exposure on kidney function in male and female rats: Determination of a lead exposure biomarker. Arch. Physiol. Biochem. 2001, 109, 457–463. [Google Scholar] [CrossRef] [PubMed]
- Pavlova, E.; Pashkunova-Martic, I.; Schaier, M.; Petrova, E.; Gluhcheva, Y.; Dorkov, P.; Helbich, T.H.; Keppler, B.; Koellensperger, G.; Ivanova, J. Ameliorative effects of deferiprone and tetraethylammonium salt of salinomycinic acid on lead-induced toxicity in mouse testes. Environ. Sci. Pollut. Res. Int. 2021, 28, 6784–6795. [Google Scholar] [CrossRef]
- Abubakar, K.; Mailafiya, M.M.; Chiroma, S.M.; Danmaigoro, A.; Zyoud, T.Y.T.; Abdul Rahim, E.; Abu Bakar Zakaria, M.Z. Ameliorative effect of curcumin on lead-induced hematological and hepatorenal toxicity in a rat model. J. Biochem. Mol. Toxicol. 2020, 34, e22483. [Google Scholar] [CrossRef]
- Gao, W.; Guo, Y.; Wang, L.; Jiang, Y.; Liu, Z.; Lin, H. Ameliorative and protective effects of fucoidan and sodium alginate against lead-induced oxidative stress in Sprague Dawley rats. Int. J. Biol. Macromol. 2020, 158, 662–669. [Google Scholar] [CrossRef]
- IBM SPSS Statistics for Windows, Version 23.0; IBM Corp.: Armonk, NY, USA, 2015.
Group | Glomeruli Count | Total Glomeruli Area, % | Mean Glomeruli Area, μm2 |
---|---|---|---|
Ctrl | 6.38 ± 3.02 | 0.42 ± 0.19 | 4352.61 ± 1534.34 |
Pb | 12.80 ± 4.15 * | 0.68 ± 0.10 * | 3538.50 ± 1492.86 * |
Pb + Def | 12.67 ± 2.31 * | 1.11 ± 0.22 *,a | 3976.12 ± 1296.89 a |
Pb + Sal | 5.75 ± 0.96 a,b | 0.38 ± 0.08 a,b | 4628.55 ± 1517.84 a,b |
CR, μmol/L | Urea, mmol/L | Glu, mmol/L | α-Amylase, U/L | |
---|---|---|---|---|
Ctrl | 28.02 ± 1.41 | 10.27 ± 1.57 | 14.22 ± 2.94 | 600.00 ± 64.68 |
Pb | 30.50 ± 1.84 * | 12.53 ± 1.93 * | 10.80 ± 3.80 * | 646.56 ± 55.68 |
Pb + Def | 29.32 ± 2.21 | 12.39 ± 1.91 * | 12.32 ± 2.15 * | 634.71 ± 84.07 |
Pb + Sal | 29.06 ± 1.79 | 16.42 ± 2.26 * | 7.10 ± 2.11 * | 608.00 ± 78.87 |
Mg, mg/kg | P, mg/kg | Ca, mg/kg | Fe, mg/kg | Cu, mg/kg | Se, mg/kg | |
---|---|---|---|---|---|---|
Ctrl | 244.85 ± 12.62 | 4373.79 ± 198.38 | 45.16 ± 3.45 | 54.05 ± 9.12 | 5.16 ± 0.46 | 1.58 ± 0.11 |
Pb | 228.78 ± 13.04 | 3845.25 ± 197.67 * | 40.16 ± 1.91 * | 58.34 ± 12.60 | 4.23 ± 0.42 * | 1.27 ± 0.14 * |
Pb + Def | 227.36 ± 13.24 | 3982.15 ± 163.38 * | 47.59 ± 3.39 | 70.28 ± 7.60 | 4.40 ± 0.24 * | 1.41 ± 0.17 |
Pb + Sal | 213.54 ± 9.69 * | 3794.56 ± 176.18 * | 42.49 ± 2.82 | 82.11 ± 17.59 * | 4.20 ± 0.30 * | 1.31 ± 0.12 * |
Mg/Pb | P/Pb | Ca/Pb | Fe/Pb | Cu/Pb | Se/Pb | |
---|---|---|---|---|---|---|
Ctrl | 0.472 | 0.717 | 0.340 | 0.936 * | 0.844 | 0.983 * |
Pb | 0.718 | 0.220 | 0.437 | −0.600 | 0.595 | 0.498 |
Pb + Def | −0.866 * | −0.849 * | 0.303 | 0.565 | −0.720 | −0.056 |
Pb + Sal | 0.009 | 0.072 | −0.659 | 0.228 | 0.408 | 0.107 |
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Gluhcheva, Y.; Pashkunova-Martic, I.; Schaier, M.; Vladov, I.; Stoykova, S.; Petrova, E.; Pavlova, E.; Dorkov, P.; Helbich, T.H.; Keppler, B.; et al. Comparative Effects of Deferiprone and Salinomycin on Lead-Induced Disturbance in the Homeostasis of Intrarenal Essential Elements in Mice. Int. J. Mol. Sci. 2022, 23, 4368. https://doi.org/10.3390/ijms23084368
Gluhcheva Y, Pashkunova-Martic I, Schaier M, Vladov I, Stoykova S, Petrova E, Pavlova E, Dorkov P, Helbich TH, Keppler B, et al. Comparative Effects of Deferiprone and Salinomycin on Lead-Induced Disturbance in the Homeostasis of Intrarenal Essential Elements in Mice. International Journal of Molecular Sciences. 2022; 23(8):4368. https://doi.org/10.3390/ijms23084368
Chicago/Turabian StyleGluhcheva, Yordanka, Irena Pashkunova-Martic, Martin Schaier, Ivelin Vladov, Silviya Stoykova, Emilia Petrova, Ekaterina Pavlova, Peter Dorkov, Thomas H. Helbich, Bernhard Keppler, and et al. 2022. "Comparative Effects of Deferiprone and Salinomycin on Lead-Induced Disturbance in the Homeostasis of Intrarenal Essential Elements in Mice" International Journal of Molecular Sciences 23, no. 8: 4368. https://doi.org/10.3390/ijms23084368