Comparison of Antiplatelet Effects of Phenol Derivatives in Humans
Abstract
:1. Introduction
2. Materials and Methods
2.1. Blood Donors
2.2. Chemicals
2.3. Aggregometry
2.4. Cell Culture
2.5. Cytotoxicity Assays
2.5.1. CellTiter 96® AQueous One Solution Cell Proliferation Assay
2.5.2. Release of Lactate Dehydrogenase (LDH)
2.6. Anticoagulation Assay
2.7. Statistical Analysis
3. Results
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
- Del Rio, D.; Rodriguez-Mateos, A.; Spencer, J.P.E.; Tognolini, M.; Borges, G.; Crozier, A. Dietary (poly)phenolics in human health: Structures, bioavailability, and evidence of protective effects against chronic diseases. Antioxid. Redox Signal. 2013, 18, 1818–1892. [Google Scholar] [CrossRef] [Green Version]
- Keli, S.O.; Hertog, M.G.; Feskens, E.J.; Kromhout, D. Dietary flavonoids, antioxidant vitamins, and incidence of stroke: The Zutphen study. Arch. Intern. Med. 1996, 156, 637–642. [Google Scholar] [CrossRef] [PubMed]
- Kokubo, Y.; Iso, H.; Ishihara, J.; Okada, K.; Inoue, M.; Tsugane, S. Association of dietary intake of soy, beans, and isoflavones with risk of cerebral and myocardial infarctions in Japanese populations: The Japan Public Health Center-based (JPHC) study cohort I. Circulation 2007, 116, 2553–2562. [Google Scholar] [CrossRef] [Green Version]
- Mursu, J.; Voutilainen, S.; Nurmi, T.; Tuomainen, T.P.; Kurl, S.; Salonen, J.T. Flavonoid intake and the risk of ischaemic stroke and CVD mortality in middle-aged Finnish men: The Kuopio Ischaemic Heart Disease Risk Factor Study. Br. J. Nutr. 2008, 100, 890–895. [Google Scholar] [CrossRef] [Green Version]
- Pimpão, R.C.; Ventura, M.R.; Ferreira, R.B.; Williamson, G.; Santos, C.N. Phenolic sulfates as new and highly abundant metabolites in human plasma after ingestion of a mixed berry fruit purée. Br. J. Nutr. 2015, 113, 454–463. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Feliciano, R.P.; Boeres, A.; Massacessi, L.; Istas, G.; Ventura, M.R.; Nunes Dos Santos, C.; Heiss, C.; Rodriguez-Mateos, A. Identification and quantification of novel cranberry-derived plasma and urinary (poly)phenols. Arch. Biochem. Biophys. 2016, 599, 31–41. [Google Scholar] [CrossRef] [PubMed]
- Applová, L.; Karlíčková, J.; Warncke, P.; Macáková, K.; Hrubša, M.; Macháček, M.; Tvrdý, V.; Fischer, D.; Mladěnka, P. 4-Methylcatechol, a Flavonoid Metabolite with Potent Antiplatelet Effects. Mol. Nutr. Food Res. 2019, 63, 1900261. [Google Scholar] [CrossRef] [PubMed]
- Ostertag, L.M.; O’Kennedy, N.; Horgan, G.W.; Kroon, P.A.; Duthie, G.G.; de Roos, B. In vitro anti-platelet effects of simple plant-derived phenolic compounds are only found at high, non-physiological concentrations. Mol. Nutr. Food Res. 2011, 55, 1624–1636. [Google Scholar] [CrossRef]
- Pourová, J.; Najmanová, I.; Vopršalová, M.; Migkos, T.; Pilařová, V.; Applová, L.; Nováková, L.; Mladěnka, P. Two flavonoid metabolites, 3,4-dihydroxyphenylacetic acid and 4-methylcatechol, relax arteries ex vivo and decrease blood pressure in vivo. Vascul. Pharmacol. 2018, 111, 36–43. [Google Scholar] [CrossRef]
- Jiang, X.-L.; Samant, S.; Lesko, L.J.; Schmidt, S. Clinical Pharmacokinetics and Pharmacodynamics of Clopidogrel. Clin. Pharmacokinet. 2015, 54, 147–166. [Google Scholar] [CrossRef] [Green Version]
- Mărginean, A.; Bănescu, C.; Scridon, A.; Dobreanu, M. Anti-platelet Therapy Resistance—Concept, Mechanisms and Platelet Function Tests in Intensive Care Facilities. J. Crit. Care Med. 2016, 2, 6–15. [Google Scholar] [CrossRef] [Green Version]
- De Maria, E.; Borghi, A.; Modonesi, L.; Cappelli, S. Ticagrelor therapy and atrioventricular block: Do we need to worry? World J. Clin. Cases 2017, 5, 178–182. [Google Scholar] [CrossRef] [PubMed]
- Kasmeridis, C.; Apostolakis, S.; Lip, G.Y.H. Aspirin and aspirin resistance in coronary artery disease. Curr. Opin. Pharmacol. 2013, 13, 242–250. [Google Scholar] [CrossRef] [PubMed]
- Alexopoulos, D.; Xanthopoulou, I.; Mylona, P.; Perperis, A.; Panagiotou, A.; Dimitropoulos, G.; Tsigkas, G.; Hahalis, G.; Davlouros, P. Prevalence of contraindications and conditions for precaution for prasugrel administration in a real world acute coronary syndrome population. J. Thromb. Thrombolysis 2011, 32, 328–333. [Google Scholar] [CrossRef] [PubMed]
- Cattaneo, M. Response variability to clopidogrel: Is tailored treatment, based on laboratory testing, the right solution? J. Thromb. Haemost. 2012, 10, 327–336. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chan, C.-P.; Yuan-Soon, H.; Wang, Y.-J.; Lan, W.-H.; Chen, L.-I.; Chen, Y.-J.; Lin, B.-R.; Chang, M.-C.; Jeng, J.-H. Inhibition of cyclooxygenase activity, platelet aggregation and thromboxane B2 production by two environmental toxicants: M- and o-cresol. Toxicology 2005, 208, 95–104. [Google Scholar] [CrossRef] [PubMed]
- Sanders, J.M.; Bucher, J.R.; Peckham, J.C.; Kissling, G.E.; Hejtmancik, M.R.; Chhabra, R.S. Carcinogenesis studies of cresols in rats and mice. Toxicology 2009, 257, 33–39. [Google Scholar] [CrossRef] [Green Version]
- Dietz, D. NTP technical report on the toxicity studies of Cresols (CAS Nos. 95-48-7, 108-39-4, 106-44-5) in F344/N Rats and B6C3F1 Mice (Feed Studies). Toxic. Rep. Ser. 1991, 9, 1–128. [Google Scholar]
- Sirakanyan, S.N.; Hrubša, M.; Spinelli, D.; Dias, P.; Kartsev, V.; Carazo, A.; Hovakimyan, A.A.; Pourová, J.; Hakobyan, E.K.; Karlíčková, J.; et al. Synthesis of 3,3-dimethyl-6-oxopyrano [3, 4-c]pyridines and their antiplatelet and vasodilatory activity. J. Pharm. Pharmacol. 2021. [Google Scholar] [CrossRef]
- Chan, F.K.; Moriwaki, K.; De Rosa, M.J. Detection of necrosis by release of lactate dehydrogenase activity. Methods Mol. Biol. 2013, 979, 65–70. [Google Scholar] [CrossRef] [Green Version]
- De La Cruz, J.P.; Ruiz-Moreno, M.I.; Guerrero, A.; López-Villodres, J.A.; Reyes, J.J.; Espartero, J.L.; Labajos, M.T.; González-Correa, J.A. Role of the catechol group in the antioxidant and neuroprotective effects of virgin olive oil components in rat brain. J. Nutr. Biochem. 2015, 26, 549–555. [Google Scholar] [CrossRef] [PubMed]
- Jiang, Y.; Zhao, D.; Sun, J.; Luo, X.; Li, H.; Sun, X.; Zheng, F. Analysis of antioxidant effect of two tripeptides isolated from fermented grains (Jiupei) and the antioxidative interaction with 4-methylguaiacol, 4-ethylguaiacol, and vanillin. Food Sci. Nutr. 2019, 7, 2391–2403. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Li, R.; Narita, R.; Ouda, R.; Kimura, C.; Nishimura, H.; Yatagai, M.; Fujita, T.; Watanabe, T. Structure-dependent antiviral activity of catechol derivatives in pyroligneous acid against the encephalomycarditis virus. RSC Adv. 2018, 8, 35888–35896. [Google Scholar] [CrossRef] [Green Version]
- Schweigert, N.; Hunziker, R.W.; Escher, B.I.; Eggen, R.I.L. Acute toxicity of (chloro-)catechols and (chloro-)catechol-copper combinations in Escherichia coli corresponds to their membrane toxicity in vitro. Environ. Toxicol. Chem. 2001, 20, 239–247. [Google Scholar] [CrossRef]
- Senger, D.R.; Li, D.; Jaminet, S.-C.; Cao, S. Activation of the Nrf2 Cell Defense Pathway by Ancient Foods: Disease Prevention by Important Molecules and Microbes Lost from the Modern Western Diet. PLoS ONE 2016, 11, e0148042. [Google Scholar] [CrossRef] [PubMed]
- Macáková, K.; Afonso, R.; Saso, L.; Mladěnka, P. The influence of alkaloids on oxidative stress and related signaling pathways. Free Radic. Biol. Med. 2019, 134, 429–444. [Google Scholar] [CrossRef]
- Zhao, D.; Shi, D.; Sun, J.; Li, H.; Zhao, M.; Sun, B. Quantification and cytoprotection by vanillin, 4-methylguaiacol and 4-ethylguaiacol against AAPH-induced abnormal oxidative stress in HepG2 cells. RSC Adv. 2018, 8, 35474–35484. [Google Scholar] [CrossRef] [Green Version]
- Zhao, D.-R.; Jiang, Y.-S.; Sun, J.-Y.; Li, H.-H.; Luo, X.-L.; Zhao, M.-M. Anti-inflammatory Mechanism Involved in 4-Ethylguaiacol-Mediated Inhibition of LPS-Induced Inflammation in THP-1 Cells. J. Agric. Food Chem. 2019, 67, 1230–1243. [Google Scholar] [CrossRef]
- Zhao, D.R.; Jiang, Y.S.; Sun, J.Y.; Li, H.H.; Sun, X.T.; Zhao, M.M. Amelioration of 4-methylguaiacol on LPS-induced inflammation in THP-1 cells through NF-κB/IκBα/AP-1 and Nrf2/HO-1 signaling pathway. J. Funct. Foods 2019, 55, 95–103. [Google Scholar] [CrossRef]
- Bijak, M.; Saluk, J.; Tsirigotis-Maniecka, M.; Komorowska, H.; Wachowicz, B.; Zaczyńska, E.; Czarny, A.; Czechowski, F.; Nowak, P.; Pawlaczyk, I. The influence of conjugates isolated from Matricaria chamomilla L. on platelets activity and cytotoxicity. Int. J. Biol. Macromol. 2013, 61, 218–229. [Google Scholar] [CrossRef]
- Sellers, C.; Markowitz, S. Reevaluating the carcinogenicity of ortho-toluidine: A new conclusion and its implications. Regul. Toxicol. Pharmacol. 1992, 16, 301–317. [Google Scholar] [CrossRef]
- Johnson, J.D.; Ryan, M.J.; Toft, J.D.; Graves, S.W.; Hejtmancik, M.R.; Cunningham, M.L.; Herbert, R.; Abdo, K.M. Two-Year Toxicity and Carcinogenicity Study of Methyleugenol in F344/N Rats and B6C3F1 Mice. J. Agric. Food Chem. 2000, 48, 3620–3632. [Google Scholar] [CrossRef]
- Smith, R.L.; Adams, T.B.; Doull, J.; Feron, V.J.; Goodman, J.I.; Marnett, L.J.; Portoghese, P.S.; Waddell, W.J.; Wagner, B.M.; Rogers, A.E.; et al. Safety assessment of allylalkoxybenzene derivatives used as flavouring substances—methyl eugenol and estragole. Food Chem. Toxicol. 2002, 40, 851–870. [Google Scholar] [CrossRef]
- Hirose, M.; Fukushima, S.; Tanaka, H.; Asakawa, E.; Takahashi, S.; Ito, N. Carcinogenicity of catechol in F344 rats and B6C3F1 mice. Carcinogenesis 1993, 14, 525–529. [Google Scholar] [CrossRef] [PubMed]
- Schweigert, N.; Belkin, S.; Leong-Morgenthaler, P.; Zehnder, A.J.; Eggen, R.I. Combinations of chlorocatechols and heavy metals cause DNA degradation in vitro but must not result in increased mutation rates in vivo. Environ. Mol. Mutagen. 1999, 33, 202–210. [Google Scholar] [CrossRef]
Compound | IC50 (Mean ± SD, μM) |
---|---|
1,2-dimethylcatechol | ≈78 |
2,4-dimethoxytoluene | ≈32 |
2-aminophenol | 6.65 ± 1.06 |
2-methoxy-4-ethylphenol | 1.37 ± 0.28 |
2-methoxy-4-methylphenol | 2.57 ± 2.24 |
3,5-dichlorocatechol | 13.49 ± 1.57 |
3-aminocatechol | 3.82 ± 0.50 |
3-fluorocatechol | 1.74 ± 0.17 |
3-isopropylcatechol | 2.28 ± 0.30 |
3-methoxycatechol | 7.92 ± 0.74 |
3-methylcatechol | 1.61 ± 0.17 |
4,5-dichlorocatechol | 3.35 ± 0.92 |
4-allyl-1,2-dimethylcatechol | ≈61 |
4-aminocatechol | ≈21 |
4-chlorocatechol | 3.66 ± 0.29 |
4-ethylcatechol | 1.29 ± 0.14 |
4-fluorocatechol | 1.82 ± 0.21 |
4-methylcatechol | 2.59 ± 0.17 |
4-nitrocatechol | 13.27 ± 1.57 |
4-tert-butylcatechol | 7.24 ± 3.75 |
o-cresol | 11.97 ± 5.55 |
pyrocatechol | 4.00 ± 0.45 |
Compound | IC25 (Mean ± SD, μM) |
---|---|
2-methoxy-4-ethylphenol | 5.07 ± 4.05 |
2-methoxy-4-methylphenol | 11.54 ± 9.05 |
3-isopropylcatechol | 12.86 ± 21.28 |
3-methylcatechol | 7.15 ± 6.41 |
4,5-dichlorocatechol | 9.86 ± 15.05 |
4-ethylcatechol | 4.61 ± 1.16 |
4-fluorocatechol | 4.72 ± 0.28 |
4-methylcatechol | 2.66 ± 2.21 |
ASA | 26.85 ± 2.25 |
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Hrubša, M.; Alva, R.; Parvin, M.S.; Macáková, K.; Karlíčková, J.; Fadraersada, J.; Konečný, L.; Moravcová, M.; Carazo, A.; Mladěnka, P. Comparison of Antiplatelet Effects of Phenol Derivatives in Humans. Biomolecules 2022, 12, 117. https://doi.org/10.3390/biom12010117
Hrubša M, Alva R, Parvin MS, Macáková K, Karlíčková J, Fadraersada J, Konečný L, Moravcová M, Carazo A, Mladěnka P. Comparison of Antiplatelet Effects of Phenol Derivatives in Humans. Biomolecules. 2022; 12(1):117. https://doi.org/10.3390/biom12010117
Chicago/Turabian StyleHrubša, Marcel, Raúl Alva, Mst Shamima Parvin, Kateřina Macáková, Jana Karlíčková, Jaka Fadraersada, Lukáš Konečný, Monika Moravcová, Alejandro Carazo, and Přemysl Mladěnka. 2022. "Comparison of Antiplatelet Effects of Phenol Derivatives in Humans" Biomolecules 12, no. 1: 117. https://doi.org/10.3390/biom12010117