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Protective effects of thiazolo[3,2-b]-1,2,4-triazoles on ethanol-induced oxidative stress in mouse brain and liver

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Abstract

A series of 3-[1-(4-(2-methylpropyl) phenyl) ethyl]-1,2,4-triazole-5-thione (I) and its bicyclic condensed derivatives 6-benzylidenethiazolo[3,2-b]-1,2,4-triazole-5(6H)-ones (IIa-IIf) were investigated for the prevention of ethanol-induced oxidative stress in liver and brain of mice. Administration of ethanol (0.1 mL/mice, p.o.) resulted in a drop of total thiol groups (T-SH) and non-protein thiol groups (NP-SH), and an increase in thiobarbituric acid reactive substances (TBARS) in both liver and brain tissue of mice (p<0.001). Among the compounds investigated (at a dose of 200 mg/kg, p.o.), I and IId ameliorated the peroxidative injury in these tissues effectively. Compounds IIa, IIc and IIe improved the peroxidative tissue injury only in brain. These findings suggest that certain condensed thiazolo-triazole compounds may contribute to the control of ethanol-induced oxidative stress in an organ selective manner.

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References

  • Allison, M. C., Howatson, A. G., Torrance, C. J., Lee, F. D., and Russel, R. I., Gastrointestinal damage associated with the use of non-steroidal antiinflammatory drugs.New Engl. J. Med., 327, 749–754 (1992).

    Article  PubMed  CAS  Google Scholar 

  • Barbieri, S. S., Eligini, S., Brambilla, M., Tremoli, E., and Colli, S., Reactive oxygen species mediate cyclooxygenase-2 induction during monocyte to macrophage differentiation: critical role of NADPH oxidase.Cardiovasc. Res., 60, 187–197 (2003).

    Article  PubMed  CAS  Google Scholar 

  • Brooks, P. M. and Day, R. O., Non-steroidal antiinflammatory drug-differences and similarities.New Engl. J. Med., 324, 1716–1725 (1991).

    PubMed  CAS  Google Scholar 

  • Dannhardt, G. and Kiefer, W., Cyclooxygenase inhibitors-current status and future prospects.Eur. J. Med. Chem., 36, 109–126 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Jamall, I. S. and Smith, J. C., Effects of cadmium on glutathione peroxidase, superoxide dismutase, and lipid peroxidation in rat heart: a possible mechanism of cadmium cardiotoxicity.Toxicol. Appl. Pharmacol., 80, 33–42 (1985).

    Article  PubMed  CAS  Google Scholar 

  • Kontogiorgis, C. A. and Hadjipavlou-Litina, D. J., Non-steroidal antiinflammatory and anti-allergy agents.Curr. Med. Chem., 9, 89–98 (2002).

    PubMed  CAS  Google Scholar 

  • Logani, M. K., and Davies, R. E., Lipid oxidation biologic effects and antioxidants: A review.Lipids, 15, 485–494 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Mathurin, P., Deng, O.-G, Keshavarzian, A., Choudhary, S., Holmes, E. W., and Tsukamoto, H., Exacerbation of alcoholic liver injury by enteral endotoxin in rats.Hepatology, 32, 1008–1017 (2000).

    Article  PubMed  CAS  Google Scholar 

  • Mitchell, J. A., Akarasereenont, P., Thiemermann, C., Flower, R. J., and Vane, J. R., Selectivity of nonsteroidal antiinflammatory drugs as inhibitors of constitutive and inducible cyclo-oxygenase.P. Natl. Acad. Sci., 90, 11693–11697 (1994).

    Article  Google Scholar 

  • Nanji, A. A., Miao, L., Thomas, P., Rahemtulla, A., Khwaja, S., Zhao, S., Peters, D., Tahan, S. R., and Dannenberg, A. J., Enhanced cyclooxygenase-2 gene expression in alcoholic liver disease in the rat.Gastroenterology, 112, 943–951 (1997).

    Article  PubMed  CAS  Google Scholar 

  • Nanji, A. A., Zakim, D., Rahemtulla, A., Daly, T., Miao, L., Zhao, S., Khwaja, S., Tahan, S. R., and Dannenberg, A. J., Dietary saturated fatty acids down-regulate cyclooxygenase-2 and tumor necrosis factor alfa and reverse fibrosis in alcohol-induced liver disease in the rat.Hepatology, 26, 1538–1545 (1997).

    Article  PubMed  CAS  Google Scholar 

  • Ohkawa, H., Ohishi, N., and Yagi, K., Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction.Anal. Biochem., 95, 351–358 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Omodeo-Sale, F., Gramigna, D., and Campaniello, R., Lipid peroxidation and antioxidant systems in rat brain: Effect of chronic alcohol consumption.Neurochem. Res., 22, 577–582 (1997).

    Article  PubMed  CAS  Google Scholar 

  • Ravinder, J. S., Glutathione: A marker and antioxidant for aging.J. Lab. Clin. Med., 140, 380–381 (2002)

    Article  Google Scholar 

  • Sanchez-Moreno, C., Paniagua, M., Madrid, A., and Martín, A., Protective effect of vitamin C against the ethanol mediated toxic effects on human brain glial cells.J. Nutr. Biochem., 14, 606–613, (2003).

    Article  PubMed  CAS  Google Scholar 

  • Satoh, T., Fukumori, R., and Kitagawa, H., Changes in tissue concentrations of sulfhydryl groups in relation to the metabolism of biogenic aminesin vitro. Life Sci., 19, 1055–1060 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Sedlak, J. and Lindsay, R. H., Estimation of total protein-bound, and non-protein sulfhydryl groups in tissue with Ellman’s Reagent.Anal. Biochem., 25, 192–205 (1968).

    Article  PubMed  CAS  Google Scholar 

  • Seibert, K., Zhang, Y., Leahy, K., Hauser, S., Masferrer, J., Perkins, W., Lee, L., and Isakson, P., Pharmacological and biochemical demonstration of the role of cyclooxygenase 2 in inflammation and pain.P. Natl. Acad. Sci., 91, 12013–12017 (1994).

    Article  CAS  Google Scholar 

  • Shan, X., Aw, T. Y., and Jones, D. P., Glutathione—dependent protection against oxidative injury.Clin. Pharmacol. Ther., 47, 61–71 (1990).

    CAS  Google Scholar 

  • Song, Y., Connor, D. T., Doubleday, R., Sorenson, R. J., Sercel, A. D., Unangst, P. C., Roth, B. D., Gilbertsen, R. B., Chan, K., Schrier, D. J., Guglietta, A., Bomemeier, D. A., and Dyer, R. D., Synthesis, structure-activity relationships, andin vivo evaluations of substituted di-tert-butylphenols as a novel class of potent, selective, and orally active cyclooxygenase-2 inhibitors.1 thiazolone and oxazolone series.J. Med. Chem., 42, 1151–1160 (1999).

    Article  PubMed  CAS  Google Scholar 

  • Tozkoparan, B., Gökhan, N., Aktay, G., Yesilada, E., and Ertan, M., 6-benzylidenethiazolo [3,2-b]-1,2,4-triazole-5(6H)-ones substituted with ibuprofen: synthesis, characterization and evaluation of antiinflammatory activity.Eur. J. Med. Chem., 35, 743–750 (2000).

    Article  PubMed  CAS  Google Scholar 

  • Weber, H. U., Fleming, J. F., and Miquel, J., Thiazolidine-4-carboxylic acid, a physiologic sulfhydryl antioxidant with potential value in geriatric medicine.Arch. Gerontol. Geriat., 1, 299–310 (1982).

    Article  CAS  Google Scholar 

  • Wlodek, L. and Rommelspacher, H., Ethanol-induced changes in the content of thiol compounds and of lipid peroxidation in livers and brains from mice: Protection by thiazolidin derivatives.Alcohol Alcoholism, 29, 649–657 (1994).

    CAS  Google Scholar 

  • Zentella-de-Pina, M., Saldana-Balmori, Y., Hernandez-Tobias, A., and Pina, E., Non-steroidal antiinflammatory drugs lower ethanol-mediated liver increase in lipids and thiobarbituric acid reactive substances.Alcohol Clin. Exp. Res., 17, 1228–1232 (1993).

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Göknur Aktay.

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Aktay, G., Tozkoparan, B. & Ertan, M. Protective effects of thiazolo[3,2-b]-1,2,4-triazoles on ethanol-induced oxidative stress in mouse brain and liver. Arch Pharm Res 28, 438–442 (2005). https://doi.org/10.1007/BF02977673

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  • DOI: https://doi.org/10.1007/BF02977673

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