Archives of Pharmacal Research

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Protective Effects of Thiazolo[3,2-b]-1,2,4-Triazoles on Ethanol­Induced Oxidative Stress in Mouse Brain and Liver

  • Aktay Goknur (Department of Pharmacology, Faculty of Pharmacy, Inonu University) ;
  • Tozkoparan Birsen (Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University) ;
  • Ertan Mevlut (Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University)
  • Published : 2005.04.01
Download PDF
⟨ Previous Next ⟩

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.

Keywords

References

  1. 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) https://doi.org/10.1056/NEJM199209103271101
  2. 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) https://doi.org/10.1016/S0008-6363(03)00365-1
  3. Brooks, P. M. and Day, R. O., Non-steroidal antiinflammatory drug-differences and similarities. New Engl. J. Med., 324, 1716-1725 (1991) https://doi.org/10.1056/NEJM199106133242407
  4. Dannhardt, G. and Kiefer, W., Cyclooxygenase inhibitorscurrent status and future prospects. Eur. J. Med. Chem., 36, 109-126 (2001) https://doi.org/10.1016/S0223-5234(01)01197-7
  5. 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) https://doi.org/10.1016/0041-008X(85)90098-5
  6. Kontogiorgis, C. A. and Hadjipavlou-Litina, D. J., Non-steroidal antiinflammatory and anti-allergy agents. Curr. Med. Chem., 9, 89-98 (2002) https://doi.org/10.2174/0929867023371409
  7. Logani, M. K., and Davies, R. E., Lipid oxidation biologic effects and antioxidants: A review. Lipids, 15, 485-494 (1980) https://doi.org/10.1007/BF02534079
  8. 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) https://doi.org/10.1053/jhep.2000.19621
  9. 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 cyclooxygenase. P. Natl. Acad. Sci., 90, 11693-11697 (1994) https://doi.org/10.1073/pnas.90.24.11693
  10. 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) https://doi.org/10.1053/gast.1997.v112.pm9041257
  11. 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 alcoholinduced liver disease in the rat. Hepatology, 26, 1538-1545 (1997) https://doi.org/10.1002/hep.510260622
  12. Ohkawa, H., Ohishi, N., and Yagi, K., Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal. Biochem., 95, 351-358 (1979) https://doi.org/10.1016/0003-2697(79)90738-3
  13. 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) https://doi.org/10.1023/A:1022418002765
  14. Ravinder, J. S., Glutathione: A marker and antioxidant for aging. J. Lab. Clin. Med., 140, 380-381 (2002) https://doi.org/10.1067/mlc.2002.129505
  15. Sanchez-Moreno, C., Paniagua, M., Madrid, A., and Martin, A., Protective effect of vitamin C against the ethanol mediated toxic effects on human brain glial cells. J. Nutr. Biochem., 14 , 606-613, (2003) https://doi.org/10.1016/j.jnutbio.2003.07.003
  16. Satoh, T., Fukumori, R., and Kitagawa, H., Changes in tissue concentrations of sulfhydryl groups in relation to the metabolism of biogenic amines in vitro. Life Sci., 19, 1055- 1060 (1976) https://doi.org/10.1016/0024-3205(76)90297-6
  17. 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) https://doi.org/10.1016/0003-2697(68)90092-4
  18. 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) https://doi.org/10.1073/pnas.91.25.12013
  19. Shan, X., Aw, T. Y., and Jones, D. P., Glutathione–dependent protection against oxidative injury. Clin. Pharmacol. Ther., 47, 61-71 (1990) https://doi.org/10.1038/clpt.1990.9
  20. 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., Bornemeier, D. A., and Dyer, R. D., Synthesis, structure-activity relationships, and in 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) https://doi.org/10.1021/jm9805081
  21. Tozkoparan, B., Gokhan, 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) https://doi.org/10.1016/S0223-5234(00)00157-4
  22. 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) https://doi.org/10.1016/0167-4943(82)90030-9
  23. 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)
  24. 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) https://doi.org/10.1111/j.1530-0277.1993.tb05234.x