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Pro-Oxidantive Effect of Dehydroepiandrosterone on Indomethacin-Induced Acute Gastritis in Rats

  • Published : 2009.01.31

Abstract

This study examined whether or not a pretreatment with dehydroepiandrosterone (DHEA) has an effect on indomethacin-induced gastric mucosal damage. The DHEA group, male Sprague-Dawley rats, was administrated with DHEA orally at a dose of 4 mg/day for one week before inducing gastritis with indomethacin (50 mg/kg, p.o.). Histological assay, lipid peroxidation assay, superoxide dismutase (SOD), glutathione peroxidase (GPx) and Catalase activities were determined. Interestingly, it was found that the DHEA pretreatment attenuated the gastric lesion area induced by indomethacin. Rather, the pretreatment with high dose of DHEA led to submucosal edema, leukocyte infiltration in submucosa and mucosal necrosis. The levels of MDA in the DHEA pretreatment were also higher than those in the rats given with vehicle pretreatment. This suggests that the DHEA pretreatment deteriorates severe inflammation in indomethacin-induced gastritis. DHEA supplementation significantly increased SOD activity in the gastric mucosa. However, the catalase and GPx activities were not altered by DHEA. The co-administration of DHEA with an indomethacin might not offer a protective effect against the acute gastritis induced by indomethacin.

Keywords

References

  1. Aragno, M., Parola, S., Brignardello, E., Manti, R., Betteto, S., Tamagno, E., Danni, O. and Boccuzzi, G. (2001). Oxidative stress and eicosanoids in the kidneys of hyperglycemic rats treated with dehydroepiandrosterone. Free Radic. Biol. Med. 31, 935-942 https://doi.org/10.1016/S0891-5849(01)00669-4
  2. Aragno, M., Parola, S., Brignardello, E., Mauro, A., Tamagno, E., Manti, R., Danni, O. and Boccuzzi, G. (2000b). Dehydroepiandrosterone prevents oxidative injury induced by transient ischemia/reperfusion in the brain of diabetic rats. Diabetes 49, 1924-1931 https://doi.org/10.2337/diabetes.49.11.1924
  3. Aragno, M., Parola, S., Tamagno, E., Brignardello, E., Manti, R., Danni, O. and Boccuzzi, G. (2000a). Oxidative derangement in rat synaptosomes induced by hyperglycaemia: restorative effect of dehydroepiandrosterone treatment. Biochem. Pharmacol. 60, 389-395 https://doi.org/10.1016/S0006-2952(00)00327-0
  4. Aragno, M., Tamagno, E., Gatto, V., Brignardello, E., Parola, S., Danni, O. and Boccuzzi, G. (1999). Dehydroepiandrosterone protects tissues of streptozotocin-treated rats against oxida tive stress. Free Radic. Biol. Med. 26, 1467-1474 https://doi.org/10.1016/S0891-5849(99)00012-X
  5. Austin, E. W., Okita, J. R., Okita, R. T., Larson, J. L. and Bull, R. J. (1995). Modification of lipoperoxidative effects of dichloroacetate and trichloroacetate is associated with peroxisome proliferation. Toxicology 97, 59-69 https://doi.org/10.1016/0300-483X(94)02926-L
  6. Bandyopadhyay, D., Biswas, K., Bhattacharyya, M., Reiter, R. J. and Banerjee, R. K. (2002). Involvement of reactive oxygen species in gastric ulceration: protection by melatonin. Indian J. Exp. Biol. 40, 693-705
  7. Beck, P. L., Xavier, R., Lu, N., Nanda, N. N., Dinauer, M., Podolsky, D. K. and Seed, B. (2000). Mechanisms of NSAIDinduced gastrointestinal injury defined using mutant mice. Gastroenterology 119, 699-705 https://doi.org/10.1053/gast.2000.16497
  8. Brignardello, E., Gallo, M., Aragno, M., Manti, R., Tamagno, E., Danni, O. and Boccuzzi, G. (2000). Dehydroepiandrosterone prevents lipid peroxidation and cell growth inhibition induced by high glucose concentration in cultured rat mesangial cells. J. Endocrinol. 166, 401-406 https://doi.org/10.1677/joe.0.1660401
  9. Elizalde, J. I., Mendez, A., Gomez, J., del Rivero, M., Gironella, M., Closa, D., Quintero, E. and Pique, J. M. (2003). Gastric mucosal blood flow changes in Helicobacter pylori infection and NSAID-induced gastric injury. Helicobacter 8, 124-131 https://doi.org/10.1046/j.1523-5378.2003.00133.x
  10. Ernst, P. (1999). Review article: the role of inflammation in the pathogenesis of gastric cancer. Aliment. Pharmacol. Ther. 13 Suppl 1, 13-18 https://doi.org/10.1046/j.1365-2036.1999.00003.x
  11. Green, J. E., Shibata, M. A., Shibata, E., Moon, R. C., Anver, M. R., Kelloff, G. and Lubet, R. (2001). 2-difluoromethylornithine and dehydroepiandrosterone inhibit mammary tumor progression but not mammary or prostate tumor initiation in C3(1)/SV40 T/t-antigen transgenic mice. Cancer Res. 61, 7449-7455
  12. Hayashi, F., Tamura, H., Yamada, J., Kasai, H. and Suga, T. (1994). Characteristics of the hepatocarcinogenesis caused by dehydroepiandrosterone, a peroxisome proliferator, in male F-344 rats. Carcinogenesis 15, 2215-2219 https://doi.org/10.1093/carcin/15.10.2215
  13. Khalil, A., Fortin, J. P., LeHoux, J. G. and Fulop, T. (2000). Age-related decrease of dehydroepiandrosterone concentrations in low density lipoproteins and its role in the susceptibility of low density lipoproteins to lipid peroxidation. J. Lipid Res. 41, 1552-1561
  14. Khalil, A., Lehoux, J. G., Wagner, R. J., Lesur, O., Cruz, S., Dupont, E., Jay-Gerin, J. P., Wallach, J. and Fulop, T. (1998). Dehydroepiandrosterone protects low density lipoproteins against peroxidation by free radicals produced by gamma-radiolysis of ethanol-water mixtures. Atherosclerosis 136, 99-107 https://doi.org/10.1016/S0021-9150(97)00194-9
  15. Kroboth, P. D., Salek, F. S., Pittenger, A. L., Fabian, T. J. and Frye, R. F. (1999). DHEA and DHEA-S: a review. J. Clin. Pharmacol. 39, 327-348 https://doi.org/10.1177/00912709922007903
  16. Kuebler, J. F., Jarrar, D., Wang, P., Bland, K. I. and Chaudry, I. H. (2001). Dehydroepiandrosterone restores hepatocellular function and prevents liver damage in estrogen-deficient females following trauma and hemorrhage. J. Surg. Res. 97, 196-201 https://doi.org/10.1006/jsre.2001.6155
  17. La Vecchia, C. and Franceschi, S. (2000a). Nutrition and gastric cancer. Can J. Gastroenterol. 14 Suppl D, 51D-54D https://doi.org/10.1155/2000/869862
  18. La Vecchia, C. and Franceschi, S. (2000b). Nutrition and gastric cancer with a focus on Europe. Eur. J. Cancer Prev. 9, 291-295 https://doi.org/10.1097/00008469-200010000-00001
  19. Mastrocola, R., Aragno, M., Betteto, S., Brignardello, E., Catalano, M. G., Danni, O. and Boccuzzi, G. (2003). Pro-oxidant effect of dehydroepiandrosterone in rats is mediated by PPAR activation. Life Sci. 73, 289-299 https://doi.org/10.1016/S0024-3205(03)00287-X
  20. Morgan, E. T. (2001). Regulation of cytochrome p450 by inflammatory mediators: why and how? Drug Metab. Dispos. 29, 207-212
  21. Nieschlag, E., Loriaux, D. L., Ruder, H. J., Zucker, I. R., Kirschner, M. A. and Lipsett, M. B. (1973). The secretion of dehydroepiandrosterone and dehydroepiandrosterone sulphate in man. J. Endocrinol. 57, 123-134 https://doi.org/10.1677/joe.0.0570123
  22. Oberley, L. W. and Spitz, D. R. (1984). Assay of superoxide dismutase activity in tumor tissue. Methods Enzymol. 105, 457-464 https://doi.org/10.1016/S0076-6879(84)05064-3
  23. Prough, R. A., Webb, S. J., Wu, H. Q., Lapenson, D. P. and Waxman, D. J. (1994). Induction of microsomal and peroxisomal enzymes by dehydroepiandrosterone and its reduced metabolite in rats. Cancer Res. 54, 2878-2886
  24. Shilkaitis, A., Green, A., Punj, V., Steele, V., Lubet, R. and Christov, K. (2005). Dehydroepiandrosterone inhibits the progression phase of mammary carcinogenesis by inducing cellular senescence via a p16-dependent but p53-independent mechanism. Breast Cancer Res. 7, R1132-1140 https://doi.org/10.1186/bcr1350
  25. Sinet, P. M., Michelson, A. M., Bazin, A., Lejeune, J. and Jerome, H. (1975). Increase in glutathione peroxidase activity in erythrocytes from trisomy 21 subjects. Biochem. Biophys Res Commun 67, 910-915 https://doi.org/10.1016/0006-291X(75)90763-9
  26. Swierczynski, J., Bannasch, P. and Mayer, D. (1996a). Increase of lipid peroxidation in rat liver microsomes by dehydroepiandrosterone feeding. Biochim. Biophys. Acta. 1315, 193-198 https://doi.org/10.1016/0925-4439(95)00125-5
  27. Swierczynski, J., Kochan, Z. and Mayer, D. (1997). Dietary alpha-tocopherol prevents dehydroepiandrosterone-induced lipid peroxidation in rat liver microsomes and mitochondria. Toxicol. Lett. 91, 129-136 https://doi.org/10.1016/S0378-4274(97)03882-4
  28. Swierczynski, J. and Mayer, D. (1996b). Dehydroepiandrosterone-induced lipid peroxidation in rat liver mitochondria. J. Steroid Biochem. Mol. Biol. 58, 599-603 https://doi.org/10.1016/0960-0760(96)00081-7
  29. Wallace, J. L. (1997). Nonsteroidal anti-inflammatory drugs and gastroenteropathy: the second hundred years. Gastroenterology 112, 1000-1016 https://doi.org/10.1053/gast.1997.v112.pm9041264
  30. Williams, M. R., Ling, S., Dawood, T., Hashimura, K., Dai, A., Li, H., Liu, J. P., Funder, J. W., Sudhir, K. and Komesaroff, P. A. (2002). Dehydroepiandrosterone inhibits human vascular smooth muscle cell proliferation independent of ARs and ERs. J. Clin. Endocrinol. Metab. 87, 176-181 https://doi.org/10.1210/jc.87.1.176
  31. Wu, G. H. and Qin, X. Y. (2004). Nutrition support in patients with gastric cancer. Zhonghua. Yi. Xue. Za. Zhi. 84, 179-181

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