Seyhan GÜMÜŞLÜ, Suna ÖMEROĞLU, Seda DEVAY DUYGULU, Mustafa KAVUTÇU, Nilüfer BAYRAKTAR, Mine TAŞLIPINAR YAVUZ, Orhan CANBOLAT

The effects of stobadine on purine metabolism in rats treated with carbon tetrachloride

The aim of the present study was to investigate the relationship between liver damage induced by carbon tetrachloride (CCl4) and adenosine deaminase (ADA), 5'-nucleotidase (5'NT), xanthine oxidase (XO) enzyme activities, and malondialdehyde (MDA) levels. The effect of stobadine on purine metabolism was also evaluated. Materials and methods: This study measured the effect of CCl4 on ADA, 5'NT, XO enzyme activities, and MDA levels, and measured the histopathologic changes in liver cells. Results: Our research found that ADA, XO activities, and MDA levels increased in the CCl4 group when compared with the control group. This was also supported by the histopathological changes in the CCl4 and CCl4+stobadine group found when compared with the control group. Stobadine could not protect cells against CCl4 damage. Conclusion: The present study helps explain the biochemical mechanisms of liver injury formed by CCl4 and shows the relationship between the purine degradation pathway and CCl4induced cellular toxic effect. Cellular damage is dependent upon the biochemical response to increased purine degradation pathway enzyme activities, which also may be responsible for decreasing liver cellular adenosine levels and S-adenosyl-methionine and increasing superoxide anion and hydrogen peroxide levels. It is suggested that the inhibition of key enzymes of the purine degradation pathway (particularly ADA and XO) may prevent liver damage.

Anahtar Kelimeler:

Key words: CCl4, adenosine deaminase, 5'-nucleotidase, xanthine oxidase, malondialdehyde, S-adenosyl-methionine

The effects of stobadine on purine metabolism in rats treated with carbon tetrachloride

Keywords:

Key words: CCl4, adenosine deaminase, 5'-nucleotidase, xanthine oxidase, malondialdehyde, S-adenosyl-methionine,

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1. Parola M, Leonarduzzi G, Biasi F, Albano E, Biocca ME, Poli P et al. Vitamin E dietary supplementation protects against carbon tetrachloride-induced chronic liver damage and cirrhosis. Hepatology 1992; 16: 1014-21.
2. Hernandez-Munoz R, Diaz-Munoz M, Lopez V, LopezBarrera F, Yanez L, Virdio S et al. Balance between oxidative damage and proliferative potential in an experimental rat model of CCl4 -induced cirrhosis. Protective role of adenosine administration. Hepatology 1997; 26: 1100-10.
3. Poli G, Cottalasso D, Pronzato MA, Chiarpotto E, Marinari UM. Lipid peroxidation and covalent binding in early functional impairment of liver Golgi apparatus by carbon tetrachloride. Cell Biochem Func 1990; 8: 1-10.
4. Recknagel R, Glende EA, Dolak JA, Waller RL. Mechanisms of carbon tetrachloride toxicity. Pharma Th er 1989; 43: 139-54.
5. Slater TF. Free radicals as reactive intermediates in injury. In: Snyder IR, Parke DV, Kocsis JJ, Jollow DJ, Gibson GG, Witmer CM, editors. Biological reactive intermediates II: chemical mechanisms and biological eff ects. New York: Plenum Press; 1982. p.575-89.
6. Arii S, Monden K, Hai S, Sasaoki T, Adachi Y, Funaki N et al. Depressed function of Kupff er cells in rats with CCl4 -induced liver cirrhosis. Res Exp Med 1990; 190: 173-82.
7. Canbolat O, Durak I, Cetin R, Kavutcu M, Demirci S, Oztürk S. Activities of adenosine deaminase, 5’-nucleotidase, guanase, and cytidine deaminase enzymes in cancerous and noncancerous human breast tissues. Breast Cancer Res Treat 1996; 37: 189-93.
8. Durak I, Işik AC, Canbolat O, Akyol O, Kavutçu M. Adenosine deaminase, 5’-nucleotidase, xanthine oxidase, superoxide dismutase, and catalase activities in cancerous and noncancerous human laryngeal tissues. Free Radic Biol Med 1993; 15: 681-4.
9. Murray JL, Mehta K, Lopez-Berestein G. Induction of adenosine deaminase and 5’-nucleotidase activity in cultured human blood monocytes and monocytic leukemia (THP-1) cells by diff erentiating agents. J Leukoc Biol 1988; 44: 205-11.
10. Iizuka H, Koizumi H, Kamigaki K, Aoyagi T, Miura Y. Two forms of adenosine deaminase in pig epidermis. J Dermatol 1981; 8: 91-5.
11. Donofrio J, Coleman MS, Hutton JJ, Daoud A, Lampkin B, Dyminski J. Overproduction of adenosine deoxynucleosides and deoxynucleotides in adenosine deaminasedefi ciency with severe combined immunodefi ciency disease. J Clin Invest 1978; 62: 884-7.
12. Chang PK, Gordon RK, Tai J, Zeng GC, Doctor BP, Pardhasaradhi K et al. S-adenosylmethionine and methylation. FASEB J 1996; 10: 471-80.
13. Caro AA, Cederbaum AI. Antioxidant properties of S-adenosyl-L-methionine in Fe2+-initiated oxidations. Free Radic Biol Med 2004; 36: 1303-16.
14. Lu SC, Huang ZZ, Yang H, Mato JM, Avila MA, Tsukamoto H. Changes in methionine adenosyltransferase and S-adenosylmethionine homeostasis in alcoholic rat liver. Am J Physiol Gastrointest Liver Physiol 2000; 279: 178-85.
15. Meisel AD, Natarjan C, Sterba G, Diamond HS. Cyclic nucleotide levels and mechanism of inhibition of leukocyte function by adenosine deaminase inhibition. Adv Exp Med Biol 1979; 122: 251-7.
16. Hasan NM, Cundall RB, Adams GE. Eff ects of hypoxia and reoxygenation on the conversion of xanthine dehydrogenase to oxidase in Chinese hamster V79 cells. Free Radic Biol Med 1991; 11: 170-85.
17. Brass CA, Narciso J, Gollan JL. Enhanced activity of the free radical producing enzyme xanthine oxidase in hypoxic rat liver. Regulation and pathophysiologic signifi cance. J Clin Invest 1991; 87: 424-31.
18. Sakuma S, Miyoshi E, Sadatoku N, Fujita J, Negoro M, Arakawa Y et al. Monochloramine produces reactive oxygen species in liver by converting xanthine dehydrogenase into xanthine oxidase. Toxicol Appl Pharmacol 2009; 239: 268-72.
19. Stolc S, Bauer V, Benes L, Tichy M. Medicine with antiarrhythmic and antihypoxic activity and its method of preparation. Patents: CS 229 067, SWED. 8204693-9, BELG. 894148, SWISS 651 754, BRD. P-3231088, SPAIN 553 017, JAP. 151 4040. 1983.
20. Stasko A, Ondrias K, Misik V, Szöchova H, Gergel D. Stobadine: a novel scavenger of free radicals. Chem 1990; 4: 493-500.
21. Steenken S, Sundwuist AR, Jovanovic SV, Crockett R, Sies H. Antioxidant activity of the pyridoindole stobadine: pulse radiolytic characterization of one electron oxidized stobadine and quenching of singlet molecular oxygen. Chem Res Toxicol 1992; 5: 355-60.
22. Necas J, Bartosikova L, Benes L, Janostikova E, Bartosik T, Klusakova J et al. Infl uence of antioxidant eff ect of stobadine derivative in condition of kidney ischemia-reperfusion in a pre-clinical experiment (eff ect in prophylaxis). Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2005; 149: 385- 8.
23. Ulusu NN, Sahilli M, Avci A, Canbolat O, Ozansoy G, Ari N et al. Pentose phosphate pathway, glutathione-dependent enzymes and antioxidant defense during oxidative stress in diabetic rodent brain and peripheral organs: eff ects of stobadine and vitamin E. Neurochem Res 2003; 28: 815-23.
24. Rozga J. Animal models of liver regeneration. In: Souba WW, Souba DG, editors. Surgical research. Wilmore (CA): Academic Press; 2001. p.703-7.
25. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193: 265-75.
26. Donald WM. Enzymes. In: Tietz NW, editor. Textbook of clinical chemistry. Philadelphia (PA): W.B. Saunders Company; 1986. p.718-20.
27. Guisti G. Enzyme activities. In: Bergmeyer UH, editor. Methods of enzymatic analysis. Weinheim: Verlag Chemie; 1974. p.1092-8.
28. Hashimoto S. A new spectrophotometric assay method of xanthine oxidase in crude tissue homogenate. Anal Biochem 1974; 62: 426-35.
29. Van Ye TM, Roza AM, Pieper GM, Henderson J Jr, Johnson JP, Adams MB. Inhibition of intestinal lipid peroxidation does not minimize morphological damage. J Surg Res 1993; 55: 553-8.
30. Simile MM, Banni S, Angioni E, Carta G, De Miglio MR, Muroni MR et al. 5’-Methylthioadenosine administration prevents lipid peroxidation and fi brogenesis induced in rat liver by carbon-tetrachloride intoxication. J Hepatol 2001; 34: 386-94.
31. Lu SC, Mato JM. Role of methionine adenosyltransferase and S-adenosylmethionine in alcohol-associated liver cancer. Alcohol 2005; 35: 227-34.