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Urate Synthesis and Oxidative Stress in Phenytoin Hepatotoxicity: The Role of Antioxidant Vitamins |
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Itemobong S. Ekaidem,
Itoro F. Usoh,
Monday I. Akpanabiatu,
Friday E. Uboh and Henry D. Akpan |
Abstract:
Phenytoin is known to induce microsomal enzymes including
xanthine oxidase which catalyzes uric acid synthesis with superoxides as byproducts,
thus contributing to the oxidative stress of phenytoin hepatotoxicity. To investigate
the role of antioxidant vitamins in ameliorating phenytoin induced hepatic changes
through possible actions on xanthine oxidase activities as measured by urate
concentration. Growing albino rats of Wistar strain were randomly divided into
8 groups of 7 rats each. Group 2, 3, 4, 5, 6, 7 and 8 were treated with phenytoin
alone, phenytoin + folic acid, phenytoin + vitamin E, phenytoin + vitamin E
+ vitamin C, phenytoin + vitamin C, phenytoin + folic acid + vitamin E and phenytoin
+ vitamin E + vitamin C + folic acid respectively while animals in group 1 were
given normal saline to serve as control. Serum concentrations of uric acid,
albumin, total protein and the activities of aspartate and alanine aminotransferases
(AST and ALT) and catalase were measured spectrophotometrically using appropriate
commercial reagent kits. Result showed that administration of phenytoin alone
caused significant (p<0.05) increase in serum levels of globulin, uric acid,
AST and ALT activities while the levels of albumin and catalase were reduced
significantly (p<0.05). Supplementation of phenytoin treatment with vitamins
resulted in various degrees of protection. However, the elevated level of uric
acid in serum was not significantly (p<0.05) affected by any of the vitamins
used and there was no significant correlation between the activities of aminotransferases
and uric acid concentration in the vitamin treated animals as was observed between
aminotransferasdes and catalase. The findings in this study suggest that antioxidant
vitamins were able to ameliorate phenytoin hepatotoxic effects by improving
oxidant radicals removal in the animals but would not inhibit futher generation
of the superoxides by xanthine oxidase activity and that xanthine oxdase may
contribute significantly to the oxidative stress of phenytoin therapy.
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How to cite this article:
Itemobong S. Ekaidem, Itoro F. Usoh, Monday I. Akpanabiatu, Friday E. Uboh and Henry D. Akpan, 2014. Urate Synthesis and Oxidative Stress in Phenytoin Hepatotoxicity: The Role of Antioxidant Vitamins. Pakistan Journal of Biological Sciences, 17: 1179-1184.
DOI: 10.3923/pjbs.2014.1179.1184
URL: https://scialert.net/abstract/?doi=pjbs.2014.1179.1184
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