Phenytoin Induced Changes in Glucose and Lipid Metabolism is Related to Increased Urate Synthesis
Journal Title: Journal of Advances in Medicine and Medical Research - Year 2016, Vol 16, Issue 7
Abstract
Aim: The study was to investigate the relationship of phenytoin-associated hyperuricaemia with the hyperglycaemia and dyslipidaemia caused by phenytoin administration. Methods: Forty-two albino Wistar rats were randomly divided into six (6) groups of 7 rats each. Group 1 animals served as the control (receiving normal saline 0.50 ml). Groups 2,3,4,5 and 6 received phenytoin, phenytoin + vitamin C, phenytoin + vitamin E, phenytoin +vitamin E +vitamin C and phenytoin + allopurinol respectively. The drugs were administered once daily for four weeks by oral intubation as follows: Phenytoin: 5 mg/kg body weight of rat, vitamin C: 1.4 mg/kg body weight of rat, Vitamin E: 10 IU/kg body weight of rat and allopurinol 5mg/kg body weight of rats. Appropriate immunoassay or spectrophotometric methods were used for analysis of fasting plasma glucose, insulin, cholesterol, triglyceride and catalase activities. Results: Showed a significant elevation of serum uric acid following phenytoin administration (p= 0.000) that were not reversed by co-administration of antioxidant vitamins but were reduced by allopurinol administration. Serum catalase activities which were significantly depressed by phenytoin treatment were reversed by antioxidant Vitamins C, E or allopurinol. The concentration of fasting plasma glucose, insulin resistance index, total cholesterol and triglyceride were significantly increase [(59.5%: p=0.001), (87.9%: p=0.005), (35.7%: p=0.000), (34.5% p=0.027)] respectively by phenytoin administration compared to control. However, the values of these parameters were not significantly lowered by antioxidant Vitamins, but significant reduction (p=0.017) to values similar to those of normal control group were observed in the group receiving both phenytoin and allopurinol. Fasting plasma insulin levels were not significantly (16.8%: p=0.137) affected by these drug treatments. Pearson bivariate correlation analysis of data of the experimental groups and control showed significant positive correlation between uric acid and fasting plasma glucose (r=0.598, P=0.000), fasting plasma insulin (r=0.394, P=0.010), insulin resistance index (HOMAIR: r=0.551, P=0.000), total cholesterol (r=0.677, P=0.000) and triglyceride (r=0.490, P.0.001). Conclusion: We conclude that the metabolic toxicities of phenytoin associated with impaired glucose metabolism, insulin resistance and dyslipidaemia, are related to phenytoin induced hyperuricaemia.
Authors and Affiliations
Itemobong S. Ekaidem, Itoro F. Usoh, Friday E. Uboh
Keywords
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- EP ID EP341266
- DOI 10.9734/BJMMR/2016/24851
- Views 95
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