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.
ABSTRACT
The hypolipidemic, antioxidative and hepatoprotective activities of 200 and 300mg/kg body weight ethanolic extract of dried flower of Hibiscus sabdariffa L. (HSE) were assessed in rats treated with 0.25ml/kg body weight (intraperitoneally) of carbon tetrachloride (CCl4). Hepatic malondialdehyde (MDA), serum lipid profile, serum vitamins A, C and β- carotene, alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) activities were measured. The oral administration of the extracts showed a significant (P<0.05) dose-dependent decrease in the CCl4- induced MDA formation in liver. Also HSE pretreatment, showed a significant increase in HDL-C concentration and decrease in the levels of total cholesterol, LDL-C and TG as compared to control. The levels of vitamins A, C, and β- carotene were shown to be significantly (P<0.05) decreased and increased respectively in CCl4 and HSE treated groups when compared with the control. The increase in the levels of these vitamins might not be unconnected with the antioxidant properties possessed by the extract. The extract also displayed a strong hepatoprotective effect as it significantly reduced CCl4- induced hepatotoxicity in rats, as judged from the serum activities of ALT, AST, and ALP. These results suggest that the ethanolic extract of dried flower of Hibiscus sabdariffa L. possesses antioxidant, hepatoprotective and hypolipidemic effects on CCl4-induced oxidative stress in rats.