The Effect of Thymoquinone on the Activities of Drug Metabolizing Enzymes Following Gentamicin - Induced Nephrotoxicity in Rats.

Alharthi, Abdulla Ayead; Elsheikh, Hatim Ali

Objectives: The present study investigated the effects of thymoquinone on the renal activities of drug-metabolizing enzyme following gentamicin-induced nephrotoxicity in Wistar breed rats. Intraperitoneal administration of thymoquinone alone in rats at the dose rate of 10 mg/kg daily for ten consecutive days did not produce toxic effects in the kidney or change its drug metabolizing capacity. Results: However, nephrotoxicity was produced in Rats injected intraperitoneally with gentamicin daily at the dose rate of 80 mg/kg body weight for ten consecutive days, where there was significant increase in the concentrations of serum creatinine and blood urea compared to control rats (P < 0.0005) and those treated with thymoquinone alone (P < 0.0005), or those given thymoquinone and gentamicin concomitantly (10 mg/kg and 80 mg/kg intraperitoneally daily for ten consecutive days, respectively) (P < 0.0005). In addition, injection of gentamicin illustrated a tendency to decrease, although not statistically significant, in the kidney concentration of reduced glutathione. Furthermore, gentamicin administration resulted in a significant decrease in the renal concentration of cytochrome P-450 (P < 0.05), while it could not produce significant changes in the renal activities of phase II drug metabolizing enzymes namely, UDP- glucuronyltransferase and glutathione-S-transferase compared to values obtained for control rats and those treated with thymoquinone alone or coadministered with gentamicin. These findings confirm the nephrotoxic effects of gentamicin and its ability to decrease the renal activities of phase I drug metabolizing enzymes as shown by the significant reduction in the concentration of cytochrome P-450 in the kidneys of treated rats. Conclusion: It can be concluded that thymoquinone coadministration with gentamicin can induce protective effects against gentamicin nephrotoxicity accompanied with restoration of the concentration of cytochrome P-450 to normal levels in the kidneys of treated rats.

PHYTOCHEMICALS; DRUG metabolism; GENTAMICIN; NEPHROTOXICOLOGY; DRUG efficacy; DRUG administration; LABORATORY rats

Egyptian Journal of Hospital Medicine, 2010, Vol 41, p532

1687-2002

Academic Journal