Colistin-induced renal injury: Amelioration by thymoquinone in rats

Objectives: Colistin, a re-emerged antibiotic, is used as a last resort for the treatment of multidrug-resistant Gram-negative bacteria. Nephrotoxicity is a major concern encountered with its clinical use. In this study, we investigated the ameliorative effect of thymoquinone (TQ) on colistin-induced renal injury in rats. Materials and Methods: Rats were divided into five groups, with six rats in each group, and colistin (450,000 IU/kg/day) was administered intramuscularly for 7 days, except in the control groups. Two groups of rats administered colistin were pre-treated with TQ at 10 mg/kg/day and 20 mg/kg/day orally. Blood and urine samples were collected on days 0 and 8 for biochemical analysis. Oxidative stress, antioxidant assays, and histopathological assessments were performed on kidney samples. Results: Colistin administration in rats resulted in a significant increase in blood urea, serum creatinine, and urine creatinine on day 8 compared to baseline values and the normal control group. TQ at 10 mg/kg attenuated colistin-induced elevations in blood urea and urine creatinine, while serum creatinine remained elevated. TQ at 20 mg/kg attenuated colistin-induced elevation of blood urea and serum creatinine, while urine creatinine remained elevated. TQ treatment demonstrated a mitigating effect on colistin-induced oxidative changes, with levels of malondialdehyde and antioxidant enzymes catalase and superoxide dismutase comparable to the normal control group. In addition, TQ prevented the reduction in glutathione and total protein levels observed in colistin-administered rats. Histopathological examination revealed significant glomerular and tubular changes in colistin-administered rats, whereas these changes were minimal in rats treated with TQ. Conclusion: From this study, we concluded that TQ has the potential to ameliorate colistin-induced nephrotoxicity.