Protective Effects of Ethyl Pyruvate and Rutin Hydrate Against Colistin-Induced Nephrotoxicity in Rats

Background: Colistin is increasingly being used as a last-line treatment option for multidrug-resistant Gram-negative infections; however, its clinical use remains limited due to its nephrotoxic side effects. This study investigated the potential nephroprotective effects of ethyl pyruvate (EP) and rutin hydrate (RH), alone and in combination, against colistin-induced renal damage. Methods: Forty-nine adult male Wistar albino rats were allocated into seven groups, and all agents were administered intraperitoneally once daily for seven days. On the eighth day, one kidney of each animal was perfused using a Langendorff system to measure perfusion pressure, while samples from the contralateral kidney and blood were used for biochemical, molecular, and histopathological analyses. Results: In the colistin group, urea, creatinine, total oxidant status, and perfusion pressure were significantly higher than in the control, EP, and RH groups (p < 0.05). Oxidative stress index, tissue MDA, KIM-1, caspase-3, and PUMA levels were also markedly increased. All of these parameters decreased in the treatment groups, with the lowest values for most parameters in the group receiving both EP and RH, which also showed the best-preserved renal architecture. Conclusions: These findings suggest that EP and RH may be promising adjuvant agents against colistin-induced nephrotoxicity. Combined EP and RH co-treatment showed numerically greater protection across most assessed parameters, although an overall advantage over single-agent co-treatment was not statistically established.