Investigation of the protective effects of Nateglinide in rats with acute kidney injury

Aim: Nateglinide (Nat), an oral antidiabetic agent of the meglitinide class, has shown potential protective effects beyond glycemic control, particularly against oxidative stress and inflammation. Oxidative stress imbalance and elevated inflammation contribute to the pathogenesis of acute kidney injury (AKI). AKI induced by ischemia/reperfusion (I/R) is characterized by abrupt kidney dysfunction due to cellular damage and inflammatory responses. This thesis aimed to evaluate the protective effects and mechanisms of Nat in an experimental I/R-induced AKI model in rats. Materials and Methods: Forty male Sprague-Dawley rats were divided into four groups (n=10 each): Control, I/R, I/R+Nat (50 mg/kg), and I/R+Nat (100 mg/kg). Bilateral renal arteries were clamped for 45 minutes to induce ischemia, followed by 24 hours of reperfusion. Nat was administered orally 1 hour before ischemia. Kidney tissue levels of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and malondialdehyde (MDA) were measured, along with histopathological assessments. Serum levels of BUN, creatinine, TNF-α, and IL-1β were measured by ELISA. Results: Nat treatment significantly increased renal SOD, CAT, and GSH levels, while reducing MDA, TNF-α, IL-1β, BUN, and creatinine levels. Histopathological analysis showed reduced tissue injury in Nat-treated groups. Conclusion: Nat exhibits significant protective effects against renal I/R injury by reducing oxidative stress and inflammation. Keywords: Kidney, Nateglinide, Ischemia/reperfusion, Inflammation, Oxidative damage