Renoprotective Potential of Nateglinide in an Acute Kidney Injury Model.

Abstract

Nateglinide (Nat) is an oral antidiabetic agent of the meglitinide class that has been reported to exert protective effects beyond glycemic control, particularly against oxidative stress and inflammation. Since oxidative stress and inflammation play a key role in the pathogenesis of acute kidney injury (AKI), especially following ischemia/reperfusion (I/R), this study aimed to evaluate the potential renoprotective effects of Nat in a rat model of I/R-induced AKI. Forty male Sprague Dawley rats were randomly divided into four groups (= 10): Control, I/R, I/R + Nat (50 mg/kg), and I/R + Nat (100 mg/kg). Bilateral renal ischemia was induced by clamping renal arteries for 45 min, followed by 24 h of reperfusion. Nat was administered orally 1 h before ischemia. Renal levels of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and thiobarbituric acid reactive substances (TBARSs) were assessed. Serum blood urea nitrogen (BUN), creatinine, tumor necrosis factor-&#x3b1; (TNF-&#x3b1;), and interleukin-1&#x3b2; (IL-1&#x3b2;) were also measured, and histopathological analyses were performed. Nat significantly increased renal antioxidant parameters and reduced TBARS levels. Moreover, Nat markedly decreased serum BUN, creatinine, TNF-&#x3b1;, and IL-1&#x3b2; levels compared with the I/R group (< 0.05). Histopathology confirmed attenuated renal damage in Nat-treated groups (< 0.0001). These results indicate that Nat confers significant renoprotection against renal I/R injury via suppression of oxidative stress and inflammation.