Nobiletin Protects from Renal Ischemia-Reperfusion Injury in Rats by Suppressing Inflammatory Cytokines and Regulating iNOS-eNOS Expressions.

Ischemia-reperfusion injury is an organ failure caused by hypoxia and reperfusion, which is closely associated with oxidative stress and inflammation. In this study, we investigated whether nobiletin had protective effects on inflammatory parameters, oxidative damage, iNOS-eNOS expressions, and histopathological structure of renal tissue in rats with renal ischemia-reperfusion injury. For this purpose, 24 rats were divided into 4 groups: group 1 (Control), group 2 (Ischemia-Reperfusion-IR), group 3 (Nobiletin-10 mg/kg p.o.), group 4 (Nobiletin + IR). The study was continued for 7 days. At the end of the study, urea (p < 0.05), creatine (p < 0.05), MDA (p < 0.001), TNF-alpha (p < 0.001), IL-1 beta (p < 0.05), and IL-6 (p < 0.001) levels increased in the IR group; however, a significant decrease occurred in group 4 (Nobiletin + IR) and it reached the control group levels. In the IR group, GSH (p < 0.01) levels, and GSH.Px (p < 0.01) and CAT (p < 0.05) activities decreased whereas they increased significantly in group 4 (Nobiletin + IR) and reached the same levels as the control group. In histopathological analyses, destruction and increased iNOS-eNOS expressions in the IR group showed a significant decrease in group 4 (Nobiletin + IR). As a result, the application of nobiletin has shown that it has protective effects by reducing kidney damage caused by IR injury.