Materials and Methods: In general, 30 male Wistar rats were randomized and placed into sham, IR, hesperetin, dimethyl sulfoxide (DMSO), and IR+hesperetin groups. The rats in the hesperetin and IR+hesperetin groups received a 50 mg/kg dose of hesperetin dissolved in DMSO intraperitoneally. In the IR+hesperetin group, hesperetin was injected exactly prior to reperfusion. To induce skeletal muscle ischemia, the femoral artery was clamped for two hours. Following a 24-hour period of reperfusion, the samples of blood were collected for renal function tests and oxidative stress measurements. Next, the rats were euthanized, and histological analyses were conducted on their removed kidneys.

Results: Based on the results, urea and creatinine serum levels were significantly higher in the IR group (P < 0.05) whereas they significantly reduced following treatment with hesperetin (P < 0.05). The concentration of malondialdehyde (P < 0.05) increased for the IR group while those of superoxide dismutase (P < 0.05) and glutathione peroxidase (P < 0.05) activities were lower than the other groups. The analysis of renal tissues in the IR group showed glomerular necrosis, degeneration, and necrosis of the tubular epithelium, protein casts, interstitial edema, and inflammation. Finally, the degree of renal injury was significantly ameliorated (P < 0.05) in rats treated with hesperetin.

Conclusions: Overall, the results indicated that in rats, hesperetin could reduce renal injury that has been induced through skeletal muscle IR.