Hesperidin provides dose-dependent renal protection from cisplatin-induced injury, mediated by its regulation of Beclin-1 and LC3-II.

Cisplatin (cis-diamminedichloroplatinum (II), Cis) is identified as an anti-cancer agent applied in treating malignant diseases. Evidence indicates that the pathological mechanisms of the nephrotoxicity induced by Cis have been uncertain, and no effective medicine has been found for Cis nephrotoxicity. Hesperidin has been reported to have several beneficial effects such as antioxidant property. The present research explored how hesperidin affects Cis nephrotoxicity by regulating autophagy and antioxidant effect. The study involved 30 male Wistar rats (200-220 g) randomized to five groups (n = 6): Sham group received no treatment. Cis group was treated with a single dose of cisplatin (7.5 mg/kg) intraperitoneally on Day 4. The remaining groups received, by gavage, daily doses of hesperidin (50, 100, or 200 mg/kg) for seven days plus a single dose of intraperitoneal cisplatin (7.5 mg/kg) on Day 4. On Day 8, xylazine + ketamine was used to anesthetize the rats to obtain tissue and blood samples. Findings indicated that Cis elevated malondialdehyde, BUN and Cr levels, while simultaneously reducing total antioxidant capacity (TAC) and inhibiting microtubule-associated protein light chain 3 (LC3-II) and Beclin-1. Notably, hesperidin (100, 200 mg/kg) could increase mRNA LC3-II and Beclin-1 expression. Moreover, animals receiving hesperidin (100, 200 mg/kg) experienced increased TAC and decreased MDA levels. Hesperidin generally protects kidney tissue in Cis nephrotoxicity through regulating autophagy. Hesperidin demonstrated optimal efficacy at a dose of 200 mg/kg.