Hibiscetin Mitigates Cisplatin-evoked Renal Toxicity through the Modulation of Activated Caspase-3/COX-2/iNOS/p53

Background: Renal toxicity is a significant concern in various clinical settings, yet its examination with a focus on particular parameters remains limited. A variety of factors including medications, chemicals, environmental toxins, and medical conditions can contribute to renal toxicity. Cisplatin (CP) is a widely used chemotherapeutic agent for the treatment of various cancers. However, one of its significant side effects is nephrotoxicity, which can lead to acute kidney injury. The purpose of this research was to investigate the potential protective effects of hibiscetin against CP-induced nephrotoxicity in rats. Methods: The study employed a simple randomization method, involving four groups of six rats each. The groups were desig-nated as follows: the normal control group, the CP injected group, the CP + hibiscetin group (10 mg/kg), and the hibiscetin-treated group (10 mg/kg) for 25 days. Various biochemical parameters were measured, including kidney function markers [blood urea nitrogen (BUN), serum albumin, creatinine, creatinine clearance], tubular damage biomarkers [N-Acetyl-b-D-glucosaminidase (NAG)], antioxidant levels [superoxide dismutase (SOD), glutathione transferase (GST), catalase (CAT), and malondialdehyde (MDA)], anti-inflammatory markers [interleukins-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukins-33 (IL-33), interleukins-6 (IL-6), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2)], and apoptotic markers (Caspase-3 and p53). The assessment was performed using serum and urine samples. Antioxidants, inflammatory markers, and apoptotic markers were measured using kidney tissue homogenate. Results: The findings of the study show that the administration of hibiscetin significantly reduced the biochemical, enzymatic, and inflammatory alterations induced by CP in rats. This protective effect was evident in the modulation of various biomarkers, including IL-1β, IL-6, IL-33, TNF-α, iNOS, COX-2, p53, and Caspase-3 (Casp-3). Notably, hibiscetin exhibited statistically significant effects in counteracting CP-induced nephrotoxicity (p < 0.05). Conclusions: The current study suggests that hibiscetin may be effective in nephroprotection in rats induced with CP.