Aloesin mitigates cisplatin-induced nephrotoxicity by suppressing NF-κB-mediated oxidative stress and modulating Bax/Bcl-2/caspase pathways.

Cisplatin (CP) is a highly effective, heavy-metal chemotherapeutic agent widely utilized in the treatment of various solid tumors. But its use in therapeutic settings is fundamentally constrained by dosage toxicities, most notably severe nephrotoxicity. Aloesin, a bioactive C-glycosylated chromone naturally derived from Aloe vera, possesses strong antioxidant and anti-inflammatory properties. This investigation clarifies the precise molecular mechanisms by which aloesin attenuates CP-induced renal injury in a rodent model. A total of 36 male Wistar rats were randomly assigned to six experimental groups: (I) Normal control (vehicle only), (II) CP (5 mg/kg, i.p.), (III) CP + Aloesin (20 mg/kg, p.o.), (IV) CP + Aloesin (40 mg/kg, p.o.), (V-VI) Aloesin alone (20 and 40 mg/kg, p.o.). The study followed a preventive design; aloesin was administered orally throughout the 25-day experimental period, concurrent with CP. Nephrotoxicity was induced in the respective groups via four intraperitoneal injections of CP (5 mg/kg) administered at 5-day intervals (days 1, 6, 11, and 16). At the conclusion of the 25-day timeline, physiological parameters, serum creatinine (Scr), blood urea nitrogen (BUN), and lipid profiles were evaluated. Additionally, inflammatory modulators (TNF-α, IL-1β, IL-6, NF-κB), tissue apoptotic indicators (Caspase-3, Caspase-9, Bax, Bcl-2), and oxidative stress markers (MDA, SOD, GSH, CAT) were quantified from renal tissue homogenates alongside semi-quantitative histopathological evaluation. CP administration induced profound renal impairment, characterized by elevated Scr and BUN, extensive lipid peroxidation, and the depletion of endogenous antioxidants. Concurrent treatment with aloesin significantly preserved renal function, reduced MDA levels, and restored SOD, CAT, and reduced GSH activities. Furthermore, aloesin significantly reduced renal tissue levels of NF-κB, TNF-α, IL-1β, IL-6, Bax, Caspase-3, and Caspase-9, while improving Bcl-2 levels and decreasing the Bax/Bcl-2 ratio, suggesting attenuation of inflammatory and apoptotic pathways. Histopathological evaluation confirmed that aloesin effectively preserved renal tubular morphology without causing any independent physiological or systemic toxicity. These findings demonstrate that aloesin exerts robust prophylactic nephroprotective efficacy against CP-induced acute kidney injury. This protective action is driven by the clear suppression of oxidative stress, restriction of macro-inflammatory signaling, and the direct inhibition of mitochondrial-mediated apoptotic pathways.