The Prophylactic Role of Graviola Leaves Extract against Diethylnitrosamine-Induced Renal Toxicity and Oxidative Stress in Male Wistar Albino Rats

Abstract

Kidney diseases are a significant global health issue, often progressing to life-threatening conditions. Diethylnitrosamine (DENA), a well-recognized environmental carcinogen, elicits renal toxicity primarily through mechanisms involving oxidative stress and inflammation. This research evaluated the prophylactic effects of graviola (Annona muricata L.) leaves extract in preventing renal toxicity and oxidative stress caused by DENA in male rats. The experimental design consisted of four distinct groups: Control, Graviola, DENA, and DENA plus Graviola. Renal function biomarkers, oxidative stress indicators, free radical parameters, and inflammatory and apoptotic markers were assessed. DENA administration significantly elevated serum concentrations of urea, creatinine, and uric acid, as well as malondialdehyde, whereas significantly reducing the total protein content and concentrations of antioxidant markers such as glutathione, superoxide dismutase, catalase, glutathione peroxidase, and total antioxidant capacity. It also significantly elevated inflammatory mediators (IL-6, TNF-α, IL-1β, and CRP) and apoptotic markers (annexin V, caspase 3, and P53) but lowered the anti-apoptotic protein BCL2. Co-administration of graviola extract significantly reversed these pathological changes by normalizing renal function markers, strengthening antioxidant defenses, and mitigating inflammation and apoptotic indicators. The findings suggest that graviola protects against DENA toxicity by reducing oxidative stress, boosting antioxidants, and suppressing inflammation and apoptosis. Graviola may emerge as a promising therapeutic candidate for preventing renal injury associated with environmental toxins like DENA.