Gnetum gnemon leaf extract as a potential therapeutic agent for nephrotoxicity against Dalton's Lymphoma Ascites (DLA)-induced mice

Melinjo (Gnetum gnemon) is traditionally known for its anti-inflammatory, antioxidant, and anticancer properties. However, its role in preventing cancer-related kidney damage is underexplored. This study examined the protective effects of Gnetum gnemon methanolic leaf extract (GGME) on DLA-induced (Dalton's lymphoma ascites) nephrotoxicity in Swiss albino mice. Two experiments were conducted using male albino mice (n = 5/group). In the acute study, Group I received PBS (control) and Group II received GGME (2000 mg/kg) for 14 days. In the chronic study, Group I was control, Group II -DLA-induced, Group III- DLA + cisplatin (2 mg/kg), Group IV- DLA + GGME (200 mg/kg), and Group V -DLA + GGME (400 mg/kg). DLA was induced by intraperitoneal injection of 1 × 10⁶ live DLA cells per mice, and the experiment continued for 21 days. Kidney function biomarkers (BUN, creatinine, uric acid), key electrolytes (Na⁺, K⁺, Ca²⁺), oxidative stress markers, and tissue histo-morphometry were evaluated. GGME showed no signs of toxicity at doses up to 2000 mg/kg. Mice in the group II (DLA-induced) exhibited significant nephrotoxicity, characterized by elevated BUN, creatinine, uric acid, altered electrolyte levels, increased oxidative stress, and notable renal tissue degeneration. GGME treatment, especially at 400 mg/kg, improved biochemical markers, restored antioxidant enzymes, and reduced MDA levels. Histology showed preserved kidney structure and reduced glomerular damage, with improvements in glomerular number, size, and capsular space. GGME exhibited dose-dependent nephroprotection in DLA-induced nephrotoxicity, likely via its antioxidant and anti-inflammatory actions, suggesting its potential as a complementary therapy for cancer-related kidney damage.