Exploring the Nephroprotective Efficacy of Leucaena leucocephala Seeds in Mitigating Cisplatin-Induced Renal Damage

Abstract

Objectives: The study aimed to evaluate the nephroprotective effects of the methanolic extract of Leucaena leucocephala seeds against Cisplatin-Induced Nephrotoxicity (CIN) in rats through biochemical, antioxidant and histopathological assessments. Materials and Methods: 2 experimental models were employed, using 30 Wistar rats in each model, divided into 5 groups of 6 animals each. In Model 1, the normal control group received normal saline (10 mL/kg, p.o.), the disease control group received cisplatin (2 mg/kg, i.p.) on alternate days, the standard group was treated with Vitamin E (250 mg/kg, p.o.) and the test groups were administered Leucaena leucocephala methanolic extract at doses of 250 mg/kg and 500 mg/kg. Model 2 followed the same group allocation, but the disease control group received a single dose of cisplatin (8 mg/ kg, i.p.). Results: In both models, cisplatin administration caused significant nephrotoxicity, characterized by elevated serum creatinine, urea, uric acid, Blood Urea Nitrogen (BUN) and electrolyte levels (Na⁺, K⁺, Cl- and Ca⁺⁺). Additionally, it reduced antioxidant enzyme levels (SOD, CAT and GSH) and increased pro-inflammatory cytokines such as TNF-α. Histopathological analysis revealed marked structural damage, including tubular dilation, glomerular inflammation and disrupted renal architecture. Treatment with the methanolic extract of Leucaena leucocephala showed dose-dependent nephroprotective effects. Both doses (250 mg/kg and 500 mg/ kg) significantly reduced renal function markers, improved antioxidant enzyme levels and decreased pro-inflammatory cytokines. Histological improvements were evident, with reduced inflammation, tubular dilation and preservation of glomerular and tubular structures, especially at the higher dose of 500 mg/kg. Conclusion: These findings suggest that the methanolic extract of Leucaena leucocephala effectively mitigates cisplatin-induced nephrotoxicity by normalizing biochemical markers, enhancing antioxidant defense and protecting renal histology. The study highlights its potential as a natural therapeutic agent for managing cisplatin-induced renal damage.