Nephroprotective Effects of Wedelolactone against Snake Venom-Induced Acute Kidney Injury: Insights into Experimental Envenomation

Snakebite-induced acute kidney injury (sAKI) is a severe clinical complication associated with Bothrops envenomation that can lead to kidney failure. Alternative therapies are needed due to the limitations of antivenom, including variable efficacy, risk of adverse reactions, and significant barriers to access, such as long distances, transportation difficulties, and high costs. This study evaluates the nephroprotective effects of wedelolactone (WEL), a bioactive coumestan derived from Eclipta prostrata, known for its anti-inflammatory and antioxidant properties, in a preclinical model of sAKI. Wistar rats were intramuscularly administered 3.5 mg/kg Bothrops jararacussu (Bj) venom to induce sAKI, followed by treatment with WEL (2, 5, or 10 mg/kg) 2 h postenvenomation. At 5 mg/kg, WEL effectively mitigated kidney dysfunction, preserving the glomerular filtration rate and reducing proteinuria. Histological analysis revealed a preserved kidney cytoarchitecture and reduced collagen deposition. Biochemical assays indicated that WEL reduced matrix metalloproteinase activity and nitrite levels, key mediators of Bj-induced nephrotoxicity, suggesting a protective role via antioxidant mechanisms. However, WEL at 2 or 5 mg/kg did not prevent Bj-induced muscle damage. Additionally, the 10 mg/kg dose of WEL administered to Bj rats was associated with kidney injury, limiting its potential for clinical application. Notably, WEL did not impair kidney function in healthy rats. These findings underscore the translational potential of WEL as a complementary therapeutic approach for managing sAKI and reducing the long-term burden of snakebite-related kidney disease.