Background: Heavy metals such as lead are considered a toxicant that can cause multiple organ complications including cancer, liver disease, renal diseases, neurodegenerative diseases, and reproductive diseases. In pursuit of a low-cost and easily accessible antidote, this research examined the role of Pericopsis laxiflora extract in acute lead poisoning in Sprague-Dawley rats. Methods: Liver damage was caused in animal studies by inducing lead acetate (50 mg/kg daily, intraperitoneally (i.p.), 7 days following treatment of rats with hydroethanolic stem bark extract (HSE) and methanolic stem bark extract (MSE) and Silymarin orally for one week. The study assessed the liver protective effects of extracts containing alkaloids, polyphenols, flavonoids, and tannins by evaluating changes in body and organ weights, serum biochemical markers, antioxidative and oxidative stress biomarkers, pro-inflammatory cytokines, and histopathological findings. Results: Rats exposed to Pb(Ac)2 exhibited significant alterations in various parameters, and co-treatment with HSE or MSE effectively normalized these biomarkers. Histopathological analysis confirmed the protective impact of HSE and MSE against Pb(Ac)2-induced liver damage, with HSE demonstrating the highest level of liver protection. Conclusion: These findings indicate that hydroethanolic and methanolic extracts of Pericopsis laxiflora stem bark have hepatoprotective, anti-inflammatory, and antioxidative properties against Pb(Ac)2-induced toxicity and may be explored as potential agents for drug-induced liver diseases. Keywords: Antioxidant; Hepatotoxicity; Histopathology; Inflammation; Pericopsis laxiflora
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