Hepatoprotective and Nephroprotective Effects of Leaf Extract Against Paracetamol-Induced Toxicity: Combined Mouse Model-Integrated in Silico Evidence.

Acetaminophen, or paracetamol (PCM), is a common painkiller used to treat aches, pain, and fever. Nevertheless, PCM has been reported to be hepatotoxic and nephrotoxic in humans. Thus, there is a need to identify how this side effect can be treated. Previous studies have shown that Leea species possess antioxidative, anthelmintic, anti-cytotoxic, hepatoprotective, and nephroprotective properties. However, the role of (LG) in modulating PCM-induced hepatotoxicity or nephrotoxicity remains unknown. Herein, we investigate the possibility of leaf extract (LGE) to ameliorate PCM toxic effects, evaluate hepatic and renal function, oxidative stress markers, and safety, and perform molecular docking to predict affinities of extract compounds for their targets compared to PCM. An in vivo rat model was used for Leea guineensis extract or silymarin (SLM, standard drug) at various concentrations, and it was co-administered with PCM. We observed that extract is rich in phytochemical constituents, and its treatment in rats did not significantly affect body weight. Our data showed that PCM increased bilirubin, creatinine, uric acid, Alanine aminotransferase (ALT), and cholesterol levels but decreased Aspartate aminotransferase (AST) in plasma. Moreover, it increased lipid peroxidation (MDA) levels in the liver and kidneys, while the total protein was elevated in the latter. Interestingly, extract and SLM abrogated the elevated parameters due to PCM toxicity. Importantly, histopathological examination showed that extract demonstrated the potential to ameliorate hepatic and renal lesions caused by PCM intoxication, thus demonstrating its safety. Furthermore, comparative molecular binding affinities of the study ligands binding the target corroborate the experimental findings. Our study shows that leaf extract, through its rich phytochemicals, can protect the liver and kidneys against the toxic effects of paracetamol in a dose-dependent manner.