In-vitro Anti-oxidant Studies and Preclinical Evaluation of the Hepatoprotective effect of Grewia asiatica in Paracetamol Induced Hepatotoxicity mice model

Hepatotoxicity can arise from various factors, including medication use (such as paracetamol and isoniazid), excessive alcohol consumption, viral infections (e.g., hepatitis), exposure to chemicals, genetic factors, autoimmune diseases, and pre-existing liver conditions. Notably, in cases of paracetamol overdose, the drug's metabolism shifts from safe conjugation pathways to oxidation by CYP450 enzymes, resulting in the formation of the toxic metabolite NAPQI. This metabolite depletes glutathione, leading to oxidative stress, lipid peroxidation, and mitochondrial dysfunction, which trigger cell death pathways and ultimately causing liver cell damage. Our research utilized an animal model to evaluate the hepatoprotective potential of the ethanolic extract of Grewia asiatica fruits against paracetamol-induced hepatotoxicity. The evaluation included various physical parameters (liver weight, body weight, and liver volume) and biochemical markers (AST, ALP, ALT, total proteins, albumin, globulin, and total bilirubin). Additionally, we assessed phenobarbitone-induced sleeping time and conducted histopathological examinations. Preliminary phytoconstituent analyses revealed that the ethanolic extract of Grewia asiatica (EEGA) contains a variety of compounds. In vitro antioxidant studies indicated significant antioxidant activity of the EEGA. In preventive studies, the extract at a dose of 1600 mg/kg exhibited notable hepatoprotective effects by decreasing levels of biochemical markers such as AST, ALT, ALP, and total bilirubin while increasing total proteins, albumin, and globulin. Treatment with EEGA at this dosage also resulted in a significant decrease in liver weight and a reduction in liver volume. The extract at both 800 mg/kg and 1600 mg/kg significantly elevated tissue glutathione (GSH) levels. Histopathological evaluations confirmed the hepatoprotective activity of the extract administered prior to paracetamol exposure. Furthermore, treatment with EEGA notably reduced phenobarbitone-induced sleeping times in paracetamol-treated animals in a dose-dependent manner, indicating the normalization of cytochrome P450 enzymes and further supporting the hepatoprotective properties of Grewia asiatica.