Biochemical and Molecular Insights Into Monocrotaline‐Induced Hepatotoxicity: An Experimental Mouse Study

Monocrotaline (MCT), a plant-derived pyrrolizidine alkaloid, is well known for its hepatotoxic effects. However, full elucidation of the mechanisms underlying MCT-induced hepatotoxicity, as well as the development of reliable biomarkers for early detection and monitoring, requires an integrated evaluation of biochemical, molecular, and histopathological data. This study aims to evaluate the hepatotoxic effects of MCT using biochemical, molecular, and histopathological data. Thirty male BALB/c mice were randomly assigned to three groups: control, acute toxicity, and subacute toxicity. The control group received saline, the acute group received a single dose of 120 mg/kg MCT, and the subacute group received the same dose administered three times at 5-day intervals. Blood and liver tissues were collected for biochemical and oxidative stress analysis. Apoptotic markers were evaluated at the protein and gene expression levels using ELISA, qPCR, and PCR array. Histopathological examination was performed to assess structural liver alterations. MCT significantly increased hepatic enzyme levels including ALT, GGT, and TBIL, while AST levels showed a nonsignificant numerical increase and were associated with disrupted lipid and protein metabolism, evidenced by increased TCHO and decreased TP. Oxidative stress markers (TOS, OSI) increased in the acute group with reduced TAS, whereas TAS increased in the subacute group, indicating temporal modulation of antioxidant defenses. Bax and caspase-3 were upregulated, and Bcl-2 was downregulated at the protein level. qPCR corroborated these findings at the transcriptional level, although without statistical significance. Histopathological analysis revealed extensive hepatic injury, particularly in the acute toxicity group. The findings indicate that MCT induces liver injury via enzymatic dysregulation, oxidative stress, and apoptosis and highlight the need for further research to identify reliable biomarkers for the early detection and monitoring of MCT-induced hepatotoxicity.