Biochemical, histological and ultrastructural studies on the ameliorative effects of chrysin on the hepatotoxicity of clonazepam in developing male albino rats

Chrysin is bioactive flavonoids that has numerous pharmacological activities and known to have hepatoprotective effect. The present study aimed to study the potential ameliorative effects of Chrysin (50 mg/kg b.wt./day) on Clonazepam (2 mg/kg b.wt./day) induced liver toxicity. Animals were divided into 4 groups, ten rats in each. Group 1 (Control group received a vehicle 1% w/v Tween 80), group 2 (received 2 mg/kg b.wt./day Clonazepam (CZP) suspended in 1% w/v Tween 80, group 3, (received 50 mg/kg b.wt./day Chrysin suspended in 1% w/v Tween 80, group 4 (received 2 mg/kg b.wt./day CZP, and Chrysin, 50 mg/kg b.wt./day). All animal groups were treated by oral gavage daily for 6 weeks starting at the first day of the experiment. The results indicated that in contrast to the control group, liver transaminases (ALT and AST), malondialdehide (MDA) and cytochrome P450 (Cyp3A4) were increased after the Clonazepam treatment, while the liver protein and the total antioxidant activity (TAA), glutathione reduced (GSH) contents and glutathione S-transferase (GSTs) activity were decreased. Also, the histological examination demonstrated that liver sections of CZP treated developing rats showed cytoplasmic vacuolation and fatty degeneration of some hepatocytes and their nuclei exhibited pyknosis and karyolysis. In addition to conspicuous distortions in the vasculatures, Kupffer cells proliferation and infiltration of lymphocyte were observed. Electron microscopic investigation of hepatocytes of CZP treated animals' revealed clear changes as mitochondrial dysfunction with loss of their cristae and compressed matrices. Also, dilatation and fragmentation of the rough endoplasmic reticulum into smaller stacks have been observed. On the other hand, marked improvement in the liver tissue against the damage displayed by CZP was recorded in biochemical, histological and ultrastructural screening of the hepatic animal sections treated with CZP+ Chrysin.