Hepatotoxic effect of subacute vincristine administration activates necrosis and intrinsic apoptosis in rats: protective roles of broccoli and Indian mustard.

This study investigated the hepatotoxic effect of long-term vincristine (VCR) administration in rats and to assess if an individual or combined therapy with Indian mustard and broccoli afforded protection. Signs of hepatotoxicity, including altered liver architecture and higher serum levels of ALT and AST, were seen in VCR-treated rats. Concomitantly, the impaired antioxidant potential and higher mRNA levels of IL-12 and IL-4, which are markers of apoptosis, were seen in rat livers. VCR treatment induced hepatocyte apoptosis, shown by the up-regulation of mRNA and protein levels of 53, increased protein levels of cleaved caspase-3 and Bax, and reduced levels of intracellular ATP and BCl-2mRNA and protein. Although individual administration of mustard or broccoli partially ameliorated all these responses, the combined therapy of both extracts resulted in the maximum improvement. Thus, the long-term administration of VCR is hepatotoxic and induces apoptosis; however, the combined therapy of both extracts mitigated these effects.