Oltipraz Ameliorizing the Oxidation and Hepatotoxicity Induced by the Anticancer Drug, Tamoxifen in Female Rats

Although tamoxifen has been under clinical investigation as a chemopreventive agent against breast cancer for at least a decade, yet its use is still debatable, since it showed to be able to induce liver tumor. Oltipraz as an organosulpher compound, naturally found in cruciferous plants was originally developed as an antischistosomal agent and showed to possess chemopreventive activity against different classes of carcinogens. Female Sprague Dawely rats were orally supplemented with tamoxifen (200 mg/kg body wt.) and oltipraz (30 mg/kg body wt.) daily up to 28 days. Blood samples were taken after one and 4 weeks of administration. The data revealed that tamoxifen administration resulted in significant increases in serum alkaline phosphatase (ALP), gammaglutamyl transferase (gGT) and lactate dehydrogenase (LDH) activity levels indicating liver dysfunction, decreased levels of glutathione (GSH) indicating antioxidant depression associated with increased malondialdehyde, MDA (lipid peroxidation) and carbonyl (protein oxidation). The changes in the assayed parameters indicate dose and time dependent effect. Oltipraz alone caused non-significant changes in the assayed parameters except for the significant increase in GSH content indicating its safe use. The group of rats receiving both drugs showed changes in the assayed parameters less intensified than those recorded in rats received tamoxifen without oltipraz indicating a beneficial role of oltipraz in hindering the side toxic effects of tamoxifen