|
The effects of 5 novel hepatotrophic agents, dithiol malonate derivatives (DMDs; DMD1-DMD5), on the liver microsomal lipid peroxidation induced by carbon tetrachloride (CCl_4) and the correlations with the changes of microsomal electron transport system were investigated. All DMDs were found to inhibit the lipid peroxidation induced by CCl_4 in mice and rats as well in vitro liver microsomal system. Therefore, each DMD seemed to have direct mode of action on liver microsomes to inhibit the lipid peroxidation. As an ex vivo study, the induced lipid peroxidation by CCl_4 and the changes in electron transport system were determined with liver microsomes obtained from rats chronically treated with DMDs for 7 days. The induced lipid peroxide contents in liver microsomal system were lower in DMD1, DMD2 and DMD3 treated group, but higher in DMD4 and DMD5 group when compared to the control group. Cyt. p.450 contents in the microsomes were decreased by the treatment with DMD1, DMD2 and DMD3, but increased significantly by DMD4 with great extent and by DMD5 with less extent. The cyt. p-450 isozymes induced by treatment of DMD4 and DMD5 were identified as 3-methylcholanthrene (MC) type. The NADPH cyt. -C reductase activities of the microsomes treated with DMD1, DMD2, DMD4 and DMD5 were increased in the range of around 20% to 50%, but decreased with DMD3, All DMDs increased dyt. -b_5 content and did not alter NAdH-cyt, -b_5 reductase activities in the microsomes. In summary, the 5 novel hepatotrophic agents (DMDs) markedly protected against lipid peroxidation induced by CCl_4 in vivo and in vitro possibly through the mechanism of direct action on the liver microsomes. The degree of inhibition produced by DMDs on lipid peroxidation induced by CCl_4 seemed to coincide rather with cyt. p-450 contents than with other components of liver microsomal electron transport system including NADPH-cyt, -C reductase.
|