DITHIOTHREITOL INHIBITORY EFFECTS ON CARBON TETRACHLORIDE-PROMOTED NADPH-DEPENDENT LIPID-PEROXIDATION IN LIVER MICROSOMAL SUSPENSIONS

In previous studies from our laboratory evidence was provided that gen eration ira vivo of dithiothreitol (DTT) from DTT tetraacetate (DTTAC) was accompanied with preventive effects against CCl4-induced necrogen ic effects on the liver. In that study, we reported the ability of tre atment to decrease the intensity of covalent binding (CB) of the CCl4 reactive metabolites to cellular components but no evidence of prevent ive effects on CCl4-induced lipid peroxidation (LP) was obtained by th e diene hyperconjugation technique. Now, we report that DTT at concent rations 1 or 3 mM inhibit at steps of the process after diene conjugat ion and prior to malondialdehyde formation. One of those steps might i nvolve peroxides since we observed that DTT is able to significantly r eact with benzoyl peroxide in a model system. Others might also involv e free radicals for in the present study we observed the reaction of D TT with trichloromethyl or trichloromethylperoxy free radicals generat ed from CBrCl3 in a model system. Reactions of DTT with free radicals and peroxides resulting in inhibition of CB and LP might be critical c omponents in the preventive effects of DTTAC against CCl4-induced live r damage.