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 generation in vivo of dithiothreitol (DTT) from DTT tetraacetate (DTTAC) was accompanied with preventive effects against CCl4-induced necrogenic effects on the liver. In that study, we reported the ability of treatment to decrease the intensity of covalent binding (CB) of the CCl4 reactive metabolites to cellular components but no evidence of preventive effects on CCl4-induced lipid peroxidation (LP) was obtained by the diene hyperconjugation technique. Now, we report that DTT at concentrations 1 or 3 mM inhibit at steps of the process after diene conjugation and prior to malondialdehyde formation. One of those steps might involve peroxides since we observed that DTT is able to significantly react with benzoyl peroxide in a model system. Others might also involve free radicals for in the present study we observed the reaction of DTT with trichloromethyl or trichloromethylperoxy free radicals generated from CBrCl3 in a model system. Reactions of DTT with free radicals and peroxides resulting in inhibition of CB and LP might be critical components in the preventive effects of DTTAC against CCl4-induced liver damage.
de Mecca
M M
MM
Centro de Investigaciones Toxicológicas (CEITOX) CITEFA/CONICET, Pcia. de Buenos Aires, Argentina.
Castro
G D
GD
Díaz Gómez
M I
MI
Castro
J A
JA
D000818:Animals; D002251:Carbon Tetrachloride / Q000378:metabolism / Q000633:toxicity*; D004229:Dithiothreitol / Q000494:pharmacology*; D005609:Free Radicals; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D009249:NADP / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D005609:Free Radicals; D009249:NADP; D002251:Carbon Tetrachloride; D004229:Dithiothreitol