Dithiothreitol inhibitory effects on carbon tetrachloride-promoted NADPH-dependent lipid peroxidation in liver microsomal suspensions. 1995

M M de Mecca, and G D Castro, and M I Díaz Gómez, and J A Castro
Centro de Investigaciones Toxicológicas (CEITOX) CITEFA/CONICET, Pcia. de Buenos Aires, Argentina.

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.

UI MeSH Term Description Entries
D008297 Male Males
D008862 Microsomes, Liver Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough. Liver Microsomes,Liver Microsome,Microsome, Liver
D009249 NADP Nicotinamide adenine dinucleotide phosphate. A coenzyme composed of ribosylnicotinamide 5'-phosphate (NMN) coupled by pyrophosphate linkage to the 5'-phosphate adenosine 2',5'-bisphosphate. It serves as an electron carrier in a number of reactions, being alternately oxidized (NADP+) and reduced (NADPH). (Dorland, 27th ed) Coenzyme II,Nicotinamide-Adenine Dinucleotide Phosphate,Triphosphopyridine Nucleotide,NADPH,Dinucleotide Phosphate, Nicotinamide-Adenine,Nicotinamide Adenine Dinucleotide Phosphate,Nucleotide, Triphosphopyridine,Phosphate, Nicotinamide-Adenine Dinucleotide
D002251 Carbon Tetrachloride A solvent for oils, fats, lacquers, varnishes, rubber waxes, and resins, and a starting material in the manufacturing of organic compounds. Poisoning by inhalation, ingestion or skin absorption is possible and may be fatal. (Merck Index, 11th ed) Tetrachloromethane,Tetrachloride, Carbon
D004229 Dithiothreitol A reagent commonly used in biochemical studies as a protective agent to prevent the oxidation of SH (thiol) groups and for reducing disulphides to dithiols. Cleland Reagent,Cleland's Reagent,Sputolysin,Clelands Reagent,Reagent, Cleland,Reagent, Cleland's
D005609 Free Radicals Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. Free radicals include reactive oxygen and nitrogen species (RONS). They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. Free Radical
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015227 Lipid Peroxidation Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. Lipid Peroxidations,Peroxidation, Lipid,Peroxidations, Lipid
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus

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