Lipid peroxidation in acrylonitrile-treated rats, evidenced by elevated ethane production.
The intraperitoneal administration of acrylonitrile (greater than 25 mg kg-1) to rats is associated with an increased production of ethane and a rise of the serum activity of the cytosolic enzyme, sorbitol dehydrogenase. These effects are prevented by pretreatment with vitamin E and the microsomal enzyme inhibitor SKF 525A, but are exacerbated by pretreatment with the microsomal enzyme inducer, phenobarbital. Repeated intraperitoneal administration of acrylonitrile (40 mg kg-1) for four weeks also increases ethane production and serum SDH activity, and produces various morphological changes in liver parenchymal cells (necrosis, increased mitotic activity, increased nucleolar size and myelinic figures in mitochondria) and inhibits the growth of the animals. All these effects are prevented by the administration of vitamin E (190 mg kg-1 i.p., daily) during the last two weeks of treatment. A dose of sodium cyanide (2.5 mg kg-1 i.p.) which leads to a urinary excretion of thiocyanate similar to that found after the intraperitoneal administration of 25 mg kg-1 acrylonitrile, does not stimulate ethane production. This study suggests that the hepatoxicity of acrylonitrile may, at least partly, result from a lipoperoxidation process and is linked with its microsomal oxidative biotransformation.
Ivanov
V
V
Unité de Toxicologie Industrielle et Médecine, Catholic University of Louvain, Brussels, Belgium.
Rahier
J
J
Lauwerys
R
R
D000181:Acrylonitrile / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004980:Ethane / Q000378:metabolism*; D007263:Infusions, Parenteral; D007064:L-Iditol 2-Dehydrogenase / Q000097:blood; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000473:pathology; D008297:Male; D009570:Nitriles / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D009570:Nitriles; D007064:L-Iditol 2-Dehydrogenase; D004980:Ethane; D000181:Acrylonitrile