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Toxicol."],"published-print":{"date-parts":[[1990,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The ability of two novel antioxidants, U\u201074,006F and U\u201078,517G, as well as the known antioxidant <jats:italic>N,N<\/jats:italic>\u2032\u2010diphenyl\u2010<jats:italic>p<\/jats:italic>\u2010phenylenediamine to inhibit lipid peroxidation induced by carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>) was investigated in Aroclor 1254\u2010induced rat hepatic microsomes. All three compounds completely inhibited lipid peroxidation in microsomes as measured by the formation of thiobarbituric acid reactive substances (TBARS). Inhibition of lipid peroxidation was not a function of decreased bioactivation of CCl<jats:sub>4<\/jats:sub>, as the compounds did not substantially inhibit benzphetamine <jats:italic>N<\/jats:italic>\u2010demethylase activity or covalent binding of [14\u2010C]CCl<jats:sub>4<\/jats:sub> to lipid or protein. Parallel studies examined the hepatoprotective effects of the compounds <jats:italic>in vivo<\/jats:italic>. Rats were pretreated with antioxidant or vehicle prior to administration of CCl<jats:sub>4<\/jats:sub> (300 or 600 \u03bcL\/kg i.p.). Sera were collected 24 h postadministration of CCl<jats:sub>4<\/jats:sub> and analyzed for alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities and total bilirubin. Administration of CCl<jats:sub>4<\/jats:sub> produced elevations in ALT, moderate changes in bilirubin, and no change in ALP activities. Histological examination of CCl<jats:sub>4<\/jats:sub>\u2010treated livers revealed lipidosis and centrilobular necrosis. The antioxidants partially improved the clinical chemistry parameters, but had minimal effects on the histological lesion. In contrast to the complete inhibition of lipid peroxidation observed in the <jats:italic>in vitro<\/jats:italic> studies, none of the antioxidants markedly protected against CCl<jats:sub>4<\/jats:sub>\u2010induced toxicity <jats:italic>in vivo<\/jats:italic>.<\/jats:p>","DOI":"10.1002\/jbt.2570050306","type":"journal-article","created":{"date-parts":[[2006,10,18]],"date-time":"2006-10-18T01:36:11Z","timestamp":1161135371000},"page":"167-174","source":"Crossref","is-referenced-by-count":14,"title":["Inhibition of carbon tetrachloride\u2010induced lipid peroxidation by novel antioxidants in rat hepatic microsomes: Dissociation from hepatoprotective effects <i>in vivo<\/i>"],"prefix":"10.1002","volume":"5","author":[{"given":"G. H. I.","family":"Wolfgang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. A.","family":"Jolly","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W. 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