Comparison of the effects of carbon tetrachloride and of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the disposition of linoleic acid in rat liver in vitro.
Both 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and carbon tetrachloride (CCl4) have conspicuous effects on lipid metabolism in rat liver. Although it is generally accepted that CCl4 administration leads to hepatic lipid peroxidation in vivo, conflicting reports from different laboratories make it unclear whether or not lipid peroxidation is involved in the mechanism of toxicity of TCDD. The present study involved pretreating F344 rats with CCl4 or TCDD, then at predetermined times thereafter, giving [U-14C]linoleic acid. A variety of compound classes were monitored in extracts of liver taken 30 min after the label was given. A previously unreported effect of CCl4 was a conspicuous increase in turnover of 1,2-diglycerides. That CCl4 did cause lipid peroxidation was evident from the presence of allylic hydroxyacids not seen in vehicle-treated controls, greatly increased radioactivity in protein-bound material, and decreased levels of arachidonate without decreased synthesis from linolate. Where effects of TCDD pretreatment could be seen, they were much less than the corresponding effects of CCl4. No allylic hydroxyacids were detected in livers of TCDD-treated rats. The concentration of arachidonate was not reduced, and elongation of linolate was not stimulated, indicating that TCDD did not cause extensive-but-repaired peroxidation. It is concluded that while TCDD may slightly increase hepatic lipid peroxidation in rats in vivo, the extent of such stimulation appears to be too slight to account for the toxicity of TCDD.
D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002250:Carbon Radioisotopes; D002251:Carbon Tetrachloride / Q000494:pharmacology*; D002855:Chromatography, Thin Layer; D004147:Dioxins / Q000494:pharmacology*; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D007700:Kinetics; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000378:metabolism*; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344
D000447:Aldehydes; D001095:Arachidonic Acids; D002250:Carbon Radioisotopes; D004147:Dioxins; D005227:Fatty Acids; D008041:Linoleic Acids; D008054:Lipid Peroxides; D000072317:Polychlorinated Dibenzodioxins; D016718:Arachidonic Acid; D019787:Linoleic Acid; D002251:Carbon Tetrachloride; C027576:4-hydroxy-2-nonenal