Effect of dietary alpha-linolenate/linoleate balance on endotoxin-induced hepatitis in mice.
Mice were fed diets with three different ratios of alpha-linolenate (18:3n-3) to linoleate (18:2n-6), and the severity of hepatitis during endotoxic shock was compared. Dietary enrichment with alpha-linolenate increased the severity of hepatitis and the mortality induced by lipopolysaccharide (LPS) in combination with D-galactosamine (GalN). Differences in the dietary alpha-linolenate/linoleate balance were mainly reflected in the levels of arachidonate and eicosapenatenoate in liver phospholipids. Pretreatment of mice with indomethacin was found to also enhance the severity of GalN/LPS-hepatitis. This indicated that cyclooxygenase products of arachidonate may suppress the development of GalN/LPS-hepatitis. The enhancement by high alpha-linolenate diets was not observed when a lethal dose of LPS in the absence of GalN was given. Our results indicate that there are pathophysiological conditions of endotoxin-induced hepatitis under which cyclooxygenase products of arachidonate play protective roles.
Watanabe
S
S
Department of Biological Chemistry, Faculty of Pharmaceutical Sciences, Nagoya City University, Japan.
Okuyama
H
H
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000503:physiopathology*; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage / Q000494:pharmacology*; D015118:Eicosapentaenoic Acid / Q000378:metabolism; D005688:Galactosamine / Q000633:toxicity; D007213:Indomethacin / Q000494:pharmacology; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D008042:Linolenic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D010743:Phospholipids / Q000378:metabolism; D017962:alpha-Linolenic Acid
D001095:Arachidonic Acids; D004042:Dietary Fats, Unsaturated; D008041:Linoleic Acids; D008042:Linolenic Acids; D008070:Lipopolysaccharides; D010743:Phospholipids; D017962:alpha-Linolenic Acid; D016718:Arachidonic Acid; D005688:Galactosamine; D019787:Linoleic Acid; D015118:Eicosapentaenoic Acid; D007213:Indomethacin