Effect of dietary α-linolenate/linoleate balance on endotoxin-induced hepatitis in mice

Mice were fed diets with three different ratios of α-linolenate (18:-3) to linoleate (18:2n-6), and the severity of hepatitis during endotoxic shock was compared. Dietary enrichment with α-linolenate increased the severity of hepatitis and the mortality induced by lipopolysaccharide (LPS) in combination with D-galactosamine (GalN). Differences in the dietary α-linolenate/linoleate balance were mainly reflected in the levels of arachidonate and eicosapenatenoate in liver phospholipids. Pretreatement 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 α-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.