Studies of the generalized Shwartzman reaction produced by diet. II. Feeding of fractions of oxidized cod liver oil.

By molecular distillation of oxidized cod liver oil a partial isolation of the lipid species responsible for the diet-induced generalized Shwartzman reaction in pregnant rats has been achieved. Molecular distillation produced three fractions and a residue. Qualitative and quantitative differences in each fraction were shown by determining iodine and saponification numbers and by thin layer chromatography on silicic acid. The incidence of the Shwartzman reaction was higher with fraction III than with either of the other two fractions, the residue, or the original oxidized cod liver oil. It is evident that the toxic factor or factors can be concentrated by molecular distillation. The high temperatures used in the molecular distillation destroy peroxides in the lipids. Therefore, in spite of the fact that oxidation of dietary fats is necessary to produce the reaction, peroxides in the dietary lipid are not necessary for the development of the tissue reaction. The residue fraction contains high molecular weight polymers and the incidence of the Shwartzman reaction is low in animals fed this material. It is unlikely that high molecular weight polymers are responsible for the tissue reaction. Animals that do not gain weight at a rate close to that of the normal pregnant rat do not develop the reaction. Conversion of fraction III into its ethyl esters increased the incidence of the Shwartzman reaction in two experiments. Esterification appears to "unmask" a certain amount of the active factor. The specific lipid material or materials responsible for the development of the generalized Shwartzman reaction remains to be found.