Bile Acid Composition Of Various Species

In relation to the importance of bile acids in host defence against endotoxins one may ask the question whether or not bile composition plays a role in the endotoxin sensitivity/resistance of various species [45], We have observed earlier that there are major differences in bile acid composition of bile obtained from sensitive (e.g., man, cow, guinea pig) and resistant species (e.g., birds, fish) [39], It is interesting to note that there is a direct correlation between endotoxin sensitivity and radiation sensitivity of various species. Perhaps the ontogeny of the production of bile acids in chickens bears relevance to the fact that chicken embryos show endotoxin sensitivity up to 11 days of age, which is the time of the initiation of bile acid synthesis in the liver. Older chicks or mature animals can only be made susceptible to endotoxin by lead acetate treatment. It is likely that bile acids function not only in the gut but also in the liver in addition to acyloxyacyl hydrolase enzyme discovered in 1989 to be active in the detoxification of bacterial endotoxins [46].

12. ENDOTOXIN INACTIVATION BY LIVER/BILE ACIDS

We have observed, as have others, that liver homogenates from healthy rats are capable of inac tivating small (microgram) quantities of endotoxins. In contrast, if the rats received lead acetate intravenously prior to the preparation of liver homogenates, no endotoxin inactivation was

Table IV Proven and presumed roles of bile acids and endotoxins in certain pathological processes.

Intestinal infections Surgical / septic shock Intestinal ischemic shock Tourniquet shock

Gastro-intestinal syndrome of radiation disease

Hepato-renal syndrome

Enteroviral infections (e.g., parvovirus)

Herpes viral infections

Psoriasis

Atherosclerosis

Endocrine disorders observed [39]. Similar results were obtained if we incubated natural bile fluid with lead acetate. Such bile solutions lost their capacity to detoxify endotoxin. It is likely that lead acetate damages the side chains that play an important role in the detergent effect of bile acids, and for this reason the modified bile acids are unable to detoxify endotoxin. This phenomenon may play a role in the lead acetate induced endotoxin sensitivity in vivo [39].

We demonstrated that after the dissociation of endotoxin by bile acids to its basic units, the detoxified material maintains the capacity to induce endotoxin tolerance [31-32]. It is possible that this observation will lead to the isolation of non-toxic endotoxin subunits, which will be able to stimulate natural resistance without toxic side effects [39].

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