Cholesterol in acute cholestasis induced by taurolithocholic acid. A cytochemical study in transmission and scanning electron microscopy

Rats were given intravenous injections of a single dose of sodium taurolithocholate, and an almost total cholestasis appeared after 10 minutes and lasted for 3 hours after the injection; then the choleresis began again and 24 hours after the injection, normal values of bile flow were restored. Ultrastructural analysis of the liver during the acute cholestasis and the restoration phase showed, beside usual modifications found in most cases of cholestasis, the "characteristic" alterations of sodium taurolithocholate-induced cholestasis. Cytochemical procedures were used, both in transmission and in scanning electron microscopy, in order to delineate the possible participation of free cholesterol in these cellular modifications. After Williamson's reaction procedure (Williamson JR:J Ultrastruct Res 27:118, 1969), not only were cholesterol-digitonin complexes found in large numbers, both in the hepatocytic cytoplasm and in the biliary canaliculi, but also their morphologic appearance revealed several new features: dark sticks and dark lamellae, frequently adsorbed on the outer surface of crystalline clear material were observed by transmission electron microscopy, and plugs, obliterating parts of biliary canaliculi, were observed using scanning electron microscopy. These observations seem to indicate that a significant amount of free cholesterol is released into the hepatocyte cytoplasm and into canalicular lumina within a few minutes after the infection of sodium taurolithocholate, probably originating from the hepatocytic membranes, especially from those limiting the canalicular lumen. Such a drastic modification in the chemical constitution of these membranes should coincide with a marked modification of their active and passive transport ability.