MECHANISM OF BILE ACID-INDUCED HEMOLYSIS

Abstract

Hemolysis associated with liver disease may be partly induced by bile acids (BA). Since it occurs at concentrations below BA CMC's, it is probably not entirely due to RBC membrane solubilization. We studied the hemolytic effect of two cytotoxic (lithocholic acid sulfate and glucuronide (LCS, LCG)), and two non-cytotoxic (taurolithocholic acid sulfate and taurocholic acid (TLCS, TC)) BA's on human RBC's (0.75 μM BA, HEPES buffer, pH 7.4, 37°). LCS and LCG increased hemolysis over controls by 200-500%; TLCS and TC had no significant effect. Presence of calcium (Ca) chelator EDTA reduced hemolysis by LCS by one-half, and completely blocked LCG-induced hemolysis. ⁴⁵Ca uptake by RBC's exposed to LCS increased 40 × over controls, and further increased 3-fold by the addition of Stelazine, 1 μM, a known inhibitor of RBC Ca efflux. Neither TC nor Stelazine alone affected uptake. Conclusions: (1) LCS and LCG have a selective hemolytic effect not exhibited by TLCS and TC; (2) this hemolysis is prevented by EDTA and is associated with ⁴⁵Ca uptake. Working hypotheses: (1) In view of the known relations between cell toxicity and Ca uptake, BA-induced hemolysis may be Ca mediated; (2) cytotoxic BA's may generate Ca-permeating channels, as has been shown for BA-exposed black lipid films; (3) RBC's may prove a readily available and easily manipulated model for the study of BA-cell interactions.

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