Bile acids are toxic for isolated cardiac mitochondria: a possible cause for hepatic-derived cardiomyopathies?
Cholestasis and other liver diseases may affect the heart through the toxic effects of the retained bile acids on cardiac mitochondria, which could explain the origin of hepatic-derived cardiomyopathies. The objective of this work was to test the hypothesis that bile acids are toxic to heart mitochondria for concentrations that are relevant for cholestasis. Heart mitochondria were isolated from rat and subjected to incubation with selected bile acids (litocholic acid [LCA], deoxycholic acid [DCA], chenodeoxycholic acid [CDCA], glycochenodeoxycholic acid [GCDC], taurodeoxycholic acid [TDCA], and glycoursodeoxycholic acid [GUDC]). We observed that the most toxic bile acids were also the most lipophilic ones (LCA, DCA, and CDCA), inducing a decrease on state 3 respiration, respiratory control ratio, and membrane potential and causing the induction of the mitochondrial permeability transition. GUDC was the bile acid with lower indexes of toxicity on isolated heart mitochondria. The results of this research indicate that at toxicologically relevant concentrations, most bile acids (mainly the most lipophilic) alter mitochondrial bioenergetics. The impairment of cardiac mitochondrial function may be an important cause for the observed cardiac alterations during cholestasis.
Ferreira
Manuela
M
Centro de Neurociências e Biologia Celular de Coimbra, Dept. Zoologia, Faculdade de Ciências e Tecnologia, Universidade de Coimbra, P-3004-517 Coimbra, Portugal.
Coxito
Pedro M
PM
Sardão
Vilma A
VA
Palmeira
Carlos M
CM
Oliveira
Paulo J
PJ
D000818:Animals; D001647:Bile Acids and Salts / Q000633:toxicity*; D009202:Cardiomyopathies / Q000139:chemically induced* / Q000503:physiopathology; D056486:Chemical and Drug Induced Liver Injury; D066298:In Vitro Techniques; D008107:Liver Diseases / Q000503:physiopathology; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
D001647:Bile Acids and Salts