Reduction in cardiac mitochondrial calcium loading capacity is observable during alpha-naphthylisothiocyanate-induced acute cholestasis: a clue for hepatic-derived cardiomyopathies?
Cardiovascular changes of still obscure origin are sometimes correlated with co-existing liver diseases, as cholestasis. The aim of this work was to examine and compare cardiac mitochondrial bioenergetics and calcium loading capacity from rats injected with a single dose of alpha-naphthylisothiocyanate (ANIT), a cholestasis-inducing compound. Forty-eight hours after ANIT administration, blood samples were collected and markers for hepatic disease were determined. Heart mitochondria from both control and ANIT-injected rats were isolated and subjected to biochemical characterization, including the susceptibility to the calcium-dependent permeability transition. The results showed that cardiac mitochondria from cholestatic animals did not have significant changes in respiratory parameters or in the basal levels of adenine nucleotide. The most impressive result from this work was that cardiac mitochondria from ANIT-injected animals had a lower calcium loading capacity. The prevention of this property by cyclosporin-A, a specific inhibitor of the mitochondrial permeability transition, showed that this phenomenon was reason for the reduced calcium loading capacity in ANIT-injected animals. The results suggest that, during the development of ANIT-induced cholestasis, heart mitochondria loose their default ability to buffer calcium. Our results may contribute to explain the occurrence of cardiomyopathies sometimes associated with cholestatic disease.
Oliveira
Paulo J
PJ
Centro de Neurociências de Coimbra, Unidade de Investigação Básica em Cardiologia, Instituto de Investigação em Luz e Imagem, Universidade de Coimbra, Azinhaga de Sta. Conbra, P-3000-354, Coimbra, Portugal. pauloliv@ci.uc.pt
Rolo
Anabela P
AP
Seiça
Raquel
R
Santos
Maria S
MS
Palmeira
Carlos M
CM
Moreno
António J
AJ
D015058:1-Naphthylisothiocyanate; D000208:Acute Disease; D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D009202:Cardiomyopathies / Q000209:etiology*; D002779:Cholestasis / Q000139:chemically induced / Q000150:complications / Q000378:metabolism*; D004734:Energy Metabolism; D005260:Female; D007473:Ion Channels / Q000378:metabolism*; D008564:Membrane Potentials; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D051381:Rats; D017208:Rats, Wistar
D007473:Ion Channels; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D015058:1-Naphthylisothiocyanate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D002118:Calcium