RESUMO
Sporadic inclusion body myositis (sIBM) is the most common idiopathic inflammatory myopathy, and several reports have suggested that mitochondrial abnormalities are involved in its etiology. We recruited 9 sIBM patients and found significant histological changes and an elevation of growth differential factor 15 (GDF15), a marker of mitochondrial disease, strongly suggesting the involvement of mitochondrial dysfunction. Bioenergetic analysis of sIBM patient myoblasts revealed impaired mitochondrial function. Decreased ATP production, reduced mitochondrial size and reduced mitochondrial dynamics were also observed in sIBM myoblasts. Cell vulnerability to oxidative stress also suggested the existence of mitochondrial dysfunction. Mitochonic acid-5 (MA-5) increased the cellular ATP level, reduced mitochondrial ROS, and provided protection against sIBM myoblast death. MA-5 also improved the survival of sIBM skin fibroblasts as well as mitochondrial morphology and dynamics in these cells. The reduction in the gene expression levels of Opa1 and Drp1 was also reversed by MA-5, suggesting the modification of the fusion/fission process. These data suggest that MA-5 may provide an alternative therapeutic strategy for treating not only mitochondrial diseases but also sIBM.
Assuntos
Ácidos Indolacéticos/uso terapêutico , Mitocôndrias Musculares/metabolismo , Miosite de Corpos de Inclusão/tratamento farmacológico , Fenilbutiratos/uso terapêutico , Trifosfato de Adenosina/biossíntese , Idoso , Idoso de 80 Anos ou mais , Butionina Sulfoximina/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , DNA Mitocondrial/genética , Avaliação Pré-Clínica de Medicamentos , Dinaminas/biossíntese , Dinaminas/genética , Feminino , Fatores de Crescimento de Fibroblastos/sangue , Fibroblastos/efeitos dos fármacos , GTP Fosfo-Hidrolases/biossíntese , GTP Fosfo-Hidrolases/genética , Fator 15 de Diferenciação de Crescimento/biossíntese , Fator 15 de Diferenciação de Crescimento/sangue , Fator 15 de Diferenciação de Crescimento/genética , Humanos , Ácidos Indolacéticos/farmacologia , Masculino , Pessoa de Meia-Idade , Mitocôndrias Musculares/patologia , Mioblastos/efeitos dos fármacos , Mioblastos/metabolismo , Mioblastos/ultraestrutura , Miosite de Corpos de Inclusão/metabolismo , Miosite de Corpos de Inclusão/patologia , Consumo de Oxigênio , Fenilbutiratos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Estudos RetrospectivosRESUMO
We report a case of a 67-year-old woman with hypokalemic rhabdomyolysis induced by pseudohyperaldosteronism. The pseudohyperaldosteronism in this case was caused by the administration of a traditional Chinese medicine, which contained 2.0 g of licorice in the approved daily dose. She started to suffer from hypertension and general fatigue after taking the medication, but continued it for two years until admission after an episode of diarrhea and vomiting. On admission, severe hypokalemia (1.6 mEq/L) and increased serum creatinine kinase (8,778 IU/L) was noted. With the findings of a high transtubular potassium concentration gradient (TTKG) in spite of low plasma renin activity and a low plasma aldosterone concentration, we suspected licorice-induced pseudohyperaldosteronism as the cause of her hypokalemic rhabdomyolysis. The Chinese medicine was terminated, and she received appropriate hydration and potassium replacement therapy as judged by the value of TTKG with the result that her serum potassium and creatinine kinase levels were normalized without any more adverse events. Since it was only a low dose of licorice (2.0 g/day) that induced hypokalemic rhabdomyolysis in this case, serum electrolytes should be examined in all cases under the possible consumption of licorice.