Protective effect of diazoxide against antimycin A-induced mitochondrial dysfunction in osteoblastic MC3T3-E1 cells

Abstract

Treatment of various types of cells with diazoxide has been shown to precondition cells to subsequent injuries and inhibit cell death. In this study, the protective effects of diazoxide against pharmacological inhibition of the respiratory chain were studied using osteoblastic MC3T3-E1 cells treated with antimycin A (AMA), which inhibits complex III of the electron transport system. Diazoxide restored mitochondrial membrane potential dissipation, inactivation of complex IV, ATP loss, and intracellular calcium elevation that was induced by AMA treatment, and prevented cell death. The results imply that diazoxide protects osteoblasts from AMA-induced cell death via improved mitochondrial function. Moreover, diazoxide scavenged mitochondrial superoxide anions generated by AMA, and prevented nitrotyrosine increase and thioredoxin reductase inactivation induced by AMA, suggesting that diazoxide may be useful to protect mitochondria from a burst of oxidative stress. Our results demonstrate that diazoxide may reduce or prevent osteoblasts degeneration in osteoporosis.