Calcitriol attenuates the cytotoxicity induced by aluminium phosphide via inhibiting mitochondrial dysfunction and oxidative stress in rat isolated cardiomyocytes

Abstract

These days, poisoning with aluminium phosphide (AlP), is one of the main health threats in human societies. Previous studies have been reported that cardiotoxicity induced by AlP, via mitochondrial dysfunction and oxidative stress is the main cause of death in victims. On the other, collectively, multiple lines of evidence strongly suggest that calcitriol has mitochondrial protective and antioxidant effects. Therefore, we assumed that calcitriol could presumably ameliorate AlP-induced oxidative stress and mitochondrial dysfunction in cardiomyocytes. Mitochondria and cardiomyocytes were isolated by differential centrifugation and collagenase perfusion respectively from rat heart. The isolated cardiomyocytes and mitochondria were cotreated with different concentrations of calcitriol (0.2, 0.4 and 1 μg/ml) and AlP (20 μg/ml) for 3 h. The parameters of cellular toxicity including; cytotoxicity, reactive oxygen species (ROS) formation, malondialdehyde (MDA) level, mitochondria membrane potential (ΔΨm) collapse, lysosomal membrane integrity, the level of oxidized and reduced glutathione (GSH and GSSG), and mitochondrial toxicity parameters including; succinate dehydrogenase (SDH) activity and mitochondrial swelling were analyzed using biochemical and flow cytometric evaluations. Administration of AlP significantly increased cytotoxicity, GSH depletion, cellular ROS formation, MDA level, mitochondrial and lysosomal dysfunction in isolated cardiomyocytes. In isolated mitochondria, AlP decreased SDH activity and mitochondrial swelling. The cotreatment of isolated cardiomyocytes and mitochondria with calcitriol (0.4 and 1 μg/ml) and AlP (20 μg/ml) showed the ability to reduce the toxic effects of AlP. These findings suggest a potential therapeutic role of calcitriol in protecting cardiomyocytes and cardiac mitochondria from oxidative damage induced by AlP. According to the results, calcitriol exerted ameliorative effects against AlP-induced cytotoxicity and mitochondrial toxicity, and the effect was attributed to the antioxidant properties.