Cisplatin is a widely used chemotherapeutic drug in the treatment of various solid tumors. However, the cisplatin-induced acute\nkidney injury remains a disturbing complication, which still lacks effective prevention. Cisplatin-induced oxidative damage and\nmitochondrial dysfunction are anticipated to be crucial in the occurrence of kidney injury. Astragalus polysaccharide (APS) has\nbeen reported to possess multiple biological activities including anti-inflammatory, antioxidant, and mitochondria protection. In\nthis study, we investigated the potentially protective effect of APS against cisplatin-induced kidney injury both in vivo and in vitro.\nWe found that APS pretreatment attenuated the cisplatin-induced renal dysfunction and histopathological damage in mice; in\naddition, it also protected the viability of HK-2 cells upon cisplatin exposure. APS attenuated the cisplatin-induced oxidative\ndamage by reducing reactive oxygen species (ROS) generation and recovering the activities of total superoxide dismutase and\nglutathione peroxidase in mice kidney. In addition, electron microscope analysis indicated that cisplatin induced extensive\nmitochondrial vacuolization in mice kidney. However, APS administration reversed these mitochondrial morphology changes. In\nHK-2 cells, APS reduced the cisplatin-induced mitochondrial and intracellular ROS generation. Furthermore, APS protected the\nnormal morphology of mitochondria, blocked the cisplatin-induced mitochondrial permeability transition pore opening, and\nreduced the cytochrome c leakage. Subsequently, APS reduced the cisplatin-induced apoptosis in mice renal and HK-2 cells. In\nconclusion, our data suggested that APS pretreatment might prevent cisplatin-induced kidney injury through attenuating\noxidative damage, protecting mitochondria, and ameliorating mitochondrial-mediated apoptosis.
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