Diosgenin Protects Against Kidney Injury and Mitochondrial Apoptosis Induced by 3-MCPD Through the Regulation of ER Stress, Ca2+ Homeostasis, and Bcl2 Expression

This study demonstrates that DIO exerts protective effect against kidney injury, mitochondrial dysfunction, and apoptosis through the inhibition of ER stress and the further maintenance of Ca2+ homeostasis and Bcl2 expression.

Treatment with DIO (15 mg kg-1 d-1 ) in Sprague-Dawley rats for 4-week relieves kidney injury induced by 3-MCPD (30 mg kg-1 d-1 ). In vitro, DIO (2, 6, and 8 µM) alleviates cell injury and apoptosis effectively in human embryonic kidney (HEK293) cells. DIO realizes its protective function via the regulation of endoplasmic reticulum (ER) stress and mitochondrial apoptosis pathway. Blockage of ER stress by 4-phenylbutyric acid (4-PBA), a specific ER stress antagonist, inhibits mitochondrial apoptosis, suggesting a connection between mitochondrial apoptosis and ER stress. Furthermore, the study demonstrates that the maintenance of Ca2+ homeostasis and Bcl2 expression, two main targets of ER stress, contributes to the protection role of DIO on mitochondrial-dependent apoptosis. In addition, DIO relieves the impairment of oxidative phosphorylation.