Prednisolone suppresses cyclosporin A-induced apoptosis but not cell cycle arrest in MDCK cells

Cyclosporin A (CsA) is a potent immunosuppressive agent, and can cause severe adverse effects including nephrotoxicity partly due to generation of reactive oxygen species (ROS). Glucocorticoids, which are widely used in combination with CsA, have been shown to reduce oxidative injuries in various cells, but its mechanism is not understood well. To investigate the effects of prednisolone (Pd) on CsA-induced cellular damage and ROS generation in Madin-Darby canine kidney (MDCK) tubular epithelial cells, cells were treated with CsA, CsA plus Pd, or CsA plus vitamin E. Pretreatment with Pd protected cells from CsA-induced apoptosis but not from G0/G1 cell cycle arrest even at its maximal protective concentration (30 μM), whereas vitamin E almost completely inhibited both CsA-induced apoptosis and cell cycle arrest at 10 μM concentration. In addition, Pd reduced the amount of CsA-induced ROS and showed partly restored catalase which was down-regulated by 10 μM CsA at both the mRNA and protein levels. Vitamin E completely abolished CsA-induced ROS generation and catalase attenuation at 10 μM concentration. Finally, the effects of 1 μM vitamin E on CsA-induced ROS and apoptosis as well as cell cycle arrest were similar to those of 30 μM Pd. We conclude that, in MDCK cells, Pd protects against CsA-induced cytotoxicity by suppressing ROS generation, although its protective effect is weaker than that of vitamin E.