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 G(0)/G(1) cell cycle arrest even at its maximal protective concentration (30 microM), whereas vitamin E almost completely inhibited both CsA-induced apoptosis and cell cycle arrest at 1 microM concentration. In addition, Pd reduced the amount of CsA-induced ROS and showed partly restored catalase which was down-regulated by 10 microM CsA at both the mRNA and protein levels. Vitamin E completely abolished CsA-induced ROS generation and catalase attenuation at 10 microM concentration. Finally, the effects of 1 microM vitamin E on CsA-induced ROS and apoptosis as well as cell cycle arrest were similar to those of 30 microM 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.
Jeon
Seung Hyun
SH
Department of Urology, School of Medicine, Kyung Hee University, Seoul 130-702, Republic of Korea.
Piao
Yu Ji
YJ
Choi
Kyu Jin
KJ
Hong
Feng
F
Baek
Haeng Woon
HW
Kang
Insug
I
Ha
Joohun
J
Kim
Sung Soo
SS
Chang
Sung-Goo
SG
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002374:Catalase / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D016572:Cyclosporine / Q000633:toxicity*; D004285:Dogs; D015536:Down-Regulation / Q000187:drug effects; D004347:Drug Interactions; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011239:Prednisolone / Q000494:pharmacology*; D017382:Reactive Oxygen Species; D014810:Vitamin E / Q000494:pharmacology
D017382:Reactive Oxygen Species; D014810:Vitamin E; D016572:Cyclosporine; D011239:Prednisolone; D002374:Catalase