AIM: To examine whether the reversibility of chronic cyclosporine A (CsA) nephrotoxicity is associated with apoptotic cell death and its regulatory factors. METHODS: Chronic CsA nephrotoxicity was induced in Sprague-Dawley rats by administering CsA (15 mg/kg, sc) for 5 weeks, and then withdrawing it for 5 or 10 weeks. The effect of CsA withdrawal on apoptotic cell death was evaluated by an in situ TdT-mediated deoxyuridine triphosphate-biotin nick end-labeling (TUNEL) assay and the expression of pro-apoptotic [transforming growth factor-beta 1 (TGF-beta 1) and Fas] and anti-apoptotic [epidermal growth factors (EGF) and Bcl-2] factors. RESULTS: Discontinuation of CsA induced significant decreases in TUNEL-positive cells in a time-dependent manner and the reduction in TUNEL-positive cells was correlated with the tubulointerstitial fibrosis score (r=0.919, P<0.01). Upregulation of TGF-beta and Fas expression in CsA-treated rat kidneys was decreased significantly after withdrawal of CsA. In contrast, downregulated EGF and Bcl-2 expression returned to normal or supernormal levels. CONCLUSION: CsA withdrawal is associated with a decrease in apoptotic cell death and with changes in the expression of pro-apoptotic and anti-apoptotic molecules involved in renal wound repair. This may constitute one of the mechanisms underlying the reversibility of chronic CsA nephrotoxicity.
AIM: To examine whether the reversibility of chronic cyclosporine A (CsA) nephrotoxicity is associated with apoptotic cell death and its regulatory factors. METHODS: Chronic CsAnephrotoxicity was induced in Sprague-Dawley rats by administering CsA (15 mg/kg, sc) for 5 weeks, and then withdrawing it for 5 or 10 weeks. The effect of CsA withdrawal on apoptotic cell death was evaluated by an in situ TdT-mediated deoxyuridine triphosphate-biotin nick end-labeling (TUNEL) assay and the expression of pro-apoptotic [transforming growth factor-beta 1 (TGF-beta 1) and Fas] and anti-apoptotic [epidermal growth factors (EGF) and Bcl-2] factors. RESULTS: Discontinuation of CsA induced significant decreases in TUNEL-positive cells in a time-dependent manner and the reduction in TUNEL-positive cells was correlated with the tubulointerstitial fibrosis score (r=0.919, P<0.01). Upregulation of TGF-beta and Fas expression in CsA-treated rat kidneys was decreased significantly after withdrawal of CsA. In contrast, downregulated EGF and Bcl-2 expression returned to normal or supernormal levels. CONCLUSION:CsA withdrawal is associated with a decrease in apoptotic cell death and with changes in the expression of pro-apoptotic and anti-apoptotic molecules involved in renal wound repair. This may constitute one of the mechanisms underlying the reversibility of chronic CsAnephrotoxicity.
Authors: Jin Young Kim; Jung Yeon Ghee; Sun Woo Lim; Shang Guo Piao; Byung Ha Chung; Hye Eun Yoon; Hyeon Seok Hwang; Bum Soon Choi; Jin Kim; Chul Woo Yang Journal: J Korean Med Sci Date: 2012-01-27 Impact factor: 2.153
Authors: Long Ye Zhang; Jian Jin; Kang Luo; Shang Guo Piao; Hai Lan Zheng; Ji Zhe Jin; Sun Woo Lim; Bum Soon Choi; Chul Woo Yang; Can Li Journal: Korean J Intern Med Date: 2018-02-12 Impact factor: 2.884
Authors: Kang Luo; Sun Woo Lim; Yi Quan; Sheng Cui; Yoo Jin Shin; Eun Jeong Ko; Byung Ha Chung; Chul Woo Yang Journal: Oxid Med Cell Longev Date: 2019-10-17 Impact factor: 6.543