epidermal-growth-factor and Substance-Withdrawal-Syndrome

To examine whether the reversibility of chronic cyclosporine A (CsA) nephrotoxicity is associated with apoptotic cell death and its regulatory factors.. 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.. 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.. 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.

Topics: Animals; Apoptosis; Cyclosporine; Epidermal Growth Factor; Fas Ligand Protein; Kidney; Kidney Diseases; Male; Membrane Glycoproteins; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Sprague-Dawley; RNA, Messenger; Substance Withdrawal Syndrome; Transforming Growth Factor beta; Transforming Growth Factor beta1