Cyclosporin and tacrolimus do not potentiate oxidative damage in pulmonary epithelial cells.
Oxidative stress can lead to cellular injury and apoptosis within the pulmonary allograft. We investigated the effects of oxidative damage on the growth and survival of cultured human pulmonary epithelial cells treated with hydrogen peroxide (H(2)O(2)) in the presence and absence of cyclosporin A (CsA) and tacrolimus. Treatment of A549 cells with 1 mmol/l H(2)O(2) for 48 h led to a 39% decrease in cell growth. Treatment with 500 ng/ml CsA for 48 h reduced cell survival by 68%, and treatment with 30 ng/ml tacrolimus reduced cell survival by 32%. The addition of CsA or tacrolimus to cells grown in H(2)O(2) did not further diminish cell survival. These studies demonstrated that H(2)O(2), CsA, and tacrolimus treatments decrease survival of pulmonary epithelial cells. However, CsA and tacrolimus do not further potentiate H(2)O(2)-induced toxicity.
Mogayzel
Peter J
PJ
Eudowood Division of Pediatric Respiratory Sciences, The Johns Hopkins Hospital, 600 North Wolfe Street, Park 316, Baltimore MD 21287, USA. mogayzel@mail.jhmi.edu
Wagner
Traci L
TL
D000230:Adenocarcinoma; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D016572:Cyclosporine / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008175:Lung Neoplasms; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D020545:Respiratory Mucosa / Q000187:drug effects / Q000502:physiology*; D016559:Tacrolimus / Q000494:pharmacology*
D016572:Cyclosporine; D006861:Hydrogen Peroxide; D016559:Tacrolimus