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Decreased oxidized glutathione with aerosolized cyclosporine delivery. J Surg Res 1993 Jun;54(6):597-602 PMID: 8412070

Pubmed ID

8412070

Abstract

Cyclosporine immunosuppression remains vital for successful lung transplantation. Cyclosporine also functions as a membrane active biological response modifier and has been noted to have a variable effect on ischemia-reperfusion (I/R) injury in various tissues. Glutathione plays an important role in the endogenous antioxidant defense system; plasma oxidized glutathione (GSSG) levels are useful as a sensitive indicator of in vivo oxidant stress and I/R injury. Lung transplantation results in ischemia, followed by a period of reperfusion, potentially producing functional injury. This study was designed to evaluate the effect of cyclosporine on oxygen radical generation in a model of single-lung transplantation. Single-lung transplantation was performed in 12 mongrel puppies, with animals assigned to receive either intravenous or aerosolized cyclosporine. Arterial blood and bronchoalveolar lavage fluid (BALF) samples were obtained to determine GSSG levels via a spectrophotometric technique. Samples were obtained both prior to and following the revascularization of the transplanted lung. Whole blood and tissue cyclosporine levels were determined via an high-performance liquid chromatography technique 3 hr following the completion of the transplant. Aerosolized cyclosporine administration resulted in greatly decreased arterial plasma and BALF GSSG levels, whole blood cyclosporine levels, and equivalent tissue cyclosporine levels when compared to intravenous cyclosporine delivery. These findings support the hypothesis that the transplanted lung is a source of GSSG production and release into plasma. Additionally, these findings suggest that cyclosporine may have a direct antioxidant effect on pulmonary tissue, with this activity occurring at the epithelial surface, an area susceptible to oxidant injury.

Author List

Katz A, Coran AG, Oldham KT, Guice KS

Author

Keith T. Oldham MD Professor in the Surgery department at Medical College of Wisconsin




Scopus

2-s2.0-0027484051   4 Citations

MESH terms used to index this publication - Major topics in bold

Aerosols
Animals
Antioxidants
Bronchoalveolar Lavage Fluid
Cyclosporine
Dogs
Glutathione
Lung Transplantation
Oxidation-Reduction
jenkins-FCD Prod-321 98992d628744e349846c2f62ac68f241d7e1ea70