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(Chest. 2002;121:589-596.)
© 2002 American College of Chest Physicians

Changes in (Na + K)-Adenosine Triphosphatase Activity and Ultrastructure of Lung and Kidney Associated With Oxidative Stress Induced by Acute Ethanol Intoxication*

Ramón Rodrigo, MSc; Sergio Trujillo, MD; Cleofina Bosco, MSc; Myriam Orellana, MSc; Lilian Thielemann and Julia Araya

* From the Instituto de Ciencias Biomédicas, Programa de Farmacología Molecular y Clínica (Mr. Rodrigo, Dr. Trujillo, and Ms. Orellana), Programa de Morfología (Ms. Bosco), Programa de Patología (Ms. Thielemann), and Departamento de Nutrición (Ms. Araya), Facultad de Medicina, Universidad de Chile, Santiago, Chile.

Correspondence to: Ramón Rodrigo, MSc, Laboratorio de Fisiopatología Renal, ICBM, Programa de Farmacología Molecular y Clínica, Facultad de Medicina, Universidad de Chile, Independencia 1027, Casilla 70058, Santiago 7, Chile;

Study and objectives: (Na + K)-adenosine triphosphatase (ATPase) activity, oxidative stress parameters, and morphologic characteristics of the lung and kidney of rats under acute ethanol intoxication were assessed to investigate the pathogenic mechanism of tissue damage.

Design and interventions: Adult rats were given ethanol (5.5 g/kg) 3 h before performing the biochemical and morphologic studies. Oxidative stress was assessed by measuring the levels of reduced glutathione (GSH) and glutathione disulfide (GSSG), the activities of key antioxidant enzymes (ie, catalase [CAT], superoxide dismutase [SOD], and glutathione peroxidase [GSH-Px]) and malondialdehyde production. (Na + K)-ATPase, a membrane-bound enzyme, also was assayed.

Results: In the lung, ethanol increased MDA production by 60%, decreased GSH levels by 33%, decreased SOD and GSH-Px activity by 10%, and decreased (Na + K)-ATPase activity by 55%, whereas CAT activity was unaltered. Impaired surfactant secretion and cell adhesion of lung epithelial cells were found. In the kidney, ethanol did not influence the activity of (Na + K)-ATPase or lipid peroxidation, despite the reduction of both GSH and the GSH/GSSG ratio. Focally thickened glomerular basement membrane, apoptosis of foot processes, and tubulointerstitial fibrosis were found.

Conclusions: These data suggest that oxidative stress plays a role in mediating the ethanol-induced down-regulation of lung (Na + K)-ATPase. GSH depletion seems to be a major determinant of this effect. Independent mechanisms seem to account for the morphologic alterations of these organs.

Key Words: antioxidant enzymes • ethanol • glutathione • kidney • lung • (Na + K)-adenosine triphosphatase • malondialdehyde




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R. Rodrigo, S. Trujillo, and C. Bosco
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Experimental Biology and Medicine, September 1, 2006; 231(8): 1430 - 1438.
[Abstract] [Full Text] [PDF]




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