Ramón Rodrigo, Sergio Trujillo, Cleofina Bosco, Myriam Orellana, Lilian Thielemann and Julia Araya Chest 2002;121;589-596 DOI 10.1378/chest.121.2.589
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Changes in (Na K)-Adenosine Triphosphatase Activity and Ultrastructure of Lung and Kidney Associated With Oxidative Stress Induced by Acute EthanolIntoxication*
Ramon Rodrigo, MSc; Sergio Trujillo, MD; Cleofina Bosco, MSc; ´ Myriam Orellana, MSc; Lilian Thielemann; and Julia Araya
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 tissuedamage. 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]) andmalondialdehyde 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 didnot 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 ethanolinduced down-regulation of lung (Na K)-ATPase. GSH depletionseems to be a major determinant of this effect. Independent mechanisms seem to account for the morphologic alterations of these organs. (CHEST 2002; 121:589 –596)
Key words: antioxidant enzymes; ethanol; glutathione; kidney; lung; (Na hyde K)-adenosine triphosphatase; malondialde-
Abbreviations: ATPase adenosine triphosphatase; CAT catalase; GSH glutathione; GSSG glutathione disulfide; GSH-Pxglutathione peroxidase; MDA malondialdehyde; ROS reactive oxygen species; SOD superoxide dismutase
generation of T hecrucial step in reactive oxygen species (ROS) is a the pathogenesis of tissue damage.1 The antioxidant defense system operates
*From the Instituto de Ciencias Biomedicas, Programa de ´ Farmacologıa Molecular y Clınica (Mr. Rodrigo, Dr. Trujillo, and ´ ´ Ms. Orellana), Programa deMorfologıa (Ms. Bosco), Programa ´ de Patologıa (Ms. Thielemann), and Departamento de Nutricion ´ ´ (Ms. Araya), Facultad de Medicina, Universidad de Chile, Santiago, Chile. This research was supported by grant 1990784 from the Fondo Nacional de Ciencia y Tecnologıa (FONDECYT). ´ Manuscript received January 10, 2001; revision accepted August 24, 2001. Correspondence to: Ramon Rodrigo, MSc,...