Protective effects of endothelin-A receptor antagonist BQ123 against LPS-induced oxidative stress in lungs

The aim of this study was to assess whether endothelin-a receptor (eta-r) blocker,bq123,influences lung edema,lipid peroxidation (tbars),hydrogen peroxide (h2o2),tnf-α concentration or the glutathione redox system in the lung homogenates obtained from lps-induced endotoxic shock rats. the study was performed on male wistar rats (n = 6 per group) divided into groups: (1) saline,(2) lps (15 mg/kg)-saline,(3) bq123 (0.5 mg/kg)-lps,(4) bq123 (1 mg/kg)-lps. the eta-r antagonist was injected intravenously 30 min before lps administration. five hours after saline or lps administration,animals were sacrificed and lungs were isolated for indices of lung edema,oxidative stress and tnf-α concentration. injection of lps alone resulted in lung edema development and a marked increase in tnf-α (p < 0.02),tbars (p < 0.02),and h2o2 (p < 0.01) concentrations as well as a depletion of total glutathione (p < 0.01). administration of bq123 (1 mg/kg),before lps challenge,led to a significant reduction in tnf-α and h2o2 concentrations (p < 0.05) and elevation of both total glutathione and the gsh/gssg ratio (p < 0.05). however,it did not prevent lps-induced tbars increase and lung edema formation. interestingly,a lower dose of bq123 was much more effective in decreasing h2o2,tbars,as well as tnf-α levels (p < 0.02,p < 0.05,p < 0.05,respectively). that dose was also effective in prevention of lung edema development (p < 0.01). taken together,the obtained results indicate that bq123 is highly effective in decreasing lps-induced oxidative stress in lungs. moreover,the dose of 0.5 mg/kg of the antagonist showed to be more effective in decreasing free radical generation and lung edema in endotoxemic rats. copyright © 2011 by institute of pharmacology polish academy of sciences.