Comparison of four pharmacological strategies aimed to prevent the lung inflammation and paraquat-induced alveolar damage

Abstract

Objective : The aim of this study was to compare in vivo effect of five pharmacological options on inflammation and pulmonary fibrosis induced by paraquat. Methods: 54 Wistar SPF rats were used. After 2 hours post-intoxication with paraquat ion, groups of 9 animals were randomly assigned to : (1) cyclophosphamide plus dexamethasone (2) low molecular weight heparin (3) unfractionated heparin (4) vitamin C every 24 h , (v) atorvastatin or (vi) placebo with intraperitoneal saline .Lung inflammation, alveolar injury, hepatocyte damage, hepatic regeneration, acute tubular necrosis and kidney congestion were evaluated. Results: In the control group 100% of animals presented moderate and severe lung inflammation, while in the groups with atorvastatin and intratracheal heparin this proportion was lower (55.5% ; CI 26.6 – 81.3%) (p = 0.025). A lower degree of moderate or severe hepatic regeneration was evident in the treatment groups with atorvastatin (p = 0.009). In this study was demonstrated that statins and heparin may have a protective effect in the paraquat-induced destructive phase. More evidence are needed to evaluated of dose response effects of these drugs before to study in clinical trials.