Protective effect of 5-amino salicylic acid against acute lung injury caused by paraquat poisoning / 医学研究生学报

ABSTRACT

ObjectiveThe mechanism of paraquat poisoning (PQP) inducing acute lung injury is not clear. Nuclear factor erythroid 2-related factor 2 (Nrf2 )-antioxidant response element (ARE) is found to be a most important endogenous antioxidant defense pathway. This study aimed to explore the protective effect of 5- amino salicylic acid (5-ASA) against PQP-induced acute lung injury by activating the Nrf2-ARE pathway.MethodsEighty healthy adult male SD rats were randomly divided into four groups blank control, 5-ASA control, PQP, and 5-ASA treatment. The animals in the PQP and 5-ASA treatment groups were injected with paraquat at 20 mg/kg into the left abdominal cavity for construction of the PQP model and those in the blank and 5-ASA control groups with isotonic saline at 1 mL. At 2 hours after modeling, the rats in the 5-ASA control and 5-ASA treatment groups received gavage of 5-ASA 75 at mg/kg for 3 successive days. At 1 and 3 days after observation, all the rats were sacrificed and the lower lobe of the right lung harvested for HE staining and observation of pathologic changes in the lung tissue. Meanwhile the left lung tissue was collected for determination of the expressions of Nrf2 and HO-1 proteins by Western blot.ResultsBehavioral changes were observed in the rats of the PQP and 5-ASA treatment groups, but less obvious in the latter. The alveolar wall capillaries of the rats in the PQP group were expanded and congested significantly, with widened alveolar septa and infiltration of a large number of inflammatory cells at 1 and 3 days, even severer at 3 days. The rats of the 5-ASA treatment group showed obviously reduced edema and the inflammatory cell infiltration at the corresponding time points as compared the PQP group. The lung tissue pathology scores were significantly higher in the 5-ASA treatment and PQP groups than in the blank control at 1 day (0.66±0.10 and 0.61±0.04 vs 0.18±0.05, P<0.05) and at 3 days (0.74±0.08 and 0.49±0.08 vs 0.16±0.02, P<0.05), but markedly lower in the 5-ASA treatment than in the PQP group (P<0.05). Both the expressions of Nrf2 and HO-1 proteins were remarkably higher in the 5-ASA control, PQP and 5-ASA treatment groups than in the blank control at 1 and 3 days (P<0.05), and so were they in the 5-ASA treatment than in the PQP group (P<0.05).Conclusion5-ASA can effectively reduce PQP-induced acute lung injury, which may be related to its up-regulation of the Nrf2 expression.