Aspirin-triggered resolvin D1 alleviates paraquat-induced acute lung injury in mice

Abstract

AimsIn the present study, we aimed to evaluate the role of aspirin-triggered resolvin D1 (AT-RvD1) in paraquat (PQ)-induced acute lung injury (ALI) in mice. Main methodsWe used C57BL/6J mice as experimental subjects to establish mouse models of ALI via intraperitoneal (IP) injection of PQ (28 mg/kg). The mice were then administered AT-RvD1 (10 or 100 ng) via the tail vein 2 h after exposure to PQ and were sacrificed at 72 h post exposure to harvest bronchoalveolar lavage fluid (BALF), blood and lung tissue samples. The samples were used to evaluate the histopathological changes, inflammation reaction and oxidative stress in the lung tissues. Key findingsCompared with those of the PQ group, the administration of AT-RvD1 significantly (1) alleviated the histopathological changes in the lung tissues; (2) reduced the lung W/D weight ratio and the total protein content in the BALF; (3) activated nuclear factor erythroid-2 related factor 2 (Nrf2) and up-regulated the expression of its downstream genes (NADPH: quinone oxidoreductase-1, NQO1 and heme oxygenase-1, HO-1); (4) reduced the malondialdehyde(MDA) level in the lung tissues; (5) reduced the total cell, neutrophil, and macrophage counts in the BALF; (6) reduced the myeloperoxidase (MPO) activity in the lung tissues; (7) reduced the percent of Ly-6G+ CD41+ cells in the peripheral blood; (8) inhibited the activation of nuclear factor-κB (NF-κB) and the expression of P-selectin; and (9) reduced interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) levels in the BALF. SignificanceAdministration of AT-RvD1 can effectively inhibit PQ-induced oxidative stress injury, inflammatory responses, and pulmonary edema, thereby alleviating PQ-induced ALI.