Endogeous sulfur dioxide protects against oleic acid-induced acute lung injury in association with inhibition of oxidative stress in rats

Abstract

The role of endogenous sulfur dioxide (SO₂), an efficient gasotransmitter maintaining homeostasis, in the development of acute lung injury (ALI) remains unidentified. We aimed to investigate the role of endogenous SO₂ in the pathogenesis of ALI. An oleic acid (OA)-induced ALI rat model was established. Endogenous SO₂ levels, lung injury, oxidative stress markers and apoptosis were examined. OA-induced ALI rats showed a markedly downregulated endogenous SO₂/aspartate aminotransferase 1 (AAT1)/AAT2 pathway and severe lung injury. Chemical colorimetry assays demonstrated upregulated reactive oxygen species generation and downregulated antioxidant capacity in OA-induced ALI rats. However, SO₂ increased endogenous SO₂ levels, protected against oxidative stress and alleviated ALI. Moreover, compared with OA-treated cells, in human alveolar epithelial cells SO₂ downregulated O₂⁻ and OH⁻ generation. In contrast, L-aspartic acid-β-hydroxamate (HDX, Sigma-Aldrich Corporation), an inhibitor of endogenous SO₂ generating enzyme, promoted free radical generation, upregulated poly (ADP-ribose) polymerase expression, activated caspase-3, as well as promoted cell apoptosis. Importantly, apoptosis could be inhibited by the free radical scavengers glutathione (GSH) and N-acetyl-L-cysteine (NAC). The results suggest that SO₂/AAT1/AAT2 pathway might protect against the development of OA-induced ALI by inhibiting oxidative stress.