Effects of mitochondria-targeted antioxidant SS-31 on cigarette smoke-induced airway inflammation and oxidative stress in a mouse model

This study investigated whether mitochondria-targeted peptide SS-31 played a protective role in cigarette smoke (CS)-induced airway inflammation and oxidative stress in mice. Mice were exposed to CS for 4 weeks to establish a CS-induced airway inflammation model, then treated with SS-31. Pathological changes and oxidative stress in lung tissue, inflammatory cell counts and pro-inflammatory cytokines in bronchoalveolar lavage fluid (BALF) were examined. RNA sequencing from lung tissue and western blotting were conducted to investigate mechanisms. SS-31 attenuated CS-induced inflammatory injury of the airway. Numbers of total cells, neutrophils, and macrophages and levels of tumor necrosis factor α, interleukin 6, and matrix metallopeptidase 9 in BALF were markedly reduced by SS-31. SS-31 attenuated CS-induced oxidative stress by decresing malondialdehyde and myeloperoxidase levels, and increasing superoxide dismutase activity. It also reversed the expression of mitochondrial fission protein and optic atrophy 1 protein, and reduced cytochrome c release into the cytosol. RNA sequencing revealed that SS-31 changed CS-induced expression profiles and enriched MAPK pathway, western blotting confirmed that SS-31 inhibited the CS-activated MAPK pathway. SS-31 alleviates CS-induced airway inflammation and oxidative stress, possibly via the regulation of mitochondrial function and MAKP pathway, SS-31 may be a novel drug for CS-induced airway disorders. RNA-seq of CS vs SS-31H_CS in C57BL/6J mice