Apocynin prevents cigarette smoking‐induced loss of skeletal muscle mass and function in mice by preserving proteostatic signalling

• DOI: 10.1111/bph.15482
• Publication Date: 2021-04-05T05:44:52Z
• Authors: Stanley M. H. Chan; Ivan Bernardo; Chanelle Mastronardo; Kevin Mou; Simone N. De Luca; Huei Jiunn Seow; Aleksandar Dobric; Kurt Brassington; Stavros Selemidis; Steven Bozinovski; Ross Vlahos
• Keywords: Apocynin; Myostatin

Background and Purpose Skeletal muscle dysfunction is a major comorbidity of chronic obstructive pulmonary disease (COPD). This type may be direct consequence oxidative insults evoked by cigarette smoke (CS) exposure. The present study examined the effects potent Nox inhibitor reactive oxygen species (ROS) scavenger, apocynin, on CS‐induced dysfunction. Experimental Approach Male BALB/c mice were exposed to either room air (sham) or CS generated from nine cigarettes per day, 5 days week for 8 weeks, with without coadministration apocynin (5 mg·kg −1 , i.p.). C2C12 myotubes hydrogen peroxide (H 2 O ) water‐soluble extract (CSE) (500 nM) used as an experimental model in vitro. Key Results Eight weeks exposure caused mice, reflected 10% loss mass 54% strength tibialis anterior which prevented administration. In myotubes, H CSE myofibre wasting, accompanied ~50% muscle‐derived insulin‐like growth factor (IGF)‐1 two‐fold induction Cybb independent cellular inflammation. Expression myostatin MAFbx, negative regulators mass, up‐regulated under but not conditions. Apocynin treatment abolished CSE‐induced expression, preserving IGF‐1 expression signalling pathway downstream mammalian target rapamycin (mTOR), thereby preventing wasting. Conclusion Implications Targeted pharmacological inhibition Nox‐derived ROS alleviate lung systemic manifestations smokers COPD.