concanavalin-a and mitoquinone

Despite knowledge regarding the effects of antioxidants in ameliorating oxidative damage, evidence concerning their effects on activated immune cells is lacking. Here, a concanavalin A (Con A)-induced hepatitis mouse model was used to investigate the protective effects and immune regulatory mechanisms of mitochondrial-targeted ubiquinone (MitoQ).. NKT cells were critical for extensive pro-inflammatory cytokine production and prolonged liver injury upon Con A challenge, while IFN-γ-producing non-NKT cells played an important role during the hyperacute phase. MitoQ treatment not only ameliorated NKT cell-independent hyperacute hepatitis within 12 h post Con A administration but also alleviated NKT cell-dependent extended liver injury at 24 h. The underlying mechanisms involved an inhibition of the heightened activation of iNKT cells and conventional T cells, suppression of the excessive production of IFN-γ, TNF-α and IL-6, and modulation of aberrant AMPK and mTORC1 pathways.. MitoQ efficiently alleviates Con A-induced hepatitis through immune regulation, suggesting a new therapeutic approach for immune-mediated liver injury by targeting mitochondrial ROS.

Topics: AMP-Activated Protein Kinases; Animals; Antigens, CD1d; Antioxidants; Concanavalin A; Cytokines; Female; Hepatitis; Immunomodulation; Liver; Male; Mechanistic Target of Rapamycin Complex 1; Mice, Inbred C57BL; Mice, Knockout; Mitochondria; Natural Killer T-Cells; Organophosphorus Compounds; Reactive Oxygen Species; Ubiquinone