Coenzyme Q10 attenuates lung and liver fibrosis via modulation of autophagy in methotrexate treated rat

The present study was conducted to investigate the potential protective effects of coenzyme Q 10 (CoQ10) administration on methotrexate induced lung and liver fibrosis in rat model, and to explore our hypothesis regarding its possible mechanism of action through reactivation of autophagy pathway. Methotrexate induced fibrosis was achieved by intraperitoneal injections twice a week for 4 weeks. A combined treatment of CoQ10 and methotrexate were used. Blood samples for biochemical analysis, lung and livers tissue for biochemical and histopathological analysis, were investigated. Concomitant treatment of CoQ10 & methotrexate caused improvement in histological picture of the lung and liver tissues, liver function and oxidative stress biomarkers, modulation of autophagy genes [mammalian target of rapamycin (m-TOR), Microtubule-associated proteins 1 A/1B light chain 3 (MAP1LC3B), and Sequestosome 1 ubiquitin-binding protein p62 (p62/SQSTM1)] with simultaneous reduction in High Mobility Group Protein B1 (HMGB1). Based on our results we postulated that CoQ10 up regulates autophagy pathway that could explain its protective properties against lung and liver fibrosis caused by methotrexate treatment in current study rat model.