Metformin prevents ischemia reperfusion-induced oxidative stress in the fatty liver by attenuation of reactive oxygen species formation

0448388 - FGÚ 2016 RIV US eng J - Článek v odborném periodiku
Cahová, M. - Páleníčková, E. - Danková, H. - Sticová, E. - Burian, M. - Drahota, Zdeněk - Červinková, Z. - Kučera, O. - Gladkova, Ch. - Stopka, Pavel - Křížová, Jana - Papáčková, Z. - Oliyarnyk, O. - Kazdová, L.
Metformin prevents ischemia reperfusion-induced oxidative stress in the fatty liver by attenuation of reactive oxygen species formation.
American Journal of Physiology-Gastrointestinal and Liver Physiology. Roč. 309, č. 2 (2015), G100-G111. ISSN 0193-1857. E-ISSN 1522-1547
Grant CEP: GA MŠMT(CZ) LL1204
Institucionální podpora: RVO:67985823 ; RVO:61388980
Klíčová slova: metformin * oxidative stress * mitochondrial respiration * liver injury * 31P MR spectroscopy
Kód oboru RIV: EB - Genetika a molekulární biologie; CA - Anorganická chemie (UACH-T)
Impakt faktor: 3.297, rok: 2015

Nonalcoholic fatty liver disease is associated with chronic oxidative stress. In our study, we explored the antioxidant effect of antidiabetic metformin on chronic [high-fat diet (HFD)-induced] and acute oxidative stress induced by short-term warm partial ischemia-reperfusion (I/R) or on a combination of both in the liver. Metformin treatment prevented acute stress-induced necroinflammatory reaction, reduced alanine aminotransferase and aspartate aminotransferase serum activity, and diminished lipoperoxidation. The effect was more pronounced in the HFD than in the SD group. The metformin-treated groups exhibited less severe mitochondrial damage and apoptosis. Metformin-treated HFD-fed rats subjected to I/R exhibited increased antioxidant enzyme activity as well as attenuated mitochondrial respiratory capacity and ATP resynthesis. The exposure to I/R significantly increased NADH- and succinate-related mitochondrial ROS production in vitro. The effect of I/R was significantly alleviated by previous metformin treatment. Metformin downregulated the I/R-induced expression of proinflammatory and infiltrating monocyte and macrophage markers. Our data indicate that metformin reduces mitochondrial performance but concomitantly protects the liver from I/R-induced injury. We propose that the beneficial effect of metformin action is based on a combination of three contributory mechanisms: increased antioxidant enzyme activity, lower mitochondrial ROS production, and reduction of postischemic inflammation
Trvalý link: http://hdl.handle.net/11104/0250102