Metformin Attenuated Hyperoxia Induced Oxidative Damages on Different Tissues in Young Rats

Abstract

To the best of our knowledge, this is the first study investigating the protective effect of metformin against hyperoxia-induced oxidative and inflammatory damage to the liver, thymus, spleen, kidney and lung tissues of young rats. 40 Wistar albino separated to four equal groups such as: normoxia control group (NC), normoxia plus metformin group (NM, 25 mg/kg of metformin), hyperoxia (≥85% O2) group (HC), hyperoxia plus metformin group (HM, ≥85% O2; 25 mg/kg of metformin). To evaluate the antioxidant effect of metformin on rat tissues, we performed lipid peroxidation, protein oxidation , Na K ATPase activity and antioxidant capacity [ enzymatic: glutathione peroxidase (GP), glutathione reductase (GR), superoxide dismutase (SOD) and catalase (CAT) activity; non-enzymatic: glutathione (GSH) level] measurements. We also measured serum interleukin (IL)-1β, IL-6, IL-10 and tumor necrosis factor alfa (TNFα) cytokine levels and nuclear factor kappa B (NF-κB) activation to evaluate the anti-inflammatory effects of metformin. A statistically significant decrease was observed in the HM group in terms of tissue lipid peroxidation, protein oxidation, and DNA fragmentation measurements compared to the HC group, while enzymatic and non-enzymatic antioxidant capacity and Na K ATPase activity increased significantly. In the HM group, plasma IL-1β, IL-6, and TNF-α levels and NF-κB activation. decreased and IL-10 increased significantly compared to the HC group. In conclusion, metformin has a protective role against hyperoxia-induced oxidative and inflammatory damage in the liver, thymus, spleen, kidney and lung tissues of young rats.

Key words: hyperoxia, oxidative stress, inflammation,