Hyperhomocysteinemia is a risk factor for many human diseases, including pulmonary pathologies. In this context much interest attracts secondary mitochondrial dysfunction, which is an important link in pathogenesis of diseases associated with hyperhomocysteinemia. The study was conducted using male Wistar rats. It was found that under conditions of severe hyperhomocysteinemia caused by administration of methionine, homocysteine was accumulated in lung mitochondria thus suggesting a direct toxic effect on these organelles. However, we have not observed any significant changes in the activity of mitochondrial enzymes involved in tissue respiration (succinate dehydrogenase) and oxidative phosphorylation (H+-ATPase) and of cytoplasmic lactate dehydrogenase. Also there was no accumulation of lactic acid in the cytoplasm. Animals with severe hyperhomocysteinemia had higher levels of lung mitochondrial protein carbonylation, decreased reserve-adaptive capacity, and increased superoxide dismutase activity. These results indicate that severe hyperhomocysteinemia causes development of oxidative stress in lung mitochondria, which is compensated by activation of antioxidant protection. These changes were accompanied by a decrease in the concentration of mitochondrial nitric oxide metabolites. Introduction to animals a nonselective NO-synthase inhibitor L-NAME caused similar enhancement of mitochondrial protein carbonylation. It demonstrates importance of reducing bioavailability of nitric oxide, which is an antioxidant in physiological concentrations, in the development of oxidative stress in lung mitochondria during hyperhomocysteinemia. Key words: hyperhomocysteinemia, nitric oxide, lung, oxidative stress, mitochondria
Medvedev D.V., Zvyagina V.I., Uryasev O.M., Belskikh E.S., Bulatetskiy S.V., Ryabkov A.N. (2017) Metabolic changes in pulmonary mitochondria of rats with experimental hyperhomocysteinemia. Biomeditsinskaya Khimiya, 63(3), 248-254.
Medvedev D.V. et al. Metabolic changes in pulmonary mitochondria of rats with experimental hyperhomocysteinemia // Biomeditsinskaya Khimiya. - 2017. - V. 63. -N 3. - P. 248-254.
Medvedev D.V. et al., "Metabolic changes in pulmonary mitochondria of rats with experimental hyperhomocysteinemia." Biomeditsinskaya Khimiya 63.3 (2017): 248-254.
Medvedev, D. V., Zvyagina, V. I., Uryasev, O. M., Belskikh, E. S., Bulatetskiy, S. V., Ryabkov, A. N. (2017). Metabolic changes in pulmonary mitochondria of rats with experimental hyperhomocysteinemia. Biomeditsinskaya Khimiya, 63(3), 248-254.
Gulsen M., Yesilova Z., Bagci S., Uygun A., Ozcan A., Ercin C.N., Erdil A., Sanisoglu S.Y., Cakir E., Ates Y., Erbil M.K., Karaeren N., Dagalp K. (2005) J. Gastroenterol. Hepatol, 20, 1448-1455. CrossRef Scholar google search
Seemungal T.A., Lun J.C., Davis G., Neblett C., Chinyepi N., Dookhan C., Drakes S., Mandeville E., Nana F., Setlhake S., King C.P., Pinto Pereira L., Delisle J., Wilkinson T.M., Wedzicha J.A. (2007) Int. J. COPD, 2, 313-321. CrossRef Scholar google search