Metabolic changes in pulmonary mitochondria of rats with experimental hyperhomocysteinemia

Abstract

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.

Features of microscopic changes in lung structure of young rats under conditions of hyperhomocysteinemia

“…It has been established that in severe hyperhomocysteinemia, HC accumulates in the mitochondria of the lungs in rats, causing a direct toxic effect on them. Under these conditions, the metabolism of NO is impaired and its bioavailability is reduced, however, the production of reactive oxygen species is enhanced against the background of inhibition of the reserve-adaptive potential of lung mitochondria and, as a consequence, damage to the organ parenchyma [12].…”

Features of histological changes in the lungs of mature animals under conditions of hyperhomocysteinemia

“…Significant accumulation of homocysteine in the organelle leads to the development of oxidative stress due to nitric oxide deficiency and oxidative modification of proteins. Mitochondrial dysfunction causes cell apoptosis and lung tissue damage [14].…”