Abstract

Huntington’s disease (HD) is a progressive neurodegenerative disorder that is characterized by abnormal aggregation of mutant huntingtin proteins.  n neurons, they can initiate toxic effects, followed by a cascade of pathogenic mechanisms associated with bioenergetic defects, subsequent excitotoxicity, mitochondrial dysfunction, oxidative stress, transcriptional alterations, and apoptosis.

The influence of 3-oxy-6-methyl-2-ethylpyridine succinate (OMEPS) (50 mg/kg intraperitoneally (i.p.) once per day for two weeks) on prooxidant/antioxidant homeostasis of brain mitochondria of rats with modeled Huntington’s disease were studied. Mitochondrial toxin 3-nitro propionic acid (3-NPA), which selectively inhibits complex II of the electron transport chain (ETC)(1), was administered at a dose of 10 mg/kg i.p. once per day for two weeks to induce HD-like symptoms.

It was registered that the use of OMEPS against the background of 3-NPA intoxication weakened the intensity of oxidative processes in brain mitochondria: the content of secondary products of lipid peroxidation, hydrogen peroxide, and GSSG decreased, and the ratio of GSH/GSSG, the activity of ETC including succinate dehydrogenase increased.  values of GSH content, activity, and expression of Mn-SOD proteins, as well as glutathione-dependent and NADPH+-generating enzymes, were increased in comparison with similar indicators in animals with 3-NPA intoxication. the influences of succinic acid derivatives on protein expression of pro- and anti-apoptotic markers such as p53, and Bcl2 were demonstrated as well.  hus, OMEPS reduced brain mitochondrial damage caused by 3-NPA due to the increasing of protective proteins effects of endogenous antioxidant protection against the background of weakening of both oxidative processes and apoptosis.