The glutathione system and S-glutathionilation of proteins in the brain structures of rats with aluminum neurotoxicosis and the application of coenzyme A biosynthesis modulators
The introduction considers literature data on the mechanisms of action of aluminum chloride when used to model neurodegenerative diseases in animals, namely, the prooxidant effect of this compound and the initiation of oxidative stress development, as well as modulation of the functions of mitochondria and signaling pathways of metabolism in the brain. Information on the role of disorders of the glutathione system in the development of brain tissue damage in aluminum neurotoxicosis and its participation in the process of S-glutathionylation of proteins is provided. In the main part, an experimental model of aluminum neurotoxicosis in rats is described and a scheme for the introduction of coenzyme A biosynthesis modulators (D-panthenol, D-pantetin and calcium homopantothenate) is given. The used methods are used to assess the severity of oxidative stress, analyze the content of total and oxidized glutathione by the recycle enzymatic method, determine the activity of key glutathione metabolism and biosynthesis enzymes, determine the content of S-glutathionylated proteins, as well as the content of protein thiols and disulfides in brain structures. It was found that chronic administration of aluminum chloride leads to a significant increase in the content of lipid peroxidation products, a significant decrease in the ratio of reduced to oxidized form of glutathione in the cerebral hemispheres, basal ganglia and hippocampus of rat brain. In this case, the activity of the enzymes of the redox transformations of glutathione changes and the activity of the enzymes of its biosynthesis is reliably inhibited. A noticeable activation of S-glutathionylation of proteins in brain structures was found. At the same time, the content of protein thiols and disulfides changes to a lesser extent. It has been shown that the precursors of CoA biosynthesis help to reduce the effects of oxidative stress, changes in the redox potential of the glutathione system, and S-glutathionylation of proteins caused to the action of aluminum chloride.