This PhD thesis is aimed to study the role of aldehydes in the pathogenesis of a number of diseases, elucidation of the mechanisms of their regulatory and toxic action in the body and the search for new means to reduce the pathological consequences of their hyperproduction.
By in vitro experiments it was shown that aldehydes (ribose, glyoxal, methylglyoxal, and formaldehyde) differ in the intensity of protein modifications formation, such as carbonylation of proteins, the formation of fluorescent adducts, the formation of intermolecular protein crosslinks. The defined scales of activity of these aldehydes on the investigated properties do not coincide. In particular, formaldehyde and methylglyoxal form a small amount of fluorescent adducts, but have the highest polymerization activity.
It has been shown that the potential acceptor of aldehydes N-acetyl-L-cysteine reduces the effect of carbonyl compounds on the development of oxidative/carbonyl stress under conditions of rhabdomyolysis induced by glycerol. The observed effects may be related to the ability of N-acetyl-L-cysteine (cystine, cysteine) metabolic products to form covalent complexes with aldehydes.
Using type I diabetes mellitus model in rats, it was demonstrated that the use of "Complex dietary supplement in hypercarbonyl state" led to a decrease in the intensity of hypercarbonyl state according to such indicators as decrease in the level of total aldehydes, aldehyde-modified proteins (CML), carbonyl groups in proteins, low molecular weight thiol-containing compounds.
It was established that long-term administration of semicarbazide (aldehyde acceptor) to rats led to a significant decrease in weight and ratio of mass coefficient of organs, changes in skeletal architecture and bone mineral composition and increased catabolism of purines as well as prooxidant processes, decrease in the activity of semicarbazide-sensitive amino oxidase, superoxide dismutase and lysyl oxidase, concentration of aldehydes and increase in the activity of glutathione-dependent formaldehyde dehydrogenase and alkaline phosphatase.
Using Lewis lung carcinoma model, it was demonstrated that the administration of modified creatine (with a semicarbazide concentration of 0.00024%) resulted in reduced oxidative/carbonyl stress in the lung of mice by inhibiting the activity of a key enzyme modifying the structural and functional state of extracellular matrix, lysyl oxidase, as well as enzymes of oxidative deamination of biogenic amines and polyamines (diamine oxidase and polyamine oxidase), and, as a consequence, suppression of the tumor process.
The results obtained indicate that aldehydes are an important biochemical factors in the development of pathologies accompanied by carbonyl stress both with a decrease in their concentration (lathyrism) and with an increase (diabetes, rhabdomyolysis, Lewis lung carcinoma). The use of these experimental animal models has demonstrated the efficiency of complex dietary supplements developed by us to reduce the effects of carbonyl and oxidative stress as well as to improve the course of simulated pathological conditions.
