OXIDATIVE MECHANISMS UNDERLYING BRAIN CELL DAMAGE IN RATS UNDER CHANGES IN DURATION OF THE LIGHTDARK CYCLES

Abstract

One of the main mechanisms underlying cell damage is lipid peroxidation, which is characterized by increased levels of free radical, products of lipid peroxidation chain reactions, and alterations in the activity of the antioxidant system in tissues. Therefore, the objective of this study is to investigate the proand antioxidant balance in rat brain homogenate under conditions of disrupted "light-dark" cycles. The study involved 28 white Wistar rats weighing 150-200 gm, divided into two groups: control (15) and the group of animals exposed to acute desynchronosis simulation (13). To simulate desynchronosis, a normal "light-dark" cycle of 12 hours of light and 12 hours of darkness was initially established for three weeks, followed by a shift of the "light-dark" phases backward by six hours over the next three days. The animals were kept in standard conditions with a balanced diet in the vivarium, and the study adhered to the principles of biomedical ethics.
 The results obtained indicate a significant increase in the activity of superoxide anion radical production in the brain tissues of the rats with modelled desynchronosis by 75.8% compared to the control group. This increase is attributed to the NADPH-oxidase mechanism by 20.2% and to xanthine oxidase mechanisms by 28%. The concentration of TBA-active products increased by 36.8%, the growth of TBA-active products elevated by 30%, and the activity of the key antioxidant enzymes, superoxide dismutase and catalase, decreased by 53% and 14%, respectively, in the second group of animals. Furthermore, in the brain tissues of rats with disrupted "light-dark" cycles, there were found elevated levels of nitrites by 23.8%, nitrosothiols by 19%, and peroxynitrites by 69%, along with a reduction in the activity of total NO-synthase by 59.1%, inducible NO-synthase by 61.1%, and constitutive NO-synthase by 9% compared to the control group. The activity of ornithine decarboxylase increased by 26.5% in the brain tissues of the rats with simulated desynchronosis compared to the control group.
 In conclusion, the disruption of "light-dark" cycles leads to the development of oxidative stress in brain tissues of animals and is characterized by increased production of reactive oxygen species and diminished antioxidant protection. Acute desynchronosis decreases nitric oxide production through the NO-synthase pathway, while increasing the accumulation of toxic nitric oxide metabolites in the brain tissues of rats, thereby posing a potential risk of nitrosative stress. Furthermore, alterations in the normal light regimen of the day activate the arginase pathway of L-arginine metabolism and result in increased glutamate production in the brain tissues of rats, potentially leading to oxidative stress.