Transcriptional Regulation of Antioxidant Enzymes Activity and Modulation of Oxidative Stress by Melatonin in Rats Under Cerebral Ischemia / Reperfusion Conditions

• Published in: Neuroscience Vol. 406; pp. 653 - 666
• Main Authors: Kryl'skii, Evgenii D., Popova, Tatyana N., Safonova, Olga A., Stolyarova, Anna O., Razuvaev, Grigorii A., de Carvalho, Miguel Angelo Pinheiro
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 15-05-2019
• Subjects: Animals; antioxidant enzymes; Antioxidants - pharmacology; apoptosis; Brain - drug effects; Brain - metabolism; Brain Ischemia - drug therapy; Brain Ischemia - metabolism; Free Radicals - metabolism; Ischemia - drug therapy; Ischemia - metabolism; ischemia/reperfusion; Male; melatonin; Melatonin - metabolism; Melatonin - pharmacology; Nerve Tissue Proteins - metabolism; oxidative stress; Oxidative Stress - drug effects; Rats, Wistar; Reperfusion Injury - drug therapy; Reperfusion Injury - metabolism; Bcl-2; TRADD; apoptosis; LPO; antioxidant enzymes; FOXO1; ischemia/reperfusion; SOX2; CREB-ATF; HIF-1; NF-κB; S; MLT; Nrf2; Imax; FADD; GSH; Puma; GSSG; NBT; tgα2; TRAIL; AH; Bim; GP; SOD; BCL; IEG; GR; IL-1β; CIR; GT; SIRT1; POM; ARE; IKKß; TNF-α; PMS; Keap1; melatonin; oxidative stress; PCR; DC; Iκba
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2019.01.046

The article studies the effect of melatonin on the intensity of free radical oxidation, the functioning of the enzymatic components of the antioxidant system and their transcriptional regulation in rats with experimental cerebral ischemia/reperfusion of the brain. The development of ischemia/reperfusion was characterized by the activation of apoptotic processes and the accumulation of mRNA of the genes Sod1, Cat, Gpx1, Gsr, Hif-1α, Nrf2, Nfkb2, and Foxo1 in the rats' brains. The use of melatonin in the presence of the pathological induction led to a change in these parameters towards the control values. In addition, the introduction of the hormone was accompanied by a decrease in lactate content, the level of lipoperoxidation products and oxidative modification of proteins, indicators of biochemiluminescence in the brain and blood serum. At the same time, there was a shift in the activity of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase, which increased in the presence of a pathology, towards the control values. The revealed changes may be accounted for by antioxidant and neuroprotective properties of melatonin, which provided a decrease in the degree of mobilization of the protective systems in animal organism.
•Melatonin can affect the transcriptional regulation of antioxidant enzymes.•Melatonin contributes to the normalization of pro- and antioxidant processes.•Melatonin can modulate mobilization of the antioxidant system.