ISSN 2415-3060 (print), ISSN 2522-4972 (online)
  • 14 of 67
УЖМБС 2020, 5(4): 117–123
Experimental Medicine and Morphology

Influence of Nrf2 Transcription Factor Inducers on the Development of Oxidative-Nitrosative Stress in the Tissue of Cerebral Hemispheres in Rats after Modeled Traumatic Brain Injury

Yavtushenko I. V., Kostenko V. O.

The purpose of the study was to investigate the effects produced by inducers of the Nrf2 - antioxidant-responsive element (ARE) signaling system on the indices of oxidative-nitrosative stress development in cerebral hemispheres of rats following experimental traumatic brain injury. Material and methods. The study included 28 Wistar white male rats weighing 180-220 g, divided into 4 groups of 7 animals each: the 1st group included pseudo-injured animals subjected to the same manipulations (ether anesthesia, fixation) as the animals in the experimental groups, except for traumatic brain injury modeling; the 2nd group included the animals exposed to modeled traumatic brain injury, the 3rd and 4th groups involved the rats who received Nrf2-ARE system inductors intraperitoneally: dimethyl fumarate (DMF) in 10% dimethyl sulfoxide solution in a dose of 15 mg/kg and epigallocatechin-3-gallate (EGCG) in a dose of 1 mg/kg, for 7 days following the traumatic brain injury modeling. Results and discussion. Analysis of cerebral tissue homogenates demonstrated that, when applying DMF, the production of superoxide anion radical (.О ) by NADPH and NADH-dependent electron transport chains and leukocyte NADPH-oxidase significantly decreases; the activity of NO synthase (NOS, total and its inducible isoforms) reduces, peroxynitrite content, concentration of secondary products of lipid peroxidation (TBA-active compounds) and their increase during incubation in a pro-oxidant iron-ascorbate buffer solution go down compared to the findings in the 2nd group. At the same time, the activity of the NOS constitutive isoform and NOS coupling index, as well as the activity of superoxide dismutase and catalase increase. The administration of EGCG following the traumatic brain injury modeling resulted in the decrease in production of .О by NADPH and NADH dependent electron transport chains and by leukocyte NADPH oxidase, NOS activity (total, inducible and constitutive isoforms), peroxynitrite content, concentration of TBA-active compounds and their increase during incubation in pro-oxidant buffer solution with growing activity of superoxide dismutase and catalase. Conclusion. The study showed that the use of electrophilic inductors of the Nrf2 - ARE system (DMF and EGCG) significantly alleviated the signs of oxidative-nitrosative stress in the cerebral tissue of rats on the 7th day after the modeling of moderate traumatic brain injury: it reduced the production of reactive oxygen and nitrogen species, reduced peroxide lipid oxidation, and increased antioxidant potential.

Keywords: transcription factor Nrf2, dimethyl fumarate, epigallocatechin-3-gallate, traumatic brain injury, oxidative-nitrosative stress, brain

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