The aim: To investigate the effect of water-soluble form of quercetin on the indices reflecting the progression of oxidative-nitrosative stress in the cerebral tissues and the periodontium of rats after experimental TBI. Materials and methods: The studies were conducted on 30 white rats of the Wistar line weighing 180-220 g, divided into 3 groups: the 1st group included pseudo-injured animals (subjected to ether anaesthesia, fixation without TBI modeling), the 2nd group included the animals exposed to modeled moderate TBI, the 3rd group involved the rats, which were given injections with water-soluble form of quercetin (corvitin, “Borshchahivskiy CPP”, Ukraine) intraperitoneally in a daily dose of 10 mg/kg recalculated for quercetin for 7 days following the TBI modeling. The formation of superoxide radical anion (.О2 -), activity of NO-synthase – total (NOS), its constitutive and inducible isoforms (cNOS, iNOS) – and concentration of peroxynitrite were evaluated spectrophotometrically. The level of lipid peroxidation (LPO) in the tissues was evaluated by the formationof a stained trimethine complex during the reaction of tiobarbituric acid (TBA). The activity of the antioxidant system was assessed by increasing in the concentration of TBA active products during 1.5 hour incubation in iron-ascorbate buffer solution, as well as by the activity of antioxidant enzymes – superoxide dismutase (SOD) and catalase. Results: The use of quercetin under the experimental conditions significantly reduced the О2 - generation by NADPH- and NADH-dependent electron transport chains by 30.2 and 35.0% (in the cerebral hemispheres) and by 23.5 and 32.5% (in the soft periodontal tissues), respectively, compared to the findings in the 2nd group. The production of this radical by leukocyte NADPH oxidase in these organs was inferior to the value of the 2nd group by 39.3 and 29.9%. We revealed that the use of quercetin in the experimental conditions probably reduced the activity of NOS, including iNOS, by 38.2 and 45.3% (in the cerebral hemispheres) and by 53.5 and 66.9% (in the soft periodontal tissues), respectively, compared with the findings in the 2nd group. Under these conditions, the cNOS activity went up by 50.0% and doubled, the peroxynitrite content was lower by 19.5 and 32.1% than that in the 2nd group. The administration of quercetin in the experimental conditions significantly reduced the concentration of TBA-active products in the homogenate of cerebral hemispheres and soft periodontal tissues. The development of decompensated LPO is also confirmed by a decrease in the activity of SOD and catalase. Conclusions: on the 7th day after modeling moderate TBI in rats the signs of oxidative-nitrosative stress are found not only in locus morbi (in the tissue of the cerebral hemisphere), but also in distant organs (periodontal tissues). Applying of water-soluble form of quercetin significantly reduces signs of oxidative-nitrosative stress in the tissue of the cerebral hemisphere of rats, as well as in periodontal tissues on the 7th day after moderate TBI modeling.
The study was aimed as investigating the effects of inhibitors of transcription factors NF kappa B and AP-1 activation on the development of oxidative-nitrosative stress in rat cerebral hemispheres following experimental traumatic brain injury (TBI). The study included 60 white Wistar male rats weighing 180-220 g, divided into 4 groups of 7 animals in each: the 1st group included pseudo-injured animals subjected to the same manipulations (ether anaesthesia, fixation) as the animals in the experimental groups, except for TBI modelling, the 2nd group included the animals exposed to modelled TBI, the 3rd and 4th groups involved the rats who received ammonium pyrolidine dithiocarbamate, the nuclear translocation inhibitor NF kappa B in a dose of 76 mg/kg and the inhibitor AP-1 SR 11302 in a dose of 1 mg/kg, respectively for 7 days following the TBI modelling. On the 7th day after the simulation of a moderate TBI in rat cerebral hemisphere tissue, the following signs of oxidative-nitrosative stress have been detected: increased production of superoxide radical anion by NADPH and NADH-dependent electron transport chains, increased activity of nitric oxide synthase (total and inducible), a decrease and impairment of the coupling of its constitutive isoform, growth in the concentration of peroxynitrite, the development of decompensated lipid peroxidation. The application of transcription factor inhibitors NF kappa B (PDTC) and AP-1 (SR 11302) significantly reduces the signs of oxidative-nitrosative stress in the tissue of rat cerebral hemispheres on the 7th day of the experiment, reduces the production of superoxide anion radical and the activity of nitric oxide synthase (total and inducible), improves the coupling of its constitutive isoform, limits the peroxynitrite concentration, and enhances the antioxidant potential.
This study aimed at investigating the effect of modulators of transcription factors NF-κB, AP-1 and Nrf2 on the behavioural responses of rats in the "Dark-light chamber" and "Open field" tests following the simulation of traumatic brain injury (TBI). The study included 42 white Wistar male rats weighing 180-220 g, divided into 6 groups of 7 rats in each: the control group included the animals exposed to the above mentioned tests before TBI modelling and 3 – 7 days after it; as for the animals of other groups, for 7 days after TBI simulation they were given intraperitoneal injections of the following transcription factor modulators: ammonium pyrrolidine dithiocarbamate, an inhibitor of nuclear translocation NF-κB, was injected in a dose of 76 mg/kg; AP-1 SR 11302 inhibitor given in a dose of 1 mg/kg; Nrf2 inductors as dimethyl fumarate given in a dose of 15 mg/kg of a 10% dimethyl sulfoxide solution and epigallocatechin-3-gallate in a dose of 1 mg/kg as well as a water-soluble form of quercetin (corvitin), which acts as an NF-κB inhibitor and Nr inducer, in a dose of 100 mg / kg (10 mg / kg in terms of quercetin). Unlike the test animals, the rats of the control group were given intraperitoneal injections of 1 ml of isotonic sodium chloride solution. It has been found out that during the first week following TBI simulation, the locomotor activity and psycho-emotional state of the rats were disturbed: the indicators of motor and exploratory activity, orienting reaction became deteriorated, anxiety and fear increased as well as the frequency of self-grooming actions. The use of inhibitors of transcription factors NF-κB (ammonium pyrolidindithiocarbamate) and AP-1 (SR 11302), Nrf2 inducers (dimethyl fumarate and epigallocatechin-3-gallate) and the water-soluble form of quercetin (corvitin) for the 1st week after TBI simulation improves motor performance and exploratory activity, orienting reaction, and reduces emotional anxiety and fear as well.