QUERCETIN LIMITS THE PROGRESSION OF OXIDATIVE AND NITROSATIVE STRESS IN THE RATS’ TISSUES AFTER EXPERIMENTAL TRAUMATIC BRAIN INJURY

Abstract

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 formation of 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.