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

This study is aimed at investigating the effect of specific modulators of transcription factors NF-κB and Nrf2 on indicators of oxidative-nitrosative stress in periodontal soft tissues in the early post-traumatic period after experimental model of moderate traumatic brain injury (TBI). The experiment was conducted on 20 white male Wistar rats weighing 180-220 g, divided into 4 groups: the 1st (pseudo-traumatized animals, control 1) exposed to the same manipulations (ether anaesthesia, fixation) as in the experimental series, with the exception of TBI modelling; the 2nd group – after TBI modelling (control 2); animals of the 3rd and 4th groups following the TBI modelling received intraperitoneal injections of modulators of transcription factors for 7 days: the inhibitor of NF-κB nuclear translocation ammonium pyrrolidine dithiocarbamate in a dose of 76 mg/kg and the inducer of the transcription factor Nrf2 dimethyl fumarate in a dose of 15 mg/kg in 10 % dimethylsulfoxide solution, respectively. The study has shown that at the end of the early post-traumatic period (on the 7th day), the modelled TBI is accompanied by the development of oxidative-nitrosative stress in the soft tissues of the periodontium that is confirmed by an increase in the production of the superoxide anion radical by all its main sources (microsomes, mitochondria and leukocyte NADPH oxidase), an elevation in NO-synthase activity due to the inducible isoenzyme whilst under the decreased activity of the constitutive isoform with its transition to the uncoupled state, and a growth in the concentration of peroxynitrite. The introduction of specific modulators of the transcription factors NF-κB and Nrf2 (ammonium pyrrolidine dithiocarbamate and dimethylfumarate, respectively) after TBI modelling significantly reduces the signs of oxidative-nitrosative stress in the periodontal soft tissues at the end of the early post-traumatic period (on the 7th day): it restricts the production of the superoxide anion radical, reduces NO-synthase activity due to the inducible isoform of this enzyme, enhances the activity and coupling of cNOS, and decreases the concentration of peroxynitrite.

ROLE OF SPECIFIC TRANSCRIPTION FACTORS NF-κB AND NRF2 IN MECHANISMS OF DEVELOPMENT OF BRAIN-INJURY INDUCED OXIDATIVE AND NITROSATIVE STRESS

Nazarenko¹,

Kostenko²

2022

Effect of Curcumin on Lipid Peroxidation in the Rat Brain Under Conditions of Round-the-Clock Illumination and High-Calorie Carbohydrate-Lipid Diet

Frankel

Zyuzin

Черно

2023

The aim of this study is to assess the effect of the polyphenol curcumin on lipid peroxidation (LPO) in the homogenate of the cerebral hemispheres from rats exposed to the round-the-clock lighting (RCL) and kept on high-calorie carbohydrate-lipid diet (HCCLD). The experiments were performed on 21 white male Wistar rats weighing 210-250 g, divided into 3 groups of 7 animals each. Animals of group 1 (control I) were kept on a standard vivarium diet and equal alternation of light and darkness periods. Rats of groups 2 and 3 during the period of RCL in the setting of HCCLD were daily injected 1 ml of 20% aqueous fructose solution intragastrically through a probe ("placebo", control II) and curcumin in a dose of 200 mg/kg, respectively. The level of lipid peroxidation in the cerebral homogenate was assessed by the formation of a colored trimethine complex in the reaction with thiobarbituric acid (TBA). Keeping rats on the RCL and HCCLD was accompanied by a significant increase in the concentration of TBA reactants before and after the incubation in pro-oxidant buffer solution, by 59.0 and 68.8%, respectively. The administration of curcumin under the experimental conditions significantly reduced the concentration of TBA-active products: before its incubation in the pro-oxidant buffer solution – by 24.4%, after the incubation – by 31.0% compared to the corresponding values in the 2nd group. This enables us to conclude that the administration of the polyphenol curcumin under exposing rats to RCL and keeping them on HCCLD significantly limits the LPO development in the cerebral homogenate of the cerebral hemispheres.

The Effect of Nf-Κb on the Intensity of Oxidative Stress in the Cerebral Cortex of Rats Under the Combined Influence of the Light-Dark Cycle, Systemic Inflammatory Response, and Sodium Glutamate Administration

Volkova,

Kostenko

2024

To date, scientists have confirmed the link between the development of oxidative stress and disruptions in the light regime, as well as the systemic inflammatory response. The impact of monosodium glutamate on increasing oxidative damage to rat brain tissue has also been identified. The aim of this study was to investigate the role of the transcription factor NF-κB by examining the effect of its inhibitor, ammonium pyrrolidinedithiocarbamate, on the development of oxidative stress in the cerebral hemispheres of rats, in combination with acute desynchronosis, systemic inflammatory response, and monosodium glutamate administration. The study was conducted on 45 white Wistar rats weighing 150-200 g, divided into three groups: control (n=15), a group subjected to a combination of acute desynchronosis, systemic inflammatory response, and sodium glutamate administration (n=15), and a group exposed to the combination of acute desynchronosis, systemic inflammatory response, and received sodium glutamate and pyrrolidinedithiocarbamate (n=15). To induce acute desynchronosis, the rats were initially kept under a regular light-dark cycle (12 hours of light, 12 hours of darkness) for 3 weeks, followed by a shift in the light-dark phases by 6 hours back over the next 3 days. The systemic inflammatory response was modeled through intraperitoneal administration of Salmonella typhi lipopolysaccharide. During the first week, lipopolysaccharide was administered three times at a dose of 0.4 μg per 1 kg of body weight, and during the following seven weeks, it was given once a week. Sodium glutamate, at a dose of 30 mg/kg, dissolved in 0.5 ml of distilled water, was administered intragastrically for 20 days. The NF-kB activation inhibitor ammonium pyrrolidinedithiocarbamate (Sigma-Aldrich, Inc., USA) was administered at a dose of 76 mg/kg three times a week for 20 days. In a 10% homogenate of the cerebral hemispheres, the following were measured: the rate of superoxide anion radical production, the content of thiobarbituric acid-reactive substances (TBARS), the increase in these parameters, as well as the activity of catalase and superoxide dismutase. Administration of pyrrolidinedithiocarbamate in combination with acute desynchronosis, systemic inflammatory response, and sodium glutamate reduced the rate of basic superoxide anion radical production by 10%, NADPH-induced production by 17.6%, NADH-induced production by 13%, reduced the concentration and growth of TBC-active products by 6.6% and 14.6%, respectively, increased the activity of superoxide dismutase by 35.2%, catalase by 10.5% compared to the group exposed to the combination of acute desynchronosis, systemic inflammatory response, and sodium glutamate administration. Conclusion. The administration of pyrrolidinedithiocarbamate in combination with a systemic inflammatory response, acute desynchronosis and the action of sodium glutamate reduces the production of the superoxide anion radical, the concentration and increase in TBC-active products, enhances antioxidant protection that indicates the possible influence of the nuclear factor NF-κB on the development of oxidative processes in the cerebral hemispheres of rats.