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At present, the relevance of examining changes to the normal light-dark cycle is increasing, and the connection between the development of the systemic inflammatory response (SIR) and circadian rhythm disorders has been confirmed. The effects of antidepressants on the human body are also actively studied. The aim of this study was to investigate the effect of fluoxetine on oxidative stress in the rat cerebral hemispheres under conditions of acute desynchronosis (AD), systemic inflammatory response (SIR), and fluoxetine administration. Material and methods. The study was conducted on 44 white Wistar rats weighing 150-200 kg of various articles, divided into 3 groups: control (15), a combination of AD and SIR (14), and a combination of AD, SIR, and fluoxetine (15). To simulate AD, a normal "light-dark" cycle (12 hours of light, 12 hours of darkness) was formed for 3 weeks, and the next 3 days the "light-dark" phases were shifted back by 6 hours. SIR was reproduced via intraperitoneal injection of Salmonella typhi lipopolysaccharide in the first week of 0.4 μg/kg 3 times a week, and in the following seven weeks – once a week. Fluoxetine was administered intragastrically for 21 days at a dose of 10 mg/kg and dissolved in 0.5 ml of distilled water at room temperature. In 10% of the homogenate of the large hemispheres of the brain, the rate of production of superoxide anion radical (SAR), the content of products that react with thiobarbituric acid (TBA-reactants), their increase, and the activity of catalase and superoxide dismutase (SOD) were determined. Results. The administration of fluoxetine in combination with AD and SIR reduced the rate of basic SAR production by 35.4%, NADPH-induced production by 34%, increased NADH-induced production by 65%, decreased the concentration of TBA-reactants by 23.7% and their augmentation by 54.3%, increased the activity of SOD by 85.7% and catalase by 12.4% compared to the group of combination of SIR and AD. Conclusions. When fluoxetine is administered alongside AD and SIR, it results in reduced baseline and NADPH-induced SAR production, increased NADH-induced production, decreased accumulation of TBA-reactants, and enhanced antioxidant activity in the rat cerebral hemispheres.

The relevance of this study stems from the growing interest in the impact of acute desynchronosis (AD) on oxidative disorders and the insufficiently studied effect of flavonoids on these processes in kidney tissue. This study investigates the effect of quercetin on oxidative and nitrosative stress in rat kidney homogenate under AD and 3 lipopolysaccharide (LPS)-induced systemic inflammatory response (SIR). The animals were randomly divided into five groups: group 1 served as the control, group 2 underwent LPS-induced SIR modeling for 8 weeks, group 3 experienced AD reproduction by shifting the light-dark cycle 6 hours earlier for 7 days, group 4 underwent AD modeling during the last week of LPS-induced SIR, and rats in group 5 were administered a water-soluble form of quercetin (corvitin) intragastrically was administered at a dose of 200 mg/kg (20 mg/kg in terms of quercetin) daily during the AD modeling against LPS-induced SIR. It was found that the modeling of LPS-induced oxidative stress and AD significantly increased the rate of superoxide anion radical production in kidney homogenate by microsomal monooxygenases and NO synthase (NOS), mitochondrial respiratory chain, leukocyte NADPH oxidase, inducible NOS activity, and decreased the activity of the constitutive NOS isoform and its coupling index. Under AD modeling, the rate of superoxide anion radical production by leukocyte NADPH oxidase, total and inducible NOS activity was significantly lower compared with LPS-induced SIR. When modeling AD against the background of LPS-induced SIR, the production of superoxide anion radical by microsomes, mitochondria and leukocyte NADPH oxidase exceeded the respective results of group 2 by 15.9%, 16.0% and 38.5%, and group 3 by 24.4%, 17.5% and 74.6%. The inducible NOS activity was 22.9% higher compared to the value of group 2 and 93.4% higher in group 3, the concentration of peroxynitrites of alkali and alkaline earth metals was 35.5% higher than the respective parameters of group 2 and 57.9% higher than in group 3. Administration of quercetin during AD modeling and LPS-induced oxidative stress significantly reduced the rate of superoxide anion radical production by microsomal monooxygenases by 17.1%, mitochondrial respiratory chain by 31.2%, leukocyte NADPH oxidase by 19.4%, total and inducible NOS activity by 50.4% and 55.5%, respectively; the concentration of peroxynitrites of alkali and alkaline earth metals diminished by 41.4% compared to the value of group 4. It has been concluded that the administration of quercetin significantly reduces the signs of oxidative-nitrosative stress in the kidney homogenate of rats. [ABSTRACT FROM AUTHOR]

Today, the issue of the consequences of disrupting the normal “light-dark” cycle is becoming increasingly important, and the link between the development of a systemic inflammatory response (SIR) and circadian rhythm disorders has been confirmed. The effect of monosodium glutamate on the human body is being actively studied. The aim of the work was to find out the influence of monosodium glutamate on the development of oxidative-nitrosative stress in the homogenate of the large cerebral hemispheres of rats with a combination of acute desynchronosis (AD), SIR and administration of monosodium glutamate. Material and methods. The research was carried out on 72 white Wistar rats weighing 150–200 of different sexes, divided into 5 groups: control (n = 15), AD (n = 13), SIR (n = 15), a combination of SIR and AD (n = 14), a combination of SIR, AD, and glutamate (n = 15). To simulate AD, a normal “light-dark” cycle (12 hours of light, 12 hours of darkness) was formed for 3 weeks, and the next 3 days the “light-dark” phases were shifted back by 6 hours. SIR was reproduced by intraperitoneal injection of Salmonella typhi lipopolysaccharide in the first week at a dose of 0.4 μg/kg 3 times per week, the following seven weeks – once a week. Sodium glutamate was administered intragastrically for 20 days at a dose 30 mg/kg, dissolved in 0.5 ml of distilled water. In a 10 % homogenate of the large cerebral hemispheres, we determined the rate of superoxide anion radical (SAR) production, the content of products that react with thiobarbituric acid (TBA-reactants), their increase, activity of catalase, superoxide dismutase (SOD), ornithine decarboxylase (ODC), concentration of nitrites, peroxynitrites, total activity of NO-synthase (NOS), its constitutive (cNOS) and inducible (iNOS) isoforms. Results. In the group of SIR, AD and glutamate combination, compared to the control, the following was noted: an increase in the rate of basic production of SAR by 175.8 %, by the microsomal pathway by 20.0 %, by the mitochondrial pathway by 51.2 %, the concentration of TBA-reactants by 83.4 %, their increase – by 61.7 %, decrease in the activity of SOD by 57.1 %, catalase – by 38.1 %; an increase in peroxynitrite content by 116.7 %, ODC activity by 161.5 %, total NOS activity by 25.6 % and iNOS by 27.4 %, a decrease in cNOS activity by 15.0 % and nitrite concentration by 35.0 % in brain tissues. Conclusions. Sodium glutamate administration in combination with AD and SIR leads to increased oxidative-nitrosative stress, inhibition of antioxidant protection; contributes to the activation of the general activity of NO-synthase and iNOS, suppresses the activity of cNOS.