The influence of monosodium glutamate on the development of oxidative-nitrosative stress in the large cerebral hemispheres of rats under the combination of a change in the “light-dark” cycle and a systemic inflammatory response

Abstract

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.