ИНДУКЦИЯ ТРАНСКРИПЦИОННОГО ФАКТОРА NRF2 УГНЕТАЕТ ПРОДУКЦИЮ АКТИВНЫХ ФОРМ КИСЛОРОДА И АЗОТА В ПЕЧЕНИ КРЫС ПРИ МОДЕЛИРОВАНИИ МЕТАБОЛИЧЕСКОГО СИНДРОМА В УСЛОВИЯХ КРУГЛОСУТОЧНОГО ОСВЕЩЕНИЯ

Abstract

Aim: To evaluate the effect of dimethyl fumarate, an Nrf2 inducer, on the production of reactive oxygen and nitrogen species in the liver of rats when modeling metabolic syndrome under round-the-clock lighting. Material and methods. Dimethyl fumarate in a 10% dimethyl sulfoxide solution at a dose of 15 mg/kg was administered intraperitoneally to white rats while modeling the metabolic syndrome (a 20% aqueous fructose solution for drinking and a diet enriched with carbohydrates and lipids). The rate of generation of the superoxide anion radical (•О ), the activity of total NO synthase (NOS) as well as its constitutive and inducible isoforms (cNOS, iNOS), the content of peroxynitrites of alkali and alkaline earth metals were determined in the liver homogenate of rats. Results. The administration of dimethyl fumarate under the experimental conditions significantly restrained the •О production in the liver tissues by microsomes and NOS – by 48.9%, by mitochondria – by 47.3%, by leukocyte NADPH oxidase – by 45.6%; it also reduced NOS activity (total and iNOS) by 33.1% and 35.9%, respectively, and the concentration of peroxynitrites by 39.7% as compared with the values of the control group which received only the solvent (10% dimethyl sulfoxide solution). The cNOS activity and coupling index exceeded the control group result 2.95 and 5.5 times, respectively. Conclusion. The administration of dimethyl fumarate, an Nrf2 inductor, to rats during the simulation of the metabolic syndrome by round-the-clock lighting is an effective means of limiting the production of reactive oxygen and nitrogen species in the liver tissues.