INDUCTION OF NRF2 TRANSCTIPTION FACTOR INHIBITS FORMATION OF RACTIVE OXYGEN AND NITROGEN SPECIES IN LIVER OF RATS UNDER MODELLING METABOLIC SYNDROME BY EXPOSURE TO ROUND-THE-CLOCK LIGHTING

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 under the conditions of modeling the metabolic syndrome with roundthe-clock illumination. Dimethyl fumarate in 10% dimethyl sulfoxide solution in a dose of 15 mg/kg was administered intraperitoneally to white rats over the modeled metabolic syndrome (a 20% aqueous fructose solution for drinking and a diet enriched with carbohydrates and lipids). In the liver homogenate of rats, the rate of generation of the superoxide anion radical (•О 2 ), the activity of total NO synthase (NOS), its constitutive and inducible isoforms (cNOS, iNOS), and the content of peroxynitrites of alkali and alkaline earth metals were determined. The administration of dimethyl fumarate under the experimental conditions significantly restrained the •О 2 production by microsomes and NOS in the liver tissues 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% compared with the values of the control group that received only the solvent (10% dimethyl sulfoxide solution). The cNOS activity and coupling index exceeded the control result in 2.95 and 5.5 times, respectively. The introduction of the Nrf2 inductor, dimethyl fumarate, during the simulation of the metabolic syndrome by round-the-clock lighting to rats is an effective means of limiting the production of reactive oxygen and nitrogen species in the liver tissues.