Effect of melatonin on the state of oxidative stress in metabolic syndrome

Abstract

The metabolic syndrome (MetS) is a combination of several interrelated cardiometabolic risk factors, such as abdominal obesity, impaired glucose tolerance/hyperglycemia, dyslipoproteinemia, and prothrombotic and proinflammatory conditions. Oxidative stress (OS), which occurs as a result of excessive intracellular accumulation of reactive oxygen and nitrogen species and other free radicals, contributes to the development of obesity, MetS, metabolic dysfunction-related steatotic liver disease, metabolic cardiomyopathy, and type 2 diabetes mellitus. Enhanced OS leads to accelerated formation of protein glycation end products, which initiates a cascade of pathophysiological signaling pathways with the formation of proinflammatory cytokines and thus further activates the OS. In order to optimize the negative effects of free radicals, antioxidants are widely used, a special place among which is occupied by the pineal hormone melatonin (MEL). The neurohormone has direct, indirect and receptor-mediated effects. In particular, MEL and its metabolites are direct scavengers of most free radicals in cells, with a certain specific affinity for substrates. MEL is more effective in scavenging hydroxyl radicals and reduces lipid peroxidation during oxidative challenges, probably by delaying its initiation rather than directly scavenging peroxide radicals. MEL restores redox balance by activating antioxidant enzymes and inhibiting prooxidant enzymes, lipoxygenases and probably quinone reductase 2, activating mRNA of antioxidant enzymes and increasing intracellular glutathione. However, the peculiarities of the effect of MEL on the course of MetS and comorbidities remain unclear. The purpose of this review is to elucidate the peculiarities of the mechanisms of antioxidant effect of MEL in MetS, as well as to analyze the data from experimental studies and clinical trials.