Morphofunctional State of the Liver Under Conditions of Three-Month Dark Deprivation: The Influence of Circadian Disruptions and Melatonin

Disruption of circadian rhythms caused by constant artificial lighting ("light pollution") is a significant risk factor for the development of metabolic and age-associated pathologies. The liver, as a central metabolic organ with pronounced circadian regulation of its functions, is particularly vulnerable to desynchronosis. The aim of this study was to evaluate the effect of three-month dark deprivation (constant lighting) and the corrective action of exogenous melatonin on the morphofunctional state of the liver in young mature rats. The experiment used 3-month-old male Wistar rats, divided into groups: control (standard light:dark cycle 10:14 h), dark deprivation group (DD, constant lighting 24 h/day), and DD + Melatonin group (DD + Mel, dark deprivation with melatonin administered in drinking water at a dose of 12 mg/L). After 3 months (animal age 6 months), a comprehensive analysis was performed. It was shown that dark deprivation causes a profound (more than five-fold) suppression of plasma melatonin levels, which is accompanied by the formation of a pro-senescent and metabolically dysfunctional phenotype of the liver. This was manifested by the development of steatosis, an 18% increase in hepatocyte area, a 30% decrease in the proportion of binucleated hepatocytes, activation of cellular senescence markers (p16, p21) and stress markers (p53), and suppression of the expression of circadian transcription factors BMAL1 and CLOCK. At the ultrastructural level, lipofuscin accumulation, damage to mitochondria and the Golgi apparatus were noted. Biochemically, hyperglycemia, increased AST activity, hypoproteinemia, hypoalbuminemia, hypercholesterolemia, and hypertriglyceridemia were revealed. Administration of exogenous melatonin completely prevented the development of these disorders, normalizing hormone levels, morphology, ultrastructure, biochemical parameters, and the expression of key molecular markers. Thus, three-month dark deprivation induces complex pro-senescent remodeling and metabolic dysfunction of the liver, mediated by melatonin deficiency, while exogenous melatonin demonstrates a pronounced hepatoprotective and chronoprotective effect.