MELATONIN IMPROVES SPLEEN HISTOPHYSIOLOGY OF RATS WITH DIET-INDUCED OBESITY: CHRONOTHERAPY APPROACH

One of the most commoncharacteristics of obesity is the development of a systemic low-grade proinflammatory state in the entire body, including the immune organs. Spleen enlargement during diet-induced obesity contributes to the development of chronic inflammation. Melatonin due to immunomodulatory, antioxidant, and systemic metabolic rolesis proposed to be an effective candidate for anti-obesity therapy. As immune systems demonstrate pronounced circadian rhythmicity and immune cells have different types of melatonin receptors, a chronotherapeutic approach might be used to choose the most effective regimes of melatonin administration for the correction of obesity-provoked damage to the spleen. Thus, the main goal of our research was the analysis of the rats' spleen histophysiology during the development of high-calorie diet-inducedobesity (HCD) after administering melatonin daily at different times (morning or evening). Melatonin was administered by gavage for 7 weeks in the dose of 30 mg/kg 1 h before lights-off (HCD ZT11, M ZT11, evening), or 1 h after lights-on (HCD ZT01, M ZT01, morning). For assessment of the morpho-functional state of the spleen,the histopathological evaluation of red and white pulp in different zones of lymphoid follicles was implemented. It was observed that obesity development wasaccompaniedbyhyperemia and vessel dilatation in the red pulp; while in the white pulp notable deformation of germinal centers and destroyed borders between zones of lymphoid follicles were noticed.The HCD group demonstrated a decrease inthe relative amount of the white pulp, the crosssectional area of germinal centers, and the cross-sectional area of the marginal zone; whilethe increased relative amount of red pulp and marginal zone/germinal centers ratiowere detected compared with control. Melatonin administration to obese rats increases the relative amount of the white pulp (HCD ZT11 group), the cross-sectional area of germinal centers (HCD ZT01 and HCD ZT11 groups), and the cross-sectional area of the marginal zone (HCD ZT11 group), and decreasesmarginal zone/germinal centers ratio (HCD ZT01 group) in comparison with the HCD group.Also,it was demonstrated that a choice between the morning or evening regimes of the melatonin treatment did not affect the histophysiology of the spleen in rats receivingthe standard diet (M ZT01 and M ZT11 groups). These results indicate that melatonin can be considered to be a powerful potential therapeutic agent for the amelioration of obesity-induced changes in the spleen.