Effect of Exogenous Melatonin on the LYVE-1 Expression in Liver Sinusoids of $db/db$ Mice with Obesity and DM2

The effect of exogenous melatonin (MT) on the expression of LYVE-1 receptor (lymphatic vessel endothelial hyaluronan receptor 1) in endothelial cells (ECs) of liver sinusoids of female
$db/db$
mice with obesity and type 2 diabetes mellitus was studied. LYVE-1 immunohistochemical staining was performed using the indirect avidin-biotin peroxidase method. A morphometric analysis of the relative area and brightness (this parameter is inversely proportional to the marker concentration) of the receptor staining was carried out. Control and placebo db/db mice at 16 weeks of age, revealed insignificant LYVE-1 staining of the network of blood sinusoid capillaries in the periportal regions and especially in the intermediate zones of the hepatic lobules. Long-term MT administration to animals (intragastrically at a dose of 1 mg / kg of body weight in
$200\ \mu\mathrm{l}$
of distilled water from the 8th to the 16th week of life) contributed to an increase in the relative area of LYVE-1 expression in the liver sinusoidal cells. At the same time, the antioxidant properties of MT can play an important protective role. This hormone exerts antioxidant effects not only directly on the extracellular matrix, but also indirectly, maintaining the membrane organization and intracellular structures in the EC of sinusoids. As a result, MT can reduce the hypoxic state of ECs in liver sinusoidal capillaries and, as a consequence, reduce the degradation of high-molecular-weight hyaluronan and promote an increase in the expression area of the “free”, i.e. non-HA-bound LYVE receptor. This, in turn, may indicate the strengthening of the endothelial barrier of the organ.