CHANGES OF THE LIVER IN EXPERIMENTAL DIABETES AND ITS CORRECTION WITH LONG-ACTING INSULIN ANALOGUE AND S-ADENOSYL L-METHIONINE (ADEMETIONINE)

The issue of selective hepatoprotective therapy in diabetes mellitus, in particular, the morphologically confirmed effectiveness of ademetionine is poorly studied. Aim: after 56 days to establish the morphological state of the liver with the determination of the content of lipid inclusions in streptozotocin diabetes and its correction with long-acting insulin analogue and ademetionine with the peculiarities of its introduction in the experiment. Material and methods. For the experiment, 20 intact male rats were used, which were divided into the following groups (5 animals each): 1 – intact; 2B – with streptozotocin diabetes mellitus (SDM) and administration of insulin («Tresiba», Denmark) from the 14th day; 2C – SDM with insulin and ademetionine («Heptral», France). 3 – control. Pieces of the liver were fixed in formalin solution 10 %, sections were made from paraffin blocks, which were stained with hematoxylin and eosin. Determination of fatty inclusions was carried out on cryostat sections with an alkaline solution of Sudan III according to Herxheimer (in modification). Results. In subgroup 2B after 56 days of the experiment, the following alterations were observed: intensive violations on the part of the vascular wall, moderate changes in the architecture of the central zone, sometimes the endothelium of the central vein was completely destroyed, cellular infiltrates in the liver parenchyma, an increase in the number of fatty inclusions, remodelling of the portal triads and vessels. In contrast to the administration of only insulin, the additional introduction of ademetionine led to the following changes: less pronounced structural disorders of the central zone, desquamation of the vascular endothelium, discomplexation of the liver plates, a lower level of alterations of the portal triads and cellular infiltration around them. Various vascular disorders were less appreciabled. The optimal four-stage scheme: a starting dose of 4 mg/kg (1 week) with a gradual transition to a maintenance dose of 8 mg (administer for 3 weeks), a maximum maintenance dose of 12 mg/kg (the next 3 weeks), then increasing the dose to 16 mg if necessary, taking into account the individual sensitivity of the animal. After 28 days of using the ademetionine, an increase in the number of fatty inclusions was observed, therefore the maintenance dose of 8 mg/kg was changed to the maximum permissible – 12 mg/kg, which led to a positive effect. After 56 days of the research, the level of lipid inclusions was within normal limits. Conclusion. Streptozotocin-induced diabetes mellitus in rats, which is corrected with long-acting insulin analogue and ademetionine (with a gradual increase in the dose to 12 mg/kg) for 6 weeks, with additional administration of a hepatoprotector, a better morphological condition of the liver, its vessels, portal triads are observed. The level of lipid inclusions is noted practically corresponds to intact animals.