V.P. Kotegov, A.V. Skalny, J.A. Brudastov, A.V., Suldin, J.G. Malkova

The purpose of the research - to study the effect of prolonged administration of zinc sulfate monohydrate on glucose tolerance, hypoglycemic effect of insulin, hyperglycemic effect of adrenaline, acute and chronic alcoholization of rats. Experiments were carried out on white nonlinear male rats with mass 250-270 g. Zinc sulfate monohydrate was administered at 1 % starch mucus daily orally at 3 mg / kg a) intact animals during 1 month and b) animals with steroid diabetes during 15 days. Steroid diabetes was induced by daily intramuscular injection of dexamethasone phosphate at the rate of 100 mg / kg for 15 days. In a control experiment only starch mucus was used in equivolume amounts. At the end of the study the character of the glycemic curve of rats was studied by oral glucose load and also with free access to food. The concentration of glucose in the blood was determined by the glucose oxidase method at discrete time intervals. Glucose solution was injected once at the rate of 2 g / kg, food with high content of carbohydrate was given every 2 hours. As standard drugs we used a derivative of biguanide (metformin, «Siofor», Berlin-Chemie) and the derivative of sulfonylurea (gliclazide, «Diabeton», Servier). Also at the end of the experiment hypoglycemic effect of insulin and hyperglycemic action of adrenaline were studied. Insulin («Actrapid») was introduced intraperitoneally once at dose 1.0 IU/kg. Solution of 0.1 % adrenaline hydrochloride was injected intramuscularly at a dose of 0.5 mg / kg. In order to determine parameters of toximeter 40% ethyl alcohol was administered intact rats intragastrically by atraumatic metallic probe at a dose that was gradually increased from 5000 to 17500 mg / kg. Large doses was introduced repeatedly during 15 minutes. This group was the control. Zinc sulfate was introduced to animals of experimental series during the months by orally 3 mg / kg. When modeling the chronic alcoholization of rats 15% solution of ethyl alcohol instead of water was provided within 30 days and also the daily zinc sulfate was administrated at the rate of 3 mg / kg. At the end of the experiment ability to learn of animals was evaluated by the development of passive avoidance, biochemical blood analysis was performed. It is shown that zinc sulphate monohydrate for intact rats and rats with steroid diabetes significantly improves tolerance to oral glucose load, increases the hypoglycemic effect of insulin, reduces adrenaline hyperglycemia. Prolonged administration of zinc sulfate monohydrate in acute alcohol intoxication of rats reduces the magnitude of mean lethal dose of ethyl alcohol on 20 %. In rats that were given 15 % ethanol during month, zinc sulphate monohydrate improves to normal blood levels of albumin, glucose and total cholesterol, lowers indicators thymol test, helps to preserve the memorable track for testing animals in the installation of «light-dark chamber». It is concluded that zinc sulfate monohydrate in long-term administration exhibits antidiabetic activity, reduces acute and chronic toxicity of ethyl alcohol. These effects of the drug may be due to increased metabolism of ethyl alcohol by activation of the zinc-containing enzymes alcohol dehydrogenase and catalase, improving the effects of insulin in all phases of its biological actions, such as the synthesis, deposition, separation, transport in the blood, the connection to the receptors, the activation of glycogen synthesis in the liver and inhibition of catecholamine biosynthesis.

 

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