Abstract
The aim of our study was to determine the effect of diacamph hydrochloride, an original antihyperglycemic drug, on the cortisol content in the blood of animals with a combined model of diabetes mellitus and chronic stress. The experiment was performed on mature male rats. Diabetes mellitus of the 1-st type was modelled by a single injection of alloxan monohydrate (150 mg/kg subcutaneously) and chronic immobilization stress was induced by putting the animals into tight boxes for 16 hours daily over 15 days period beginning from the 11-th day after alloxan injection. It has been found that the concentration of cortisol in the blood plasma of animals of the control pathology group increased essentially as compared to the intact control group. The concentration increased from 77.51 ng/mol to 421.65 ng/mol, i.e. became 5.4 times higher (p<0.001). It indicates intensity of corticosteroid-mediated mechanisms of stress-response behaviour against the background of modelled diabetes mellitus. Taking contrainsular properties of corticosteroids into account such effect of prolonged immobilization against the background of diabetes mellitus should be considered to be particularly unfavourable. Diacamph hydrochloride (intraperitoneal injections of 25 mg/kg daily) not only reduced glycemia, but also was likely to decrease the blood cortisol content to 172.0 ng/ml on the average as compared to the value in the control pathology group (p<0.001). Bemithyl, a classical actoprotector, used as a reference drug (intraperitoneal injections of 50 mg/kg daily) was found to be statistically significantly inferior to diacamph hydrochloride (p<0.001) as it decreased the cortisol concentration only to 253.35 ng/ml on the average. The results testify stress-protective properties of diacamph hydrochloride under diabetes mellitus conditions and substantiate the prospects of its further studying as a potential adaptogenic and stress-protective drug. The mechanism of diacamph hydrochloride action is associated with its effect on endocrinous mechanisms of stress reaction.
Highlights
Tests were carried out in white non-pedigree male rats with the initial weight of 160-180 g
Group 3 consisted of rats with the DM and chronic immobilization stress (CIS) model; they were injected DH once a day in a conditionally effective dose of 25 mg/kg i.p. [3]
Rats were decapitated immediately after removal from the cases on the 15th day of immobilization and the cortisol content in blood plasma was determined by the immunoenzyme method using standard set CORTISOL KIT (Germany) on Hipson equipment (Czech Republic)
Summary
Tests were carried out in white non-pedigree male rats with the initial weight of 160-180 g. Glycemia should exceed 11 mmol/L, which confirms the development of the model DM [6] This group of animals was subjected to the effect of chronic immobilization stress (CIS) for 15 days [1]. Animals of this group were injected with 0.9% NaCl solution in the dose of 0.5 mg/kg intraperitoneally (i.p.). Group 3 consisted of rats with the DM and CIS model; they were injected DH once a day in a conditionally effective dose of 25 mg/kg i.p. The effect of diacamhp hydrochloride and bemithylum on the cortisol content in the rats’ blood with the diabetes mellitus model on the background of the immobilization stress (n=7)
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