The effect of new partially hydrogenated pyridines, cyanothioacetamide derivatives, on the liver morphological parameters in rats with dexamethasone-induced diabetes mellitus

Introduction. On the basis of the Chemex Scientific Lab of the Vladimir Dahl Lugansk State University we have synthesized and selected 4 samples of partially hydrogenated pyridine derivatives via in silico screening, containing a furan fragment in the fourth position (codenamed cv-150, cv-140, cv-083 and jen09-039), the effect of which on the course of dexamethasone-induced diabetes mellitus (DM) is of interest.

Aim. To study the morphological parameters of the liver of dexamethasone-induced diabetic rats during a period of pronounced senile changes in the setting of pharmacological treatment with new partially hydrogenated pyridines, cyanothioacetamide derivatives.

Materials and methods. The experiment was carried out with 92 18-month-old albino male rats, by administering per os 4 samples of 1,4-dihydropyridine at a dose of 1 mg/kg to each individual group of animals with dexamethasone-induced diabetes mellitus. Simultaneously, a control group (dexamethasone-induced diabetes) and a group of intact animals (without steroid-induced diabetes) were used. Dexamethasone was administered for 13 days. The intact and control group of animals consisted of 12 individuals. Four experimental groups of animals consisted of 17 individuals in each group. Animals of the experimental groups received one of the study compounds cv-150, cv-140, cv-083 and jen09-039 via gastric tube at a dose of 1 mg/kg body weight for 21 days.

Results. During the experiment, 10 animals died from late complications of DM. Death was recorded in the control and experimental groups treated with cv-083 and jen09-039 compounds. The most pronounced hepatomegaly was found in animals of the control group, the absolute liver weight averaged 16.43 g (3.4% of body weight) with indicators in intact animals group of 14.44 g (2.8% of body weight). The liver weight of rats treated with the cv-150 compound was 12.90 g (2.74% of body weight). The minimal number of pathological changes of the liver was detected in animals receiving partially hydrogenated pyridine cv-083 – 28.6%. The maximum number of pathological changes was registered in control animals receiving dexamethasone without pharmacological treatment – 88.9%. No liver changes were detected in intact rats.

Conclusion. Positive metabolic and psychosomatic changes were observed during the experiment in groups of animals treated with cv-150 and cv-140 compounds. There was no mortality in these experimental groups. According to necroptic study, hepatoprotective activity was found in these compounds. The result of using the cv-083 compound is questionable. The jen09-039 compound did not have any positive effect on the course of dexamethasone-induced diabetes.

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