The effect of the complex antidiabetic composition on the histostructure of the pancreas in rats under the conditions of dexamethasone-induced diabetes

Abstract

Researchers of the National University of Pharmacy (NUPh) have developed a pharmaceutical composition based on glibenclamide and metabolitotropic substances with the proven antioxidant, membrane-protective and hypolipidemic action. Aim. To study the effect of a new antidiabetic composition (NAC) on the pancreatic histological structure in rats under experimental dexamethasone-induced diabetes. Materials and methods. The experimental diabetes mellitus in rats was induced by dexamethasone in the dose of 150 mg/kg for 5 weeks against the background of a high-calorie diet. Rats were divided into the following groups: Group 1 – control pathology (n=10); Group 2 receiving the NAC in the dose of 4.0 mg/kg (n=10); Group 3 receiving the reference drug glibenclamide in the dose of 0.25 mg/kg (n=10). All data obtained were processed using methods of variation statistics. The microscopic examination was carried out under a Granum light microscope, photographing of microscopic images was performed with a Granum DSM 310digital video camera. Photos were processed on a Pentium 2.4 GHz computer using the Toup View program. Results. In animals of the control pathology group introduction of dexamethasone against the background of a hypercaloric diet led to a marked decrease in the optical density of pancreatic islets in the microslide (up to 11.4 ± 1.0), their uneven distribution in the lobes, and redistribution of the percentage ratio between the islets. The percentage of large islets increased by 2.4 times, the islets themselves were hypertrophied, often had an elongated shape. Pancreatic islets in the middle practically disappeared. Although not significantly, the share of small islets increased by 26.61 %. There were mosaic lesions of pancreatic islets. There were hypertrophic, dystrophic changes in some of them, or beta-cells in the state of necrosis. The widening of the lumen of the excretory ducts, and focal expressive perivascular sclerosis were observed. Introduction of the NAC against the background of the experimental dexamethasone-induced diabetes significantly inhibited destruction of the pancreas compared to the control pathology. The volume density of pancreatic islets increased (by 57.89 %), their shape was much more common. The share of large islets decreased by a factor of 4.4. The share of medium (by the number of beta cells) pancreatic islets was restored to the intact level. At the same time, small islets still occupied a rather high share – 37.5 %. Morphologically, the beta cells in islets were more complete. There no «budding» of small islets from the mother one, and the membrane between the islets. The signs of hypertrophy of islets were clearly reduced. There was no sclerosis in the interlobar connective tissue layers, perivascular sclerosis, and dilatation of ductula. Introduction of the reference drug glibenclamide in the dose of 0.25 mg/kg to a lesser degree normalized the histological structure of the pancreas than the NAC. Although the state of pancreatic beta cells in a significant number of islets was normal, some of them had signs of vacuolization. Some islets were not too clearly separated from the acinar parenchyma; there was necrobiosis of some beta cells. The morphometric analysis of islets showed that the relative proportion of small islets still remained elevated compared to the intact control and even higher than in the control pathology group (by 20 %) although not significantly. The bulk density of pancreatic islets in microslides increased by 61.40 %. Conclusions. A new antidiabetic composition based on glibenclamide and metabolitotropic substances has a corrective effect on the state of the endocrine apparatus of the pancreas of female rats, it leads to a marked increase in the total number of islets (primarily small and medium ones) compared to the control pathology, a visualized increase in morphologically more complete insulin cells. The NAC exhibits a significant protective effect on pancreatic cells.