Effect of Vildagliptin on the Level of P-Glycoprotein Expression in Normal Conditions and Alloxan–Induced Type 2 Diabetes Mellitus
Journal: I.P. Pavlov Russian Medical Biological Herald (Vol.30, No. 1)Publication Date: 2022-03-31
Authors : D. S. Titov; S. K. Pravkin; A. A. Nikiforov; E. S. Savost'yanova; M. A. Maystrenko;
Page : 29-38
Keywords : P-glycoprotein; vildagliptin; type 2 diabetes mellitus;
Abstract
INTRODUCTION: Vildagliptin is one of the drugs of choice in the treatment of type 2 diabetes mellitus (DM). In the literature review, no study has reported the effect of vildagliptin on the expression level of the transporter protein P-glycoprotein (P-gp, ABCB1 protein). AIM: To assess the in vivo effects of vildagliptin on the level of Р-gp expression in normal conditions and experimental alloxan-induced type 2 DM. MATERIALS AND METHODS: Type 2 DM was induced by a single intravenous injection of freshly prepared alloxan monohydrate solution in citrate buffer (pH = 4.0) at a dose of 80 mg/kg. Glucose content (mmol/L) was determined by the glucose oxidase method using Human kit (Germany) and insulin content (µU/mL) by radioimmunoassay technique using Immunotech kit (Czech Republic). As an express method for the determination of glucose levels in the whole blood, OneTouch UltraEasy electrochemical glucose monitor (USA) was used. The level of P-gp expression in rabbit tissues (i.e., jejunum, liver, kidney, and cerebral cortex) was evaluated by the indirect histochemical method. After preliminary treatment, the histological material was embedded in paraffin. Antigens were retrieved before the immune-staining reaction. Then, the sections were incubated with primary antibodies to P-gp (ABCB1 antibody, middle region; 0.1 mL [Aviva Systems Biology ARP51326-P050, USА]). For immune staining, a polymer detection system with a peroxidase label (Leica Microsystems, Germany) was used. The cell nuclei were stained with hematoxylin. Photos of the micropreparation were captured using Canon Power Shot G5 digital camera with 400× magnification. Digital images were analyzed and processed using ImageJ and IHC Profiler plugin designed for quantitative immunohistochemical analysis. The results obtained from healthy animals, animals with alloxan-induced DM, healthy animals administered vildagliptin, and animals with modeled DM administered vildagliptin were compared. RESULTS: After day 14 of administration to healthy rabbits and day 5 of vildagliptin discontinuation (5 mg/kg), no statistically significant changes in P-gp expression in the aforementioned tissues and the levels of basal and postprandial insulin and blood glucose were noted. After the 14-day therapy of alloxan-induced type 2 DM with vildagliptin (5 mg/kg), a statistically significant recovery of expression of the P-gp expression in the jejunum, liver, and kidney was reduced due to the underlying pathology. In addition, the values of healthy rabbits and statistically significant normalization of the insulin and blood glucose levels were observed. On day 5 of drug cancellation, significant inhibition of P-gp expression in the jejunum, liver, and kidney was noted again, and there was a significant reduction of postprandial insulin and blood glucose. No significant alterations of ABCB1 protein expression in the hematoencephalic barrier were noted during the studied periods. CONCLUSION: The administration of vildagliptin (5 mg/kg) to rabbits with alloxan-induced type 2 DM promotes the recovery of P-gp expression in the jejunum, liver, and kidney, which were reduced due to the underlying pathology. Meanwhile, its administration to healthy animals had no significant effect on the expression of P-gp.
Other Latest Articles
- Parameters of B-Cell Immunity and Their Diagnostic Significance in Preeclampsia of Different Severities
- Changes in the Deformability and Resistance of Erythrocyte Membranes under the Action of Gamma-Aminobutyric Acid Derivatives in the Offspring of Rats with Experimental Preeclampsia
- Syntopy of Pulmonary Vein Orifices in the Left Atrium of the Human Heart
- P. K. Anokhin’s answer to E. A. Asratyan’s review of “Biology and neurophysiology of conditioned reflex” monograph. Echo of Pavlovian session
- Success and unsolved issues of embolization of the uterine arteries in uterine fibroid
Last modified: 2023-04-03 23:05:25