Effect of dipeptidyl peptidase 4 inhibitors on acute and subacute models of inflammation in male Wistar rats: An experimental study

Abstract

Introduction: The prevalence of Type 2 diabetes mellitus (T2DM) has reached alarming proportions due to the rapidly increasing rates of this disease worldwide. Preclinical and clinical studies have revealed elevated levels of inflammatory markers in a vast number of illnesses such as T2DM, obesity, and atherothrombosis collectively called metabolic syndrome leading to adverse cardiovascular events. Dipeptidyl peptidase 4 (DPP-4) inhibitors which are the enhancers of glucagon-like peptide 1 (GLP -1), could have anti-inflammatory potential which could help in reducing cardiovascular complications of diabetes and benefit patients suffering from the metabolic syndrome.

Objective: The objective of this study was to analyze the effect of DPP-4 inhibitors, namely vildagliptin and saxagliptin on acute and subacute models of inflammation.

Materials and methods: Male Wistar rats were randomly divided into control, standard, and two treatment groups (6 animals in each group, total 24 animals). The animals received the drugs orally. The effects of vildagliptin and saxagliptin on inflammation were tested in acute (carrageenan-induced paw edema method) and subacute (grass pith and cotton pellet implantation method) models of inflammation.

Results: Vildagliptin and saxagliptin used in the present study showed a significant anti-inflammatory activity in acute and subacute models of inflammation.

Conclusion: The present study suggests that vildagliptin and saxagliptin have significant anti-inflammatory potential. Based on the findings of the present study and the available literature, it can be concluded that the anti-inflammatory potential of DPP-4 inhibitors could help to reduce the cardiovascular complications of Type 2 diabetes and the related cluster of metabolic disorders collectively called the metabolic syndrome.

Keywords: Inflammation; saxagliptin; vildagliptin.

Figure 1

Effect of various treatments on carrageenan-induced rat paw edema

Figure 2

Photomicrographs of grass pith with granulation tissue. (a) Control group; (b) aspirin group; (c) vildagliptin group; (d) saxagliptin. As compared to control group; aspirin-, vildagliptin- and saxagliptin-treated groups show reduced number of fibroblasts, decreased granulation tissue, collagen content, and fibrous tissue (H and E, ×40)