Effect of incretin mimetics and incretin enhancers on wound healing in albino wistar rats

Abstract

Wound being one of the common clinical entities ,often challenges the clinicians when associated with non diabetic foot ulcer .Insulin, in addition to its hypoglycaemic activity is known to promote wound healing by increasing cellular proliferation, mineralization of the tissue, angiogenesis and decreased apoptosis in wound. Incretin mimetic and incretin enhancer apart from its antidiabetic property has been reported to increase angiogenesis and promote wound healing in diabetic foot ulcer . Angiogenesis is required for wound healing hence, any drug which promotes angiogenesis will promote healing. Sitagliptin and linagliptin by its virtue of its effect on angiogenesis could be expected to promote healing in non- diabetic rats. There are controversial reports regarding on angiogenesis. There is scanty information about DPP-4 inhibitors on wound healing in normal rats. Paucity of such information, the present study was planned to explore the influence of incretin mimetics and incretin enhancers on excision and incision wounds in euglycemic male Wister rats. newline newlineMethodology: newlineAnimal models were used with wound induced in rats. Excision wounds were made as described by excising the full thickness circular skin (approximately 500mm2) from the nape of the neck under halothane anaesthesia. A total of 56 wistar albino rats weighing 250-300 grams were selected. Four Drugs were given orally and two drugs subcutaneous every day for 16 days. Wounds were monitored by planimetry. Scar shape and size were noted on complete epithelization,inflammation and tissue remodeling. ELISA kits was used to measure tumor necrosis factor alpha (TNF alpha), interleukin-6 (IL-6), induciable nitric oxide synthase (iNOS), hydroxyproline (HYP). Histopathological examination of healed wound area was also carried out. newlineResults: newlineSitagliptin and linagliptin significantly enhanced healing in all the wound models as compared to controls while other drugs like exentide, liragluitide, saxagliptin and vildagliptin did not show any effects on healing. newlineHistopathological examination of healed wound area was carried out on 8th day. Wound enclosure was found to be smaller in sitagliptin and linagliptin groups; granulation tissue showed comparatively less inflammatory cells, more collagen, fibroblast and proliferating capillaries than control group. newline ELISA kits showed HYP (hydroxyproline) and iNOS were increased, IL-6 and TNF alpha were decreased. The blood glucose was 100 mg/dl in sitagliptin and 105 mg/dl in linagliptin groups. newlineConclusion: newlineThe present study reveals that sitagliptin and linagliptin have anti-inflammatory and immune modulatory activities during wound healing. newline newline