Effect Of Selective Sodium Glucose Transporter (Sglt -2) Inhibitors - Dapagliflozin And Canagliflozin On Acute & Subacute Models Of Inflammation In Male Wistar Rats – An Experimental Study

Abstract

INTRODUCTION The primary objective of the presentstudy was to determine the effect of selective sodium glucose transporter (SGLT -2) inhibitors - dapagliflozin and canagliflozin on acute as well as subacute models of inflammation in male Wistar rats. The secondary objective was to study the effect of these drugs on inflammatory markers like TNF – α, IL-6. Materials and Methods: Two models of inflammation were used: 1. Acute inflammation (carrageenan induced rat paw edema) 2. Subacute inflammation (foreign body induced granuloma formation) Animals were divided into various, (n=6 in each) that received orally either vehicle, aspirin or subcutaneously any one of the test drug in clinically equivalent doses. Aspirin was given half an hour before, dapagliflozin and canagliflozin were given 1 hour before carrageenan injection respectively. The volume of edema was measured in millilitres (ml) with the help of digital plythesmometer at different hours and the change in the volume of edema in different treatment groups was estimated. In subacute model of inflammation, two sterile cotton pellets each of l0mg weight and grass piths measuring 25x2mm were randomly implanted subcutaneously, in the axilla and groin, through a small incision under thiopentone anaesthesia. The treatment was started on the day of implantation and was given every twenty-four hours for ten days in control, aspirin, dapagliflozin and canagliflozin group . On day eleven, 5ml blood was obtained through cardiac puncture for estimation of inflammatory cytokines like TNF-α and IL-6. The rats were sacrificed to obtain cotton pellets and grass piths. Mean granuloma dry weight of cotton pellets for different treatment groups was measured and percentage inhibition of granuloma dry weight was calculated. The sections of grass piths were stained with haematoxylin and eosin (H & E) for histopathological studies. Results: Dapagliflozin and canagliflozin did not reduce significantly the carrageenan induced inflammation in acute model. In subacute model, significant reduction in granuloma dry weight and inflammatory markers was not observed in the treatment groups. Also the treatment with dapagliflozin and canagliflozin did not decrease the granulation tissue formation, fibroblasts and collagen as revealed by Haematoxylin and Eosin stain. Conclusion: The present study exhibited dapagliflozin and canagliflozin did not exert significant anti-inflammatory effect in acute and subacute models of inflammation. The anti-inflammatory effect seen in previous studies could be attributed to their hypoglycemic effect and not direct anti-inflammatory effect. However, these findings need to be confirmed in inflammatory models in diabetic animals.