Therapeutic Effects of Canagliflozin and Zinc Sulphate Alone and in Combination on Pancreatic Histology in Type-2 Diabetic Rat Model

Bushra Suhail

doi:10.47489/p000s343z7591-6mc

Abstract

Introduction: Diabetes Mellitus is a common metabolic syndrome characterized by persistently elevated blood glucose levels. Canagliflozin is an SGLT-2 inhibitor that controls hyperglycemia by reducing the reabsorption of filtered glucose and excreting it in the urine. Zinc sulphate exhibits some beneficial role in diabetes mellitus but has not been compared to canagliflozin individually and in combination. Aims & Objectives: To observe the effects of treatment with canagliflozin and zinc sulphate on pancreatic histology in streptozotocin induced type-2 diabetic rat model. Place and duration of study: The study was conducted in the Department of Pharmacology, KEMU and PGMI, Lahore for the period of two months. Material & Methods: It was an animal experimental study of eight weeks duration in which 48 adult healthy albino rats of male gender were divided into six groups and were provided the high fat diet throughout the study period. Groups A and B were maintained as healthy and diseased controls respectively. Groups B, C, D, E and F were administered single I/P dose streptozotocin (35mg/kg) at day 22 for inducing diabetes. Upon confirmation of diabetes after a week the rats were further treated as per group designation orally for 4 weeks , individually or in combination with full or half doses of canagliflozin (10 mg /kg/day, 5mg/kg/day ) and zinc sulphate (30mg/kg/day, 15mg/kg/day) . All animals were euthanized at the completion of study duration. The pancreatic tissue was taken out and examined for the histopathological changes (size and number of pancreatic islets, karyolysis and ballooning degeneration). Results: There was a marked improvement in the size and number of islets as well as the inflammatory changes in the combined treatment group (with canagliflozin in full as well as half dose of zinc sulphate) as compared to the groups given zinc sulphate and canagliflozin separately. Conclusion: Combined treatment with canagliflozin and zinc sulphate has a better protective effect on the pancreatic tissue in diabetes than either of them used alone.

Highlights

Diabetes Mellitus is a common metabolic syndrome characterized by persistently elevated blood glucose levels
Canagliflozin, which belongs to the class of SGLT-2 inhibitors seems to be a good option since it is well-tolerated in the body and has additional benefits of lowering blood pressure and body weight
A significant restoration of the size of islets as well as the reversal of karyolysis and ballooning degeneration was observed on histopathological examination, whereas no significant difference was observed in the number of islets with zinc treatment

Summary

Introduction

Diabetes Mellitus is a common metabolic syndrome characterized by persistently elevated blood glucose levels. There has been an alarming increase in the number of individuals having diabetes during the last two decades, which poses a threat to increase the health expenditure for diabetes worldwide and in the developing countries, where the rate of rise is more.[1,2] The current treatment options provide control of hyperglycemia but the associated side effects worsen the patient’s compliance, so there is a dire need of a therapy which can provide a good glycemic control with minimal side effects.[3] In this regard, canagliflozin, which belongs to the class of SGLT-2 inhibitors seems to be a good option since it is well-tolerated in the body and has additional benefits of lowering blood pressure and body weight It promotes urinary excretion of glucose via decreasing its reabsorption at the proximal tubule and causing a reduction in the renal glucose threshold.[4] Zinc regulates the functions of many tissues and has the potential to normalize the hyperglycemia.[5] Limited studies have shown the efficacy of zinc combined with oral hypoglycemic agents in combating diabetes mellitus.[6] The high-fat diet/streptozotocin (HFD/STZ) rat model is an example of the experimentally induced type 2 diabetes model. It is prepared by combining a fatrich diet to produce insulin resistance and treating with STZ (a toxin of the beta cells), that leads to greater decrease in the functional mass of the pancreatic beta cells.[7]

Methods

Results

Conclusion