The Efficacy of Canagliflozin on Type 2 Diabetic Nephropathy in Male Rats

Mourad, Manal M.G.; Ali, Fares E.M; Fadel, Sabah A.; Ellisy, Reham A.M.

doi:10.21608/svuijm.2023.234622.1685

The Efficacy of Canagliflozin on Type 2 Diabetic Nephropathy in Male Rats

Document Type : Original research articles

Authors

¹ Department of Medical Pharmacology, Faculty of Medicine, South Valley University, Qena, Egypt

² Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University ( Assiut Branch), Assiut, Egypt.

³ Department of Pathology, Faculty of Medicine, Assiut University, Assiut, Egypt.

10.21608/svuijm.2023.234622.1685

Abstract

Background: Sodium-glucose Cotransporter-2 inhibitors [SGLT2Is] are new antidiabetic group. Canagliflozin is the first member in this drug class approved for management of patient with type 2 diabetes (T2DM), that affects reabsorption of glucose from kidney, but its impact on kidney structure and function has not been clarified.
Objectives: The target of this study is assessment of the canagliflozin effect on body weight, blood glucose, serum creatinine, urea and evaluation of the possibility of urinary tract infection (UTI) development in type 2 diabetic rats.
Materials and Methods: The search was carried out on 24 male Wistar rats of weighting 160-300 g and ageing 2.5-3 months. They were splitted into 3 equal groups each of eight rats: negative control, positive control (diabetic) and Diabetic-canagliflozin treated groups. The positive control group was given a single dose intraperitoneal (IP) Streptzotocin (STZ) (35mg/kg diluted in 1ml of 0.1 M citrate buffer in 4.5 PH). The diabetic-canagliflozin treated group which received STZ was given canagliflozin (30 mg/kg/day, orally) for 12 weeks. Blood samples were collected and used for estimation of blood glucose, creatinine and urea levels. Urine samples were collected for urine analysis and urinary albumin creatinine ratio assessment. Kidney tissue samples were obtained for histopathological screening.
Results: Diabetic-canagliflozin treated group had highly significantly decrease in body weight (287 ± 34.6) in comparison with positive control group (309.3 ± 21.1) at the end of the study as their weight were (234.2 ± 15.7 and 232.2 ± 11.01, respectively) at the srart. In addition to the highly significant decrease in blood glucose (255 ± 5.7) in Canagliflozin-treated group after treatment compared to (515.7 ± 49.2) before treatment. Also, there were a high significant decrease in urinary albumin (1.8 ± 0.2) and urinary albumine/creatinine ratio (1.1 ± 0.18) after treatment by canagliflozin. Adding to this, canagliflozin increase the level of urinary glucose excretion (875 ± 104) and development of UTIs (13.75 ± 3.5). However, no significant difference (p-value = 0.149) in serum creatinine or urea levels were detected (p-value = 0.112). Treatment with canagliflozin improved histological structure changes in the kidney.
Conclusions: Canagliflozin has a renoprotective effect. It improves renal tissue damage and decreases blood glucose levels.

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