Canagliflozin Attenuates Hypertrophy, Oxidative Stress, and Lipid Profile through the Connective Tissue Growth Factor Pathway in Isoprenaline-induced Cardiac Injury
Govind Garg, Manju Gari, Meemansha Sharma, V A Aneesha, Anshuk Sharma, Madhu Cholenahalli Lingaraju, Subhashree Parida, Akhilesh Kumar, Vidya Singh, Sonal, Thakur Uttam SinghAbstract
Background:
Canagliflozin, a sodium–glucose cotransporter 2 (SGLT-2) inhibitor approved for type 2 diabetes, has been reported to confer cardiovascular protection beyond glycemic control.
Aim:
The present study was designed to investigate the cardioprotective potential of canagliflozin in isoprenaline (ISP)-induced cardiac fibrosis in a mouse model.
Materials and Methods:
Cardiac fibrosis was induced by the subcutaneous administration of ISP (20 mg/kg body weight) for 14 consecutive days. Canagliflozin (10 mg/kg body weight, intraperitoneally) was coadministered to evaluate its protective effects. Serum biochemical parameters, oxidative stress markers, and cardiac fibrosis-related gene expression were analyzed.
Results:
Canagliflozin coadministration significantly reduced the serum creatine kinase–myocardial band, triglyceride, and cholesterol levels compared to the ISP-only group. A marked decrease in tissue glucosamine level and lipid peroxidation, along with a significant increase in reduced glutathione, was observed. Catalase and superoxide dismutase levels showed mild improvement. Moreover, connective tissue growth factor gene expression was significantly downregulated in the canagliflozin-treated group.
Conclusion:
Canagliflozin attenuated the ISP-induced cardiac fibrosis by improving antioxidant status, modulating lipid metabolism, and downregulating profibrotic gene expression, suggesting its potential as a therapeutic agent against cardiac fibrosis.