Journal of Biology and Today's World

Mitigation of Renal Fibrosis in Diabetic Mice by using Dapagliflozin Medication

Damien Rachel^{* *}Correspondence: Damien Rachel, Department of Endocrinology, University of São Paulo, São Paulo, Brazil, Email:

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Description

Renal fibrosis is a common and serious complication of diabetes mellitus, characterized by the excessive accumulation of extracellular matrix proteins in the kidney, leading to progressive loss of renal function. Among various therapeutic approaches, targeting the Renin-Angiotensin- Aldosterone System (RAAS) has been a cornerstone in managing renal complications in diabetes. Dapagliflozin, a Sodium-Glucose Co-Transporter 2 (SGLT2) inhibitor primarily used for treating type 2 diabetes, has emerged as a potential therapeutic agent in mitigating renal fibrosis. This article explains regarding the mechanisms underlying the mitigation of renal fibrosis in diabetic mice through the administration of Dapagliflozin.

Dapagliflozin acts by inhibiting SGLT2 in the proximal tubules of the kidney, thereby promoting urinary glucose excretion and reducing hyperglycemia in diabetic individuals. Beyond its glycemic control benefits, recent studies have elucidated additional renoprotective effects of Dapagliflozin, including attenuation of renal fibrosis. In diabetic mice models, Dapagliflozin administration has been shown to mitigate renal fibrosis by suppressing the angiotensin II/TGFβ signaling pathway.

Angiotensin II and Transforming Growth Factor-Beta (TGFβ) are key mediators implicated in the pathogenesis of renal fibrosis. Angiotensin II promotes renal fibrosis through various mechanisms, including stimulation of TGFβ production, inflammation, and oxidative stress. TGFβ, in turn, promotes the synthesis of extracellular matrix proteins and inhibits their degradation, leading to the development of fibrosis. Dapagliflozin intervenes in this process by inhibiting angiotensin II-induced TGFβ signaling, thereby mitigating renal fibrosis.

Several preclinical studies have provided compelling evidence supporting the efficacy of Dapagliflozin in attenuating renal fibrosis in diabetic mice. These studies have demonstrated that Dapagliflozin treatment reduces markers of renal fibrosis, such as collagen deposition, fibronectin expression, and α-smooth muscle actin levels. Moreover, histological analysis has revealed a decrease in tubulointerstitial fibrosis and glomerulosclerosis in Dapagliflozin-treated diabetic mice compared to untreated counterparts.

The findings from preclinical studies hold promising implications for clinical practice. Dapagliflozin, already approved for the management of type 2 diabetes, could potentially serve as a dual-purpose therapy for both glycemic control and renal protection in diabetic individuals at risk of developing renal complications. Clinical trials investigating the efficacy of Dapagliflozin in preventing or slowing the progression of diabetic kidney disease are underway, with preliminary results suggesting beneficial effects on renal outcomes.

While Dapagliflozin has shown promising renoprotective effects, it is essential to consider its safety profile and potential adverse effects. Common adverse effects associated with Dapagliflozin include genital mycotic infections, urinary tract infections, and volume depletion-related events such as hypotension and dehydration. Additionally, concerns have been raised regarding the risk of euglycemic diabetic ketoacidosis, particularly in individuals with type 1 diabetes or those with reduced insulin secretion.

In conclusion, Dapagliflozin emerges as a promising therapeutic agent for mitigating renal fibrosis in diabetic mice through its ability to suppress the angiotensin II/TGFβ signaling pathway. Beyond its primary role in glycemic control, Dapagliflozin offers additional renoprotective benefits, making it a potential candidate for the management of diabetic kidney disease. Further research, including clinical trials, is warranted to elucidate the long-term efficacy and safety of Dapagliflozin in preventing or delaying the progression of diabetic nephropathy in human subjects.