Prevention of Diabetic Nephropathy by Sulforaphane: Possible Role of Nrf2 Upregulation and Activation

Abstract

The present study was to investigate whether sulforaphane (SFN) can prevent diabetic nephropathy in type 1 diabetic mouse model induced by multiple low-dose streptozotocin. Diabetic and age-matched control mice were given SFN at 0.5 mg/kg body weight daily for 3 months. At the end of 3-month SFN treatment, the diabetic nephropathy, shown by renal inflammation, oxidative damage, fibrosis, and dysfunction, was significantly prevented along with an elevation of renal Nrf2 expression and transcription in diabetes/SFN group compared with diabetic group. However, this renal prevention by SFN was not seen when the 3-month SFN-treated diabetic mice were aged for additional 3 months without further SFN treatment. Nrf2-mediated renal protective effects in diabetes were evaluated in human renal tubular HK11 cells transfected with control and Nrf2 siRNA and treated with 27.5 mM mannitol or high glucose plus palmitate (300 μM). Blockade of Nrf2 expression completely abolished SFN prevention of the profibrotic effect induced by high glucose plus palmitate. These results support that renal Nrf2 expression and its transcription play important roles in SFN prevention of diabetes-induced renal damage. However, the SFN preventive effect on diabetes-induced renal pathogeneses is not sustained, suggesting the requirement of continual use of SFN for its sustained effect.

The role of DJ-1/Nrf2 pathway in the pathogenesis of diabetic nephropathy in rats

“…10 And Nrf2 plays a central role in the protective effect against oxidative and apoptosis damage in DN. 11,12 Hence, it was of interest to investigate the role and the proper time nodes of DJ-1/Nrf2 pathway in the pathogenesis of DN in rats.…”

Dysregulation of Nrf2 Signaling in Diabetes: An Opportunity for a Multitarget Approach

“…SFN has been shown to have similar effects in diabetic nephropathy. 3 months of SFN treatment attenuated loss of kidney function, fibrosis and TGF-β expression, reduced inflammation and TNFα, and oxidative stress in the kidneys of diabetic mice [47,48] [49].…”

The Effect of Nrf2 on Diabetic Complications

“…Under physiological conditions Kelch-like ECH-associated protein 1 (Keap1) binds to Nrf2 and sequesters it in the cytoplasm. Under basal conditions, Keap1 mediates rapid ubiquitination and subsequent degradation of Nrf2 by the proteasome [7,35,36,38]. Studies have demonstrated the beneicial role of Nrf2 induction in the prevention of DN [37].…”

“…Upregulation of these Nrf2-dependent antioxidants promotes detoxiication and anti-inlammatory function. A growing body of evidence has indicated a critical role for activator-induced Nrf2 upregulation in the prevention of diabetic complications, including DN [36].…”