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.
Highlights
Diabetic nephropathy is characterized by initial oxidative stress, inflammatory response, thickening of basement membranes, expansion of mesangial matrix and interstitial fibrosis, podocytes and renal cell death, increased albuminuria, and renal dysfunction [1,2,3]
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
We demonstrate that after multiple low-dose streptozotocin (MLD-STZ) induction of diabetes, blood glucose levels in diabetes (DM) groups with or without SFN treatment were significantly increased without difference between DM and DM plus SFN (DM/SFN) group (Table 1)
Summary
Diabetic nephropathy is characterized by initial oxidative stress, inflammatory response, thickening of basement membranes, expansion of mesangial matrix and interstitial fibrosis, podocytes and renal cell death, increased albuminuria, and renal dysfunction [1,2,3]. Upon exposure of cells to Oxidative Medicine and Cellular Longevity oxidative stress or electrophilic compounds, Nrf dissociates from KEAP1 and translocates into the nucleus to bind to antioxidant-responsive elements in the genes encoding antioxidant enzymes, namely, NADPH quinone oxidoreductase (NQO1), heme oxygenase-1 (HO-1), glutathione Stransferase, superoxide dismutase (SOD), catalase (CAT), and γ-glutamylcysteine synthetase. Upregulation of these Nrf2-dependent antioxidants promotes detoxification, and anti-inflammatory function [6, 7]. A growing body of evidence has indicated a critical role for activator-induced Nrf upregulation in the prevention of diabetic complications, including nephropathy [7, 8]
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