Prevention of diabetic nephropathy by sulforaphane: possible role of Nrf2 upregulation and activation.
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.
Department of Nephrology, The Second Hospital Jilin University, Changchun 130041, China.
Wenpeng
W
Cui
Yang
Y
Bai
Xiao
X
Miao
Ping
P
Luo
Qiang
Q
Chen
Yi
Y
Tan
Madhavi J
MJ
Rane
Lining
L
Miao
Lu
L
Cai
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D002460:Cell Line; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism / Q000473:pathology; D003928:Diabetic Nephropathies / Q000209:etiology / Q000517:prevention & control*; D004195:Disease Models, Animal; D005947:Glucose / Q000494:pharmacology; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D017879:Isothiocyanates; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D051379:Mice; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010168:Palmitates / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D013454:Sulfoxides; D013482:Superoxide Dismutase / Q000378:metabolism; D013861:Thiocyanates / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects*
D016588:Anticarcinogenic Agents; D017879:Isothiocyanates; D051267:NF-E2-Related Factor 2; D010168:Palmitates; D034741:RNA, Small Interfering; D013454:Sulfoxides; D013861:Thiocyanates; D008353:Mannitol; D002374:Catalase; D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase; D016660:NAD(P)H Dehydrogenase (Quinone); C016766:sulforaphane; D005947:Glucose