Sulforaphane reduction of testicular apoptotic cell death in diabetic mice is associated with the upregulation of Nrf2 expression and function

Abstract

L. Sulforaphane reduction of testicular apoptotic cell death in diabetic mice is associated with the upregulation of Nrf2 expression and function. Am J Physiol Endocrinol Metab 307: E14 -E23, 2014. First published May 6, 2014 doi:10.1152/ajpendo.00702.2013.-Diabetes-induced testicular cell death is due predominantly to oxidative stress. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is an important transcription factor in controlling the antioxidative system and is inducible by sulforaphane (SFN). To test whether SFN prevents diabetes-induced testicular cell death, an insulin-defective stage of type 2 diabetes (IDS-T2DM) was induced in mice. This was accomplished by feeding them a high-fat diet (HFD) for 3 mo to induce insulin resistance and then giving one intraperitoneal injection of streptozotocin to induce hyperglycemia while age-matched control mice were fed a normal diet (ND). IDS-T2DM and ND-fed control mice were then further subdivided into those with or without 4-mo SFN treatment. IDS-T2DM induced significant increases in testicular cell death presumably through receptor and mitochondrial pathways, shown by increased ratio of Bax/Bcl2 expression and cleavage of caspase-3 and caspase-8 without significant change of endoplasmic reticulum stress. Diabetes also significantly increased testicular oxidative damage and inflammation. All of these diabetic effects were significantly prevented by SFN treatment with upregulated Nrf2 expression. These results suggest that IDS-T2DM induces testicular cell death presumably through caspase-8 activation and mitochondria-mediated cell death pathways and also by significantly downregulating testicular Nrf2 expression and function. SFN upregulates testicular Nrf2 expression and its target antioxidant expression, which was associated with significant protection of the testis from IDS-T2DM-induced germ cell death. male germ cell death; sulforaphane; nuclear factor (erythroid-derived 2)-like 2; type 2 diabetes; high-fat diet

Sulforaphane Treatment of Stress Urinary Incontinence Via the Nrf2-ARE Pathway in a Rat Model

“…This result indicated that SFN could protect the urinary function of rats in an effective manner. Furthermore, daily intraperitoneal injections of SFN (0.5 mg/kg) have previously been demonstrated as effective [35]. The urodynamic outcome was consistent with the histological changes in the urethral sphincter.…”

Evaluation of the Fas/FasL signaling pathway in diabetic rat testis

“…We found that increased activation of caspase 8 is correlated with germ cell apoptosis in diabetic animals. Similarly, Wang et al (2014) Downloaded by [University of California, San Diego] at 18:07 10 March 2016…”

Natural Nrf2 activators in diabetes

“…C57BL/6J mice treated with HFD (60% fat). After three SFN preserved the normal Nrf2 expression and SFN increased HO-1 and NQO1 expression and decreased 4- [94] A C C E P T E D M A N U S C R I P T…”

“…In these studies [78][79][80][81], Nrf2 activation increased antioxidant protein expression and was protective effect against cell death. hyperglycemic-induced damage in brain [93] and testis [94]. These natural Nrf2 activators may be clustered in four groups.…”