Protective Mechanism of Sulforaphane on Cadmium-Induced Sertoli Cell Injury in Mice Testis via Nrf2/ARE Signaling Pathway

Abstract

The present study evaluated the mechanism underlying the protective effect of sulforaphane (SFN) on cadmium (Cd)-induced Sertoli cell (TM4 cells) injury in mice. The apoptosis rate of cells in each group was detected by flow cytometry. It was determined the effect of SFN on the expression of downstream molecular targets of Nrf2/ARE axis and on the lipid peroxide content. The related genes involved in the nuclear factor E2-related factor 2(Nrf2)/antioxidant response element (ARE) signaling pathway were evaluated by RT-PCR; for example, the mRNA expression levels of Nrf2, heme oxygenase-1 (HO-1), glutathione peroxidase (GSH-Px), quinone oxidoreductase 1 (NQO1), and γ-glutamylcysteine synthetase (γ-GCS), while the protein expression levels were assessed by Western blot. Our results showed that the mRNA and protein expression levels of Nrf2, HO-1, NQO1, GSH-Px, and γ-GCS were increased in various degree when the Sertoli cells were to added different concentrations of SFN. Our results also showed that SFN reduced the apoptosis rate, increased the activity of T-SOD, inhibited the increase of the MDA content caused by Cd. Meanwhile, SFN could increase the mRNA and protein expression levels of Nrf2, HO-1 and NQO1 and reduced the mRNA and protein expression levels of GSH-Px and γ-GCS caused by Cd in Sertoli cells (p < 0.01). Taken together, SFN could improve the antioxidant capacity of Sertoli cells, and exert a protective effect on the oxidative damage and apoptosis of Cd-induced Sertoli cells through the activation of Nrf2/ARE signal transduction pathway.

Dexmedetomidine Attenuates Neuroinflammatory–Induced Apoptosis after Traumatic Brain Injury via Nrf2 signaling pathway

“…Nrf2 is an important protective protein and plays a key role in cells adapting to oxidative stress by elevating phase α enzymes, such as NQO1 and HO‐1, which are activated after TBI . Noxious stimulation can increase Nrf2 expression and its translocation into the nucleus to bind with antioxidant response‐element sequences . To confirm that the Nrf2 signaling pathway is involved in the neuroprotection by DEX, Nrf2 protein expression in the brain tissue of rats with TBI was assessed after administering DEX.…”

The developmental basis of disease: Update on environmental exposures and animal models

“…Indeed, individuals consuming a healthful diet already have a lower risk of chronic inflammatory disease and thus may be less susceptible to environmental insults . Indeed, a diet high in broccoli, kale, collard and/or brussel sprouts contains chemicals that on hydrolysis release sulforaphane which protects against oxidative stress via activation of the Nrf2 pathway in some tissues . Sulforaphane also induces glutathione S‐transferases which leads to increased excretion of glutathione‐derived conjugates of benzene and acrolein .…”

“…53 Indeed, a diet high in broccoli, kale, collard and/or brussel sprouts contains chemicals that on hydrolysis release sulforaphane which protects against oxidative stress via activation of the Nrf2 pathway in some tissues. 54,55 Sulforaphane also induces glutathione S-transferases which leads to increased excretion of glutathionederived conjugates of benzene and acrolein. 56 An interesting example involves the use of a broccoli sprout beverage to detoxify airborne pollutants.…”

Measuring Sulforaphane and Its Metabolites in Human Plasma: A High Throughput Method

“…Sulforaphane is further metabolized into a number of other active metabolites (Figure 1). Sulforaphane and its metabolites are gene transcription activators that release bound nuclear factor erythroid factor 2 (NFE2L2) in the cell cytosol, allowing its nuclear translocation [13,[18][19][20][21]. In the nucleus, NFE2L2 induces transcription of a cassette of cellular "safeguarding" genes in the antioxidant response element (ARE) of cellular DNA [22].…”