Sulforaphane protects granulosa cells against oxidative stress via activation of NRF2-ARE pathway

Abstract

Sulforaphane (SFN) has been considered as an indirect antioxidant and potential inducer of the Nrf2-ARE pathway. This study was conducted to investigate the protective role of SFN against oxidative stress in bovine granulosa cells (GCs). GCs were collected from antral follicles (4-8 mm) and cultured according to the experimental design where group 1 = control, group 2 = treated with SFN, group 3 = treated with hydrogen peroxide (HO), group 4 = pretreated with SFN and then with HO (protective) and group 5 = treated with HO followed by SFN treatment (rescuing). Results showed that SFN pretreatment significantly increases cell viability and reduces cytotoxicity in GCs under oxidative stress. Following HO exposure, expression of NRF2 was found to be significantly increased (p < 0.05) in SFN-pretreated cells, while no significant differences were observed between group 3 and group 5, although the expression was significantly increased compared to the control group. Moreover, the relative abundance of the NRF2 downstream target antioxidant genes (CAT, PRDX1, SOD1 and TXN1) were higher (fold change ranged from 7 to 14, p < 0.05) in sulforaphane pretreated GCs. Low level of ROS and lipid accumulation and higher mitochondrial activity were observed in GCs pretreated with SFN, whereas no such changes were observed in GCs treated with SFN after exposure to oxidative stress (group 5). Thus, we suggest that SFN pretreatment effectively protects GCs against oxidative damage through the activation of the NRF2-ARE pathway, whereas addition of SFN during oxidative insult failed to rescue GCs.

Quercetin alleviated H2O2‐induced apoptosis and steroidogenic impairment in goat luteinized granulosa cells

“…[ 32,33 ] In our research, we found that incubation with 250 µM H 2 O 2 for 24 hours could induce apoptosis of goat LGCs, which was consistent with the reports on mice, porcine, and bovine GCs. [ 6,34,35 ] The mRNA expressions of Nrf2 and its downstream antioxidative genes increased in the H 2 O 2 group, which is similar to the studies on neural stem cells [ 36 ] and bovine GCs. [ 19,35 ] Nevertheless, some studies showed that treatment with H 2 O 2 did not impair the expression of Nrf2 .…”

“…[ 6,34,35 ] The mRNA expressions of Nrf2 and its downstream antioxidative genes increased in the H 2 O 2 group, which is similar to the studies on neural stem cells [ 36 ] and bovine GCs. [ 19,35 ] Nevertheless, some studies showed that treatment with H 2 O 2 did not impair the expression of Nrf2 . [ 19,33 ] This may be due to the different concentrations of H 2 O 2 , action time, culture medium, cell types, or animal species.…”

<p>Protective Effect of Pravastatin on Myocardial Ischemia Reperfusion Injury by Regulation of the miR-93/Nrf2/ARE Signal Pathway</p>

“…It is often combined with the upstream promoter region of the downstream regulatory antioxidant genes (such as HO-1, NQO1, SOD, GPX), and the polymer combined in the tissue can induce the up-regulation of the expression of endogenous cell antioxidant protection genes in the organism, so as to maintain the cells in the oxidation and antioxidant water in a state of equilibrium. 17,19,22 Many research have proved that the generation of a large number of oxygen free radicals in myocardial cells, the changes of cell adhesion molecules, the overload of calcium ions, the dysfunction of myocardial energy metabolism, and the occurrence of apoptosis are all correlated with myocardial I/R injury. The correlation between these mechanisms constituted a complex signal network, which restricts and balances each other.…”

“…It is often combined with the upstream promoter region of the downstream regulatory antioxidant genes (such as HO-1, NQO1, SOD, GPX), and the polymer combined in the tissue can induce the up-regulation of the expression of endogenous cell antioxidant protection genes in the organism, so as to maintain the cells in the oxidation and antioxidant water in a state of equilibrium. 17 , 19 , 22 …”

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

“…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.…”