Green Tea Polyphenols Alleviate Hydrogen Peroxide-Induced Oxidative Stress, Inflammation, and Apoptosis in Bovine Mammary Epithelial Cells by Activating ERK1/2–NFE2L2–HMOX1 Pathways

Abstract

Oxidative stress (OS) is one of the main limiting factors affecting the length of lactation and milk quality in dairy cows. For high-producing dairy cows, the OS of mammary glands is a serious problem. Green tea polyphenols (GTP), found mainly in tea, are a combination of many phenols. GTP have a good effect on antioxidation, inflammation resistance, obesity, fat cell metabolism improvement, and lowering of blood lipid. Therefore, we studied the role of GTP on OS in dairy cows and further investigated whether GTP alleviates oxidative damage of bovine mammary epithelial cells (BMECs) induced by hydrogen peroxide (H2O2) and its underlying molecular mechanism. In this study, 500 μM of H2O2 for 12 h incubation was chosen as the condition of the OS model of BMECs. In addition, the present results found that treatment with GTP alleviated the oxidative damage induced by H2O2 [the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) were significantly increased, and the contents of malondialdehyde (MDA), 8-isoprostaglandin (8-iso-PG), 8-oxo-deoxyguanosine (8-OHdG), and protein carbonyl (PC) and caspase-3 and caspase-9 activities were significantly reduced]. These effects are related to the activation of the erythrocyte-derived nuclear factor 2-like protein 2 (NFE2L2) signaling pathway and the inactivation of the caspase/Bcl-2 apoptotic pathway. When NFE2L2 short interfering RNA (siRNA) was used to downregulate the expression of NFE2L2 in cultured BMECs, NFE2L2-siRNA transfection abolished the protective effect of GTP on H2O2-induced intracellular reactive oxygen species (ROS) accumulation and apoptosis. In addition, the mitogen-activated protein kinase (MAPK) inhibition test further proved that GTP relieved H2O2-induced oxidative damage by activating the NFE2L2 signaling pathway, which was achieved by activating the extracellular-regulated kinase 1/2 (ERK1/2) signaling pathway. Overall, the results indicate that GTP has a beneficial effect on the redox balance of BMECs. In addition, GTP might be a latent antioxidant in vivo, which can be administered to ruminants during stressful periods such as the perinatal period.

Effects of PUFA-Rich Dietary Strategies on Ruminants’ Mammary Gland Gene Network: A Nutrigenomics Review

“…According to the accessed literature, plant compounds; AAs, such as methionine (Met) [ 93 ]; trace minerals and vitamins [ 79 , 94 ]; and plant bioactive compounds [ 95 ] seem to efficiently contribute to lessening the burden of oxidative stress ( Table 3 ). Aside from that, the impaired antioxidant status can cause severe damage to the immune system; thus, nutrition research also targets the mechanisms regulating gene expression on the immune system, as has been shown by several studies that will be presented in the following section.…”

“…In several experiments with the use of polyphenols, some promising results have been published. For instance, the treatment of bovine MECs with tea polyphenols (100 μg/mL) enhanced the protein abundance of NFE2L2 and HMOX1 [ 95 ]. Thoroughly, the co-treatment of cells with tea polyphenols and H 2 O 2 increased the mRNA abundance of NFE2L2 , HMOX1 , and NQO1 compared to H 2 O 2 treatment.…”

“…Thoroughly, the co-treatment of cells with tea polyphenols and H 2 O 2 increased the mRNA abundance of NFE2L2 , HMOX1 , and NQO1 compared to H 2 O 2 treatment. In the same manner, the co-treatment of cells with tea-polyphenols and H 2 O 2 caused an upsurge in BCL2 , but it significantly diminished BAX , CASPASE3 , and CASPASE9 mRNA abundance compared with the H 2 O 2 treatment [ 95 ]. In the same experiment, the mRNA expression of TNFA , IL6 , and IL1B , was decreased in the tea-polyphenols plus H 2 O 2 -treated group compared with the H 2 O 2 -treated group, along with a reduced apoptosis rate [ 95 ].…”

“…In the same manner, the co-treatment of cells with tea-polyphenols and H 2 O 2 caused an upsurge in BCL2 , but it significantly diminished BAX , CASPASE3 , and CASPASE9 mRNA abundance compared with the H 2 O 2 treatment [ 95 ]. In the same experiment, the mRNA expression of TNFA , IL6 , and IL1B , was decreased in the tea-polyphenols plus H 2 O 2 -treated group compared with the H 2 O 2 -treated group, along with a reduced apoptosis rate [ 95 ]. Therefore, Ma et al [ 95 ] concluded that tea-polyphenols may effectively set up a favorable antioxidant by inhibiting the activation of CASPASE3 and the expression of BAX and by strengthening the mRNA expression of BCL2 .…”

“…In the same experiment, the mRNA expression of TNFA , IL6 , and IL1B , was decreased in the tea-polyphenols plus H 2 O 2 -treated group compared with the H 2 O 2 -treated group, along with a reduced apoptosis rate [ 95 ]. Therefore, Ma et al [ 95 ] concluded that tea-polyphenols may effectively set up a favorable antioxidant by inhibiting the activation of CASPASE3 and the expression of BAX and by strengthening the mRNA expression of BCL2 . In addition, tea-polyphenols can lessen the inflammatory burden caused by ROS by inhibiting the expression of inflammatory cytokines.…”