Theaflavins attenuate ethanol‑induced oxidative stress and cell apoptosis in gastric mucosa epithelial cells via downregulation of the mitogen‑activated protein kinase pathway

Wang,Zheng; Luo,Hesheng; Xia,Hong

doi:10.3892/mmr.2018.9352

Theaflavins attenuate ethanol‑induced oxidative stress and cell apoptosis in gastric mucosa epithelial cells via downregulation of the mitogen‑activated protein kinase pathway

Authors:
- Zheng Wang
- Hesheng Luo
- Hong Xia
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Affiliations: Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
Published online on: August 3, 2018 https://doi.org/10.3892/mmr.2018.9352
Pages: 3791-3799
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Ethanol‑induced diseases of the gastric mucosa are the most common and refractory diseases of gastrointestinal system in clinic, and are mediated by oxidative stress and apoptosis pathways. Theaflavins (TFs) are considered to be antioxidants. The present study aimed to determine the molecular mechanism underlying the ability of TFs to attenuate ethanol‑induced oxidative stress and apoptosis in GES‑1 gastric mucosa epithelial cells. A Cell Counting Kit‑8 (CCK‑8) assay was performed to investigate the cell viability of GES‑1 cells following administration of ethanol (0.5 mol/l) and subsequent treatment with TFs (20, 40 and 80 µg/ml) for specific time intervals. A carboxyfluorescein diacetate succinimidyl ester assay was used to measure proliferation and further investigate the results of the CCK‑8 assay. Flow cytometry was performed to measure reactive oxygen species (ROS) levels and the apoptosis rates of GES‑1 cells. Furthermore, levels of oxidative stress‑associated factors, including malondialdehyde, superoxide dismutase and glutathione, were investigated using commercial kits. Reverse transcription‑quantitative polymerase chain reaction and western blot assays were performed to determine the expression levels of apoptosis‑associated factors, as well as the phosphorylation levels of extracellular signal‑regulated kinase (ERK), c‑Jun N‑terminal kinase (JNK) and p38 kinase (p38). The results of the present study demonstrated that treatment with ethanol inhibited GES‑1 cell proliferation, and enhanced ROS levels and apoptosis rates, potentially via downregulation of B‑cell lymphoma‑2 (Bcl‑2) expression and upregulation of Bcl‑2‑associated X and caspase‑3 expression levels, as well as enhancing the phosphorylation levels of ERK, JNK and p38. However, treatment with TFs was revealed to attenuate the effects of ethanol administration on GES‑1 cells in a dose‑dependent manner. In conclusion, TFs may attenuate ethanol‑induced oxidative stress and apoptosis in gastric mucosa epithelial cells via downregulation of various mitogen‑activated protein kinase pathways.

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