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Tetramethylpyrazine prevents ethanol-induced hepatocyte injury via activation of nuclear factor erythroid 2-related factor 2.
- Source :
-
Life Sciences . Nov2015, Vol. 141, p119-127. 9p. - Publication Year :
- 2015
-
Abstract
- Aims Inhibiting the major features of alcoholic liver disease (ALD) such as lipid accumulation and oxidative stress is a promising strategy of treating ALD. Tetramethylpyrazine (TMP) has curative effects on various diseases. However, the effects of TMP on ethanol-induced hepatocyte injury and the related mechanisms remain unclear. The aim of this study is to elucidate the effects of TMP and the potential mechanisms in vitro. Main methods Ethanol-stimulated LO2 cells were used as an in vitro model of ALD. Several biomarkers related to cell injury, lipid accumulation, and oxidative stress were determined to evaluate the effects of TMP. Nuclear factor erythroid 2-related factor 2 (Nrf2) expression plasmids and Nrf2 small interfering RNA (siRNA) were used to establish the role of Nrf2. Key findings TMP increased Nrf2 expression and nuclear translocation. TMP prevented ethanol-induced hepatocyte injury, as indicated by the enhanced cell viability, reduced activities of aspartate transaminase and alanine aminotransferase in the culture medium, and inhibition of cell apoptosis. Furthermore, TMP reduced the levels of lipid droplets, triglyceride, and total cholesterol, probably by regulating genes related to lipid metabolism. Besides, TMP alleviated ethanol-induced oxidative stress by increasing superoxide dismutase activity and the glutathione level and by reducing the levels of reactive oxygen species and malondialdehyde. In addition, overexpression of Nrf2 enhanced the effects of TMP on cell injury, lipid accumulation, and oxidative stress, whereas Nrf2 siRNA eliminated the effects of TMP. Significance TMP prevents ethanol-induced hepatocyte injury by inhibiting lipid accumulation and oxidative stress, and via an Nrf2 activation-dependent mechanism. [ABSTRACT FROM AUTHOR]
- Subjects :
- *PYRAZINES
*NF-kappa B
*ETHANOL
*LIPID analysis
*LIVER cells
*OXIDATIVE stress
Subjects
Details
- Language :
- English
- ISSN :
- 00243205
- Volume :
- 141
- Database :
- Academic Search Index
- Journal :
- Life Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 110944281
- Full Text :
- https://doi.org/10.1016/j.lfs.2015.08.018