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Biochim Biophys Acta. 2013 Oct;1830(10):4848-59. doi: 10.1016/j.bbagen.2013.06.028. Epub 2013 Jun 28.

The activation of HO-1/Nrf-2 contributes to the protective effects of diallyl disulfide (DADS) against ethanol-induced oxidative stress.

Author information

1
School of Public Health, Shandong University, Shandong Province, Jinan City, People's Republic of China. zengtao@sdu.edu.cn

Abstract

BACKGROUND:

Diallyl disulfide (DADS) is a garlic-derived organosulfur compound. The current study is designed to evaluate the protective effects of DADS against ethanol-induced oxidative stress, and to explore the underlying mechanisms by examining the HO-1/Nrf-2 pathway.

METHODS:

We investigated whether or not DADS could activate the HO-1 in normal human liver cell LO2, and then evaluated the protective effects of DADS against ethanol-induced damage in LO2 cells and in acute ethanol-intoxicated mice. The biochemical parameters were measured using commercial kits. HO-1 mRNA level was determined by RT-PCR. Histopathology and immunofluorescence assay were performed with routine methods. Protein levels were measured by western blot.

RESULTS:

DADS significantly increased the mRNA and protein levels of HO-1, stimulated the nuclear translocation of Nrf-2 and increased the phosphorylation of MAPK in LO2 cells. The nuclear translocation of Nrf-2 was abrogated by MAPK inhibitors. DADS significantly suppressed ethanol-induced elevation of lactate dehydrogenase (LDH) and aspartate transaminase (AST) activities, decrease of glutathione (GSH) level, increase of malondialdehyde (MDA) levels, and apoptosis of LO2 cells, which were all blocked by ZnPPIX. In mice, DADS effectively suppressed acute ethanol-induced elevation of aminotransferase activities, and improved liver histopathological changes, which might be associated with HO-1 activation.

CONCLUSION:

These results demonstrate that DADS could induce the activation of HO-1/Nrf-2 pathway, which may contribute to the protective effects of DADS against ethanol-induced liver injury.

GENERAL SIGNIFICANCE:

DADS may be beneficial for the prevention and treatment of ALD due to significant activation of HO-1/Nrf-2 pathway.

KEYWORDS:

ALD; ALT; AST; Alcoholic liver disease; DADS; Diallyl disulfide; ERK; GSH; HO-1; JNK; LDH; MAPK; MDA; NF-E2 related factor-2; Nrf-2; Oxidative stress; PI3K; PKA; PKC; ROS; SOD; ZnPPIX; alanine aminotransferase; alcoholic liver disease; aspartate transaminase; c-Jun N-terminal kinase; diallyl disulfide; extracellular signal-regulated protein kinases; glutathione; heme oxygenase 1; lactate dehydrogenase; malondialdehyde; mitogen-activated protein kinase; phosphatidyl inositol 3-kinase; protein kinase A; protein kinase C; reactive oxygen species; superoxide dismutase; zinc protoporphyrin-IX

PMID:
23816986
DOI:
10.1016/j.bbagen.2013.06.028
[Indexed for MEDLINE]

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