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Diallyl Trisulfide Suppresses Oxidative Stress-Induced Activation of Hepatic Stellate Cells through Production of Hydrogen Sulfide.
Oxid Med Cell Longev. 2017; 2017:1406726.OM

Abstract

Accumulating data reveal that garlic has beneficial effects against chronic liver disease. We previously reported that diallyl trisulfide (DATS), the primary organosulfur compound in garlic, reduced fibrosis and attenuated oxidative stress in rat fibrotic liver. The present study was aimed at elucidating the underlying mechanisms. The primary rat hepatic stellate cells (HSCs) were cultured and stimulated with hydrogen peroxide (H2O2) for inducing HSC activation under oxidative stress. We examined the effects of DATS on the profibrogenic properties and oxidative stress in H2O2-treated HSCs. The results showed that DATS suppressed and reduced fibrotic marker expression in HSCs. DATS arrested cell cycle at G2/M checkpoint associated with downregulating cyclin B1 and cyclin-dependent kinase 1, induced caspase-dependent apoptosis, and reduced migration in HSCs. Moreover, intracellular levels of reactive oxygen species and lipid peroxide were decreased by DATS, but intracellular levels of glutathione were increased in HSCs. Furthermore, DATS significantly elevated hydrogen sulfide (H2S) levels within HSCs, but iodoacetamide (IAM) reduced H2S levels and significantly abrogated DATS production of H2S within HSCs. IAM also abolished all the inhibitory effects of DATS on the profibrogenic properties and oxidative stress in HSCs. Altogether, we demonstrated an H2S-associated mechanism underlying DATS inhibition of profibrogenic properties and alleviation of oxidative stress in HSCs. Modulation of H2S production may represent a therapeutic remedy for liver fibrosis.

Authors+Show Affiliations

Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Key Laboratory of Therapeutic Material of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China; State Key Laboratory Cultivation Base for TCM Quality and Efficacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China.Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Key Laboratory of Therapeutic Material of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China; State Key Laboratory Cultivation Base for TCM Quality and Efficacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.Jiangsu Key Laboratory of Therapeutic Material of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China; State Key Laboratory Cultivation Base for TCM Quality and Efficacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China.Department of Pathology, School of Medicine, Saint Louis University, Saint Louis, MO 63104, USA.Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Key Laboratory of Therapeutic Material of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China; State Key Laboratory Cultivation Base for TCM Quality and Efficacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28303169

Citation

Zhang, Feng, et al. "Diallyl Trisulfide Suppresses Oxidative Stress-Induced Activation of Hepatic Stellate Cells Through Production of Hydrogen Sulfide." Oxidative Medicine and Cellular Longevity, vol. 2017, 2017, p. 1406726.
Zhang F, Jin H, Wu L, et al. Diallyl Trisulfide Suppresses Oxidative Stress-Induced Activation of Hepatic Stellate Cells through Production of Hydrogen Sulfide. Oxid Med Cell Longev. 2017;2017:1406726.
Zhang, F., Jin, H., Wu, L., Shao, J., Zhu, X., Chen, A., & Zheng, S. (2017). Diallyl Trisulfide Suppresses Oxidative Stress-Induced Activation of Hepatic Stellate Cells through Production of Hydrogen Sulfide. Oxidative Medicine and Cellular Longevity, 2017, 1406726. https://doi.org/10.1155/2017/1406726
Zhang F, et al. Diallyl Trisulfide Suppresses Oxidative Stress-Induced Activation of Hepatic Stellate Cells Through Production of Hydrogen Sulfide. Oxid Med Cell Longev. 2017;2017:1406726. PubMed PMID: 28303169.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Diallyl Trisulfide Suppresses Oxidative Stress-Induced Activation of Hepatic Stellate Cells through Production of Hydrogen Sulfide. AU - Zhang,Feng, AU - Jin,Huanhuan, AU - Wu,Li, AU - Shao,Jiangjuan, AU - Zhu,Xiaojing, AU - Chen,Anping, AU - Zheng,Shizhong, Y1 - 2017/02/20/ PY - 2016/07/31/received PY - 2016/12/22/revised PY - 2017/01/30/accepted PY - 2017/3/18/entrez PY - 2017/3/18/pubmed PY - 2017/3/28/medline SP - 1406726 EP - 1406726 JF - Oxidative medicine and cellular longevity JO - Oxid Med Cell Longev VL - 2017 N2 - Accumulating data reveal that garlic has beneficial effects against chronic liver disease. We previously reported that diallyl trisulfide (DATS), the primary organosulfur compound in garlic, reduced fibrosis and attenuated oxidative stress in rat fibrotic liver. The present study was aimed at elucidating the underlying mechanisms. The primary rat hepatic stellate cells (HSCs) were cultured and stimulated with hydrogen peroxide (H2O2) for inducing HSC activation under oxidative stress. We examined the effects of DATS on the profibrogenic properties and oxidative stress in H2O2-treated HSCs. The results showed that DATS suppressed and reduced fibrotic marker expression in HSCs. DATS arrested cell cycle at G2/M checkpoint associated with downregulating cyclin B1 and cyclin-dependent kinase 1, induced caspase-dependent apoptosis, and reduced migration in HSCs. Moreover, intracellular levels of reactive oxygen species and lipid peroxide were decreased by DATS, but intracellular levels of glutathione were increased in HSCs. Furthermore, DATS significantly elevated hydrogen sulfide (H2S) levels within HSCs, but iodoacetamide (IAM) reduced H2S levels and significantly abrogated DATS production of H2S within HSCs. IAM also abolished all the inhibitory effects of DATS on the profibrogenic properties and oxidative stress in HSCs. Altogether, we demonstrated an H2S-associated mechanism underlying DATS inhibition of profibrogenic properties and alleviation of oxidative stress in HSCs. Modulation of H2S production may represent a therapeutic remedy for liver fibrosis. SN - 1942-0994 UR - https://www.unboundmedicine.com/medline/citation/28303169/Diallyl_Trisulfide_Suppresses_Oxidative_Stress_Induced_Activation_of_Hepatic_Stellate_Cells_through_Production_of_Hydrogen_Sulfide_ L2 - https://dx.doi.org/10.1155/2017/1406726 DB - PRIME DP - Unbound Medicine ER -