Diallyl trisulfide protects against ethanol-induced oxidative stress and apoptosis via a hydrogen sulfide-mediated mechanism.
Garlic is one natural source of organic sulfur containing compounds and has shown promise in the treatment of chronic liver disease. Dietary garlic consumption is inversely correlated with the progression of alcoholic fatty liver (AFL), although the exact underlying mechanisms are not clear. Our previous studies also have shown that diallyl trisulfide (DATS), the primary organosulfur compound from Allium sativum L, displayed anti-lipid deposition and antioxidant properties in AFL. The aim of the present study was to clarify the underlying mechanisms. In the present study, we used the intragastric infusion model of alcohol administration and human normal liver cell line LO2 cultured with suitable ethanol to mimic the pathological condition of AFL. We showed that accumulation of intracellular reactive oxygen species (ROS) was lowered significantly by the administration of DATS, but antioxidant capacity was increased by DATS. Additionally, DATS inhibited hepatocyte apoptosis via down-regulating Bax expression and up-regulating Bcl-2 expression, and attenuated alcohol-induced caspase-dependent apoptosis. More importantly, using iodoacetamide (IAM) to block hydrogen sulfide (H2S) production from DATS, we noted that IAM abolished all the above effects of DATS in ethanol-treated LO2 cells. Lastly, we found DATS could increase the expressions of cystathionine gamma-lyase (CSE) and cystathionine beta-synthase (CBS), the major H2S-producing enzymes. These results demonstrate that DATS protect against alcohol-induced fatty liver via a H2S-mediated mechanism. Therefore, targeting H2S may play a therapeutic role for AFL.
Department of Pharmacy, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; National First-Class Key Discipline for Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Lian-Yun
LY
Chen
Department of Pharmacy, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; National First-Class Key Discipline for Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Qin
Q
Chen
Department of Pharmacy, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; National First-Class Key Discipline for Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Xiao-Jing
XJ
Zhu
Department of Pharmacy, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; National First-Class Key Discipline for Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
De-Song
DS
Kong
Department of Pharmacy, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; National First-Class Key Discipline for Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Li
L
Wu
Department of Pharmacy, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; National First-Class Key Discipline for Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Jiang-Juan
JJ
Shao
Department of Pharmacy, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; National First-Class Key Discipline for Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Material Medical, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: nytws@163.com.
Shi-Zhong
SZ
Zheng
D000498:Allyl Compounds / Q000627:therapeutic use*; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D000431:Ethanol; D005235:Fatty Liver, Alcoholic / Q000188:drug therapy*; D005737:Garlic / Q000276:immunology*; D022781:Hepatocytes / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013440:Sulfides / Q000627:therapeutic use*; D013447:Sulfites / Q000378:metabolism
D000498:Allyl Compounds; D000975:Antioxidants; D017382:Reactive Oxygen Species; D013440:Sulfides; D013447:Sulfites; C042577:diallyl trisulfide; D000431:Ethanol; C042345:hydrogen sulfite
Alcoholic fatty liver; Apoptosis; Diallyl trisulfide; Hydrogen sulfide; Oxidative stress