title: Diallyl trisulfide attenuates carbon tetrachloride-caused liver injury and fibrogenesis and reduces hepatic oxidative stress in rats.
abstract: Liver fibrosis represents a frequent event following chronic insult to trigger wound healing reactions with accumulation of extracellular matrix (ECM) components in the liver. Activation of hepatic stellate cells (HSCs) is the pivotal event during liver fibrogenesis. The process of HSC activation is accompanied by enhanced expression of a series of marker proteins and pro-fibrogenic signal molecules. Natural products have been an important source of antifibrotic remedies. The present study aims to evaluate the in vivo effects of diallyl trisulfide (DATS), the primary component derived from garlic, on carbon tetrachloride (CCl4)-induced injury and fibrosis in rats. Our results showed that DATS improved liver histological architecture and decreased hepatic enzyme levels, but did not significantly affect cytochrome P450 2E1 activity in vivo. DATS also attenuated collagen deposition and inhibited HSC activation in the rat fibrotic liver demonstrated by reduced expression of α-smooth muscle actin, α1(I) procollagen, and fibronectin-three key markers of HSC activation-and by downregulation of transforming growth factor-β receptor 1, platelet-derived growth factor-β receptor, and epidermal growth factor receptor-three key receptors transmitting pro-fibrogenic pathways. In addition, DATS ameliorated hepatic oxidative stress by diminishing the levels of lipid peroxides and malondialdehyde and enhancing glutathione content. These data collectively revealed that DATS protected the rat liver from CCl4-caused injury and fibrogenesis in vivo, which was associated with inhibition of HSC activation and attenuation of oxidative stress. Our results suggested DATS as a promising antifibrogenic candidate for the prevention and treatment of liver fibrosis.
authors.affiliation: Department of Pharmacology, College of Pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing, 210023, Jiangsu, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Zhu
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Liang
authors.initials: L
authors.lastname: Zhou
authors.forename: Desong
authors.initials: D
authors.lastname: Kong
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Yin
authors.initials: Y
authors.lastname: Lu
authors.forename: Shizhong
authors.initials: S
authors.lastname: Zheng
mesh_terms: D000498:Allyl Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D003094:Collagen / Q000235:genetics; D055166:Hepatic Stellate Cells / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013440:Sulfides / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000498:Allyl Compounds; D013440:Sulfides; C042577:diallyl trisulfide; D003094:Collagen; D002251:Carbon Tetrachloride