title: Therapeutic sesamol attenuates monocrotaline-induced sinusoidal obstruction syndrome in rats by inhibiting matrix metalloproteinase-9.
abstract: We investigated the therapeutic effect of sesamol against monocrotaline-induced sinusoidal obstruction syndrome (SOS) in rats. Male Sprague-Dawley rats were gavaged with a single dose of monocrotaline (90 mg/kg) to induce SOS. Sesamol (5, 10, 20, and 40 mg/kg) was subcutaneously injected 24 h after monocrotaline treatment. Control rats were given saline only. Aspartate transaminase, alanine transaminase, mast cells, CD 68(+) Kupffer cells, neutrophils, myeloperoxidase, matrix metalloproteinase-9 (MMP-9), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), laminin, and collagen were assessed 48 h after monocrotaline treatment. All tested parameters, except for TIMP-1, laminin, and collagen, were significantly higher in monocrotaline-treated rats than in control rats, and, except for TIMP-1, laminin, and collagen, significantly lower in sesamol-treated rats than in monocrotaline-treated rats. In addition, liver pathology revealed that sesamol offered significant protection against SOS. We conclude that a single dose of sesamol therapeutically attenuated SOS by decreasing the recruitment of inflammatory cells, downregulating MMP-9, and upregulating TIMP-1 expression.
authors.affiliation: Department of Environmental and Occupational Health, National Cheng Kung University Medical College, Tainan, Taiwan.
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Periasamy
authors.forename: Dur-Zong
authors.initials: DZ
authors.lastname: Hsu
authors.forename: Shin-Yi
authors.initials: SY
authors.lastname: Chen
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Yang
authors.forename: Victor Raj Mohan
authors.initials: VR
authors.lastname: Chandrasekaran
authors.forename: Ming-Yie
authors.initials: MY
authors.lastname: Liu
mesh_terms: D000818:Animals; D052117:Benzodioxoles / Q000494:pharmacology* / Q000627:therapeutic use; D003094:Collagen / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D006504:Hepatic Veno-Occlusive Disease / Q000139:chemically induced* / Q000188:drug therapy / Q000201:enzymology* / Q000276:immunology; D007728:Kupffer Cells / Q000187:drug effects / Q000276:immunology; D007797:Laminin / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000293:injuries / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology; D061965:Matrix Metalloproteinase Inhibitors; D016686:Monocrotaline / Q000009:adverse effects*; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D009195:Peroxidase / Q000037:antagonists & inhibitors; D010636:Phenols / Q000494:pharmacology* / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D052117:Benzodioxoles; D007797:Laminin; D061965:Matrix Metalloproteinase Inhibitors; D010636:Phenols; D011480:Protease Inhibitors; D019715:Tissue Inhibitor of Metalloproteinase-1; D016686:Monocrotaline; D003094:Collagen; C025583:sesamol; D009195:Peroxidase