Therapeutic Sesamol Attenuates Monocrotaline-Induced Sinusoidal Obstruction Syndrome in Rats by Inhibiting Matrix Metalloproteinase-9

• Published in: Cell biochemistry and biophysics Vol. 61; no. 2; pp. 327 - 336
• Main Authors: Periasamy, Srinivasan, Hsu, Dur-Zong, Chen, Shin-Yi, Yang, Shan-Shan, Chandrasekaran, Victor Raj Mohan, Liu, Ming-Yie
• Format: Journal Article
• Language: English
• Published: New York Humana Press Inc 01.11.2011; Springer Nature B.V
• Subjects: Animals; Benzodioxoles - pharmacology; Benzodioxoles - therapeutic use; Biochemistry; Biological and Medical Physics; Biomedical and Life Sciences; Biophysics; Biotechnology; Cell Biology; Collagen - metabolism; Down-Regulation - drug effects; Hepatic Veno-Occlusive Disease - chemically induced; Hepatic Veno-Occlusive Disease - drug therapy; Hepatic Veno-Occlusive Disease - enzymology; Hepatic Veno-Occlusive Disease - immunology; Kupffer Cells - drug effects; Kupffer Cells - immunology; Laminin - metabolism; Life Sciences; Liver - drug effects; Liver - immunology; Liver - injuries; Liver - metabolism; Male; Mast Cells - drug effects; Mast Cells - immunology; Matrix Metalloproteinase Inhibitors; Monocrotaline - adverse effects; Neutrophils - drug effects; Neutrophils - immunology; Original Paper; Peroxidase - antagonists & inhibitors; Pharmacology/Toxicology; Phenols - pharmacology; Phenols - therapeutic use; Protease Inhibitors - pharmacology; Protease Inhibitors - therapeutic use; Rats; Rats, Sprague-Dawley; Tissue Inhibitor of Metalloproteinase-1 - metabolism; Up-Regulation - drug effects; Matrix metalloproteinase-9; Kupffer cell; Laminin; Monocrotaline; Sinusoidal obstruction syndrome; Mast cell; Neutrophil
• ISSN: 1085-9195; 1559-0283
• DOI: 10.1007/s12013-011-9215-3

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.