Carvacrol Downregulates Lysyl Oxidase Expression and Ameliorates Oxidative Stress in the Liver of Rats with Carbon Tetra
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ORIGINAL RESEARCH ARTICLE
Carvacrol Downregulates Lysyl Oxidase Expression and Ameliorates Oxidative Stress in the Liver of Rats with Carbon Tetrachloride-Induced Liver Fibrosis Roohollah Mohseni1,2 • Jamshid Karimi1 Mohammad Hashemnia3
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Heidar Tavilani1 • Iraj Khodadadi1
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Received: 2 November 2018 / Accepted: 20 August 2019 Ó Association of Clinical Biochemists of India 2019
Abstract In the current study, we aimed to investigate the effect of carvacrol on the suppression of liver fibrosis progression through targeting lysyl oxidase (LOX) expression. The rats received carbon tetrachloride (CCl4) intraperitoneally and carvacrol orally for 10 weeks. Liver damage was evaluated by measuring the serum level of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase and hepatic oxidative stress parameters including total antioxidant capacity, total thiol group and total oxidant status spectrophotometry and malondialdehyde fluorometrically. Extracellular deposition of collagen was detected using Masson’s trichrome standing. Furthermore the gene expression of lysyl oxidase homolog 2 (Loxl2) was analyzed using quantitative reverse transcription-polymerase chain reaction. And then the protein level of LOX was detected in liver tissue by western blot method. Carvacrol administration normalized serum biochemical parameters and improved oxidative stress status in liver homogenate of CCl4 treated rats. Collagen fiber bundles in interlobular spaces were decreased remarkably by carvacrol treatment. Also, carvacrol downregulated hepatic gene expression of Loxl2 and protein level of LOX. Our data clearly revealed that carvacrol suppresses progression of liver fibrosis development via attenuating of liver damage and oxidative stress status as well as via & Jamshid Karimi [email protected] 1
Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
2
Student Research Committee, Hamadan University of Medical Sciences, Hamadan, Iran
3
Department of Pathobiology, Veterinary Medicine Faculty, Razi University, Kermanshah, Iran
downregulation of hepatic gene expression of Loxl2 and protein level of LOX. Keywords Carvacrol Hepatic fibrosis Lysyl oxidase Carbon tetrachloride Abbreviations CCl4 Carbon tetrachloride LOX Lysyl oxidase ECM Extracellular matrix ALT Alanine aminotransferas AST Aspartate aminotransferase ALP Alkaline phosphatase TAC Total antioxidant capacity –SH Total thiol group TOS Total oxidant status MDA Malondialdehyde
Introduction Over the last years, the regression of advanced liver fibrosis has become a global concern. Over time chronic liver inflammation can be lead to liver fibrosis and subsequently develop into cirrhosis if left untreated [1]. Excessive deposition of extracellular matrix (ECM) components and collagen cross-linking limit liver fibrosis regression. Collagen cross-linking is catalyzed by lysyl oxidase (LOX) enzyme. LOX is an extracellular copper-dependent enzyme that catalyzes covalent cross-linkage for
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