Improvement of hepatic fibrosis by leukotriene inhibition in cholestatic rats
Chronic liver disease is characterized by inflammation and fibrosis. Angiogenesis which leading to new vascu-lature may have prognostic value in disease progression. This study examined the implication of 5-lipoxy-genase pathway and angiogenic factors in hepatic fi-brosis progression and whether, th...
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| Format: | Article |
| Language: | English |
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Elsevier
2009-01-01
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| Series: | Annals of Hepatology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1665268119318101 |
| _version_ | 1818602832277798912 |
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| author | Sahar EL-Swefy, Dr. Samia I. Hassanen |
| author_facet | Sahar EL-Swefy, Dr. Samia I. Hassanen |
| author_sort | Sahar EL-Swefy, Dr. |
| collection | DOAJ |
| description | Chronic liver disease is characterized by inflammation and fibrosis. Angiogenesis which leading to new vascu-lature may have prognostic value in disease progression. This study examined the implication of 5-lipoxy-genase pathway and angiogenic factors in hepatic fi-brosis progression and whether, the inhibition of arachidonic acid cascade product (cysteinyl leukot-rienes) can represent a potential target for therapy. Cholestasis and subsequent fibrosis was induced by common bile duct ligation and resection (BDL) for 5 weeks in rats. After surgery, Cysteinyl leukotrienes antagonist (montelukast) was orally and daily administrated (10 mg/kg) for 34 days. Sham operated and drug control groups received either saline or montelukast immediately after operation. BDL significantly increased liver hydroxyproline (Hp), nuclear factor kappa B (NF-Kβ), transforming growth factor beta (TGF-β), tissue inhibitor metalloproteinase (TIMP-1), vascular endothelial growth factor (VEGF), and reduced the level of matrix metalloproteinase 9 (MMP-9). On the other hand, montelukast treatment reversed all these biochemical parameters and ameliorated histopatho-logical changes which previously induced by BDL. Findings of the present study suggest that montelukast treatment may favor collagenolytic activity through modulating hepatic expression of TGF-β, NF-κβ, and MMP-9/TIMP-1 ratio. Amelioration of necroinflam-matory liver injury and fibrogenesis may support such assumption. |
| first_indexed | 2024-12-16T13:13:32Z |
| format | Article |
| id | doaj.art-e7bc700d5da8417da6406cc958d8e29d |
| institution | Directory Open Access Journal |
| issn | 1665-2681 |
| language | English |
| last_indexed | 2024-12-16T13:13:32Z |
| publishDate | 2009-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Annals of Hepatology |
| spelling | doaj.art-e7bc700d5da8417da6406cc958d8e29d2022-12-21T22:30:33ZengElsevierAnnals of Hepatology1665-26812009-01-01814149Improvement of hepatic fibrosis by leukotriene inhibition in cholestatic ratsSahar EL-Swefy, Dr.0Samia I. Hassanen1Biochemistry Dept., Faculty of Pharmacy, Zagazig Universit; Address for correspondence: Dr. Sahar EL-SwefyAgricultural Research Center, EgyptChronic liver disease is characterized by inflammation and fibrosis. Angiogenesis which leading to new vascu-lature may have prognostic value in disease progression. This study examined the implication of 5-lipoxy-genase pathway and angiogenic factors in hepatic fi-brosis progression and whether, the inhibition of arachidonic acid cascade product (cysteinyl leukot-rienes) can represent a potential target for therapy. Cholestasis and subsequent fibrosis was induced by common bile duct ligation and resection (BDL) for 5 weeks in rats. After surgery, Cysteinyl leukotrienes antagonist (montelukast) was orally and daily administrated (10 mg/kg) for 34 days. Sham operated and drug control groups received either saline or montelukast immediately after operation. BDL significantly increased liver hydroxyproline (Hp), nuclear factor kappa B (NF-Kβ), transforming growth factor beta (TGF-β), tissue inhibitor metalloproteinase (TIMP-1), vascular endothelial growth factor (VEGF), and reduced the level of matrix metalloproteinase 9 (MMP-9). On the other hand, montelukast treatment reversed all these biochemical parameters and ameliorated histopatho-logical changes which previously induced by BDL. Findings of the present study suggest that montelukast treatment may favor collagenolytic activity through modulating hepatic expression of TGF-β, NF-κβ, and MMP-9/TIMP-1 ratio. Amelioration of necroinflam-matory liver injury and fibrogenesis may support such assumption.http://www.sciencedirect.com/science/article/pii/S1665268119318101Hepatic fibrosisinflammationangiogenesisleukotrienes antagonistrats |
| spellingShingle | Sahar EL-Swefy, Dr. Samia I. Hassanen Improvement of hepatic fibrosis by leukotriene inhibition in cholestatic rats Annals of Hepatology Hepatic fibrosis inflammation angiogenesis leukotrienes antagonist rats |
| title | Improvement of hepatic fibrosis by leukotriene inhibition in cholestatic rats |
| title_full | Improvement of hepatic fibrosis by leukotriene inhibition in cholestatic rats |
| title_fullStr | Improvement of hepatic fibrosis by leukotriene inhibition in cholestatic rats |
| title_full_unstemmed | Improvement of hepatic fibrosis by leukotriene inhibition in cholestatic rats |
| title_short | Improvement of hepatic fibrosis by leukotriene inhibition in cholestatic rats |
| title_sort | improvement of hepatic fibrosis by leukotriene inhibition in cholestatic rats |
| topic | Hepatic fibrosis inflammation angiogenesis leukotrienes antagonist rats |
| url | http://www.sciencedirect.com/science/article/pii/S1665268119318101 |
| work_keys_str_mv | AT saharelswefydr improvementofhepaticfibrosisbyleukotrieneinhibitionincholestaticrats AT samiaihassanen improvementofhepaticfibrosisbyleukotrieneinhibitionincholestaticrats |