Portal, but not lobular, macrophages express matrix metalloproteinase‐9: association with the ductular reaction and fibrosis in chronic hepatitis C

Gadd, Victoria L.; Melino, Michelle; Roy, Sandrine; Horsfall, Leigh; O’Rourke, Peter; Williams, Millicent R.; Irvine, Katharine M.; Sweet, Matthew J.; Jonsson, Julie R.; Clouston, Andrew D.; Powell, Elizabeth E.

doi:10.1111/liv.12050

Cited by 44 publications

(55 citation statements)

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“…In rodent models of ongoing liver injury, macrophages/KCs play a key role in the hepatic response to chronic inflammation [62]. The pattern of expression of membrane receptors and antigens like CD68 has been shown to reflect the state of and a-R-lipoic acid (F).…”

Section: Discussionmentioning

confidence: 99%

Curcumin, Silybin Phytosome^® and α‐R‐Lipoic Acid Mitigate Chronic Hepatitis in Rat by Inhibiting Oxidative Stress and Inflammatory Cytokines Production

Ali

Darwish

Ismail

2015

Basic Clin Pharma Tox

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Chronic hepatitis is recognized as a worldwide health problem that gradually progresses towards cirrhosis and hepatocellular carcinoma. Despite the large number of experiments using animal models for allergic hepatitis, it is still difficult to produce a picture of chronic hepatitis. Therefore, this study was conducted to introduce an animal model approximating to the mechanism of chronicity in human hepatitis. The study also aimed to examine the hepatoprotective effects of curcumin, silybin phytosome â and a-R-lipoic acid against thioacetamide (TAA)-induced chronic hepatitis in rat model. TAA was administered intraperitoneally at a dose of 200 mg/kg three times weekly for 4 weeks. At the end of this period, a group of rats was killed to assess the development of chronic hepatitis in comparison with their respective control group. TAA administration was then discontinued, and the remaining animals were subsequently allocated into four groups. Group 1 was left untreated, whereas groups 2-4 were allowed to receive daily oral doses of curcumin, silybin phytosome â or a-R-lipoic acid, respectively, for 7 weeks. Increases in hepatic levels of malondialdehyde associated with TAA administration were inhibited in groups receiving supplements. Furthermore, glutathione depletion, collagen deposition, macrophage activation and nuclear factor jappa-B expression as well as tumour necrosis factor-a and interleukin-6 levels were significantly decreased in response to supplements administration. Serological analysis of liver function and liver histopathological examination reinforced the results. The above evidence collectively indicates that the antioxidant and anti-inflammatory activities of curcumin, silybin phytosome â and a-R-lipoic acid may confer therapeutic efficacy against chronic hepatitis.

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Section: Discussionmentioning

confidence: 99%

Curcumin, Silybin Phytosome^® and α‐R‐Lipoic Acid Mitigate Chronic Hepatitis in Rat by Inhibiting Oxidative Stress and Inflammatory Cytokines Production

Ali

Darwish

Ismail

2015

Basic Clin Pharma Tox

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“…Moreover, clinical studies discovered a link between the increased levels of MMPs, including MMP-9, and fragments of type-IV collagen in cirrhosis. 53 Furthermore, liver MMP-9 expression and activity have also been associated with the stage of fibrosis in chronic hepatitis C. 54 In a study conducted by Kamari and colleagues, 4 decreased liver fibrosis in interleukin-1 (IL-1) α-deficient mice fed with atherogenic diet (high-fat/cholesterol and cholate diet, HFHCD) was associated with lower MMP-9 expression independent of liver steatosis. These results, together with our present findings, illustrate the positive association between MMP-9 expression and liver fibrosis in response to high-cholesterol/cholate consumption.…”

Section: Discussionmentioning

confidence: 99%

The role of iNOS in cholesterol-induced liver fibrosis

Anavi

Eisenberg-Bord

Hahn-Obercyger

et al. 2015

Laboratory Investigation

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Accumulation of cholesterol in the liver is associated with the development of non-alcoholic steatohepatitis-related fibrosis. However, underlying mechanisms are not well understood. The present study investigated the role of inducible nitric oxide synthase (iNOS) in cholesterol-induced liver fibrosis by feeding wild-type (WT) and iNOS-deficient mice with control or high-cholesterol diet (HCD) for 6 weeks. WT mice fed with HCD developed greater liver fibrosis, compared with iNOS-deficient mice, as evident by Sirius red staining and higher expression levels of profibrotic genes. Enhanced liver fibrosis in the presence of iNOS was associated with hypoxia-inducible factor-1a stabilization, matrix metalloproteinase-9 expression, and enhanced hepatic DNA damage. The profibrotic role of iNOS was also demonstrated in vivo using a selective inhibitor of iNOS as well as in vitro in a rat liver stellate cell line (HSC-T6). In conclusion, these findings suggest that iNOS is an important mediator in HCD-induced liver fibrosis.Laboratory Investigation (2015) 95, 914-924;

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“…In Addition to elevated pro-inflammatory cytokines, it was observed that metabolic dysfunctions such as insulin resistance are associated with reduced protective adipokines (such as adiponectin (Hotta et al, 2000)), and increased macrophage accumulation in the liver and adipose tissue (Lanthier et al, 2010). In particular, CD4 (þ) and CD8 (þ) T cells infiltration increases in the liver (Gadd et al, 2013). Nevertheless, the mechanisms of the inflammatory response related to MetS are far from been completely elucidated.…”

Section: Inflammation and Er Stress Induce Insulin Resistance In Metsmentioning

confidence: 99%

Metabolic syndrome and nonalcoholic fatty liver disease: Is insulin resistance the link?

Asrih

Jornayvaz

2015

Molecular and Cellular Endocrinology

276

196

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Portal, but not lobular, macrophages express matrix metalloproteinase‐9: association with the ductular reaction and fibrosis in chronic hepatitis C

Abstract: These findings demonstrate significant regional differences in macrophage phenotypes, suggesting that there are at least two populations of liver macrophages. We propose that these populations have distinct contributions to the pathogenesis of chronic HCV-related liver disease.

Cited by 44 publications

References 49 publications

Curcumin, Silybin Phytosome^® and α‐R‐Lipoic Acid Mitigate Chronic Hepatitis in Rat by Inhibiting Oxidative Stress and Inflammatory Cytokines Production

Curcumin, Silybin Phytosome^® and α‐R‐Lipoic Acid Mitigate Chronic Hepatitis in Rat by Inhibiting Oxidative Stress and Inflammatory Cytokines Production

The role of iNOS in cholesterol-induced liver fibrosis

Metabolic syndrome and nonalcoholic fatty liver disease: Is insulin resistance the link?

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Portal, but not lobular, macrophages express matrix metalloproteinase‐9: association with the ductular reaction and fibrosis in chronic hepatitis C

Abstract: These findings demonstrate significant regional differences in macrophage phenotypes, suggesting that there are at least two populations of liver macrophages. We propose that these populations have distinct contributions to the pathogenesis of chronic HCV-related liver disease.

Cited by 44 publications

References 49 publications

Curcumin, Silybin Phytosome® and α‐R‐Lipoic Acid Mitigate Chronic Hepatitis in Rat by Inhibiting Oxidative Stress and Inflammatory Cytokines Production

Curcumin, Silybin Phytosome® and α‐R‐Lipoic Acid Mitigate Chronic Hepatitis in Rat by Inhibiting Oxidative Stress and Inflammatory Cytokines Production

The role of iNOS in cholesterol-induced liver fibrosis

Metabolic syndrome and nonalcoholic fatty liver disease: Is insulin resistance the link?

Contact Info

Product

Resources

About

Curcumin, Silybin Phytosome^® and α‐R‐Lipoic Acid Mitigate Chronic Hepatitis in Rat by Inhibiting Oxidative Stress and Inflammatory Cytokines Production

Curcumin, Silybin Phytosome^® and α‐R‐Lipoic Acid Mitigate Chronic Hepatitis in Rat by Inhibiting Oxidative Stress and Inflammatory Cytokines Production