Heat shock protein 47 as indispensible participant in liver fibrosis: Possible protective effect of lactoferrin

Lactoferrin (LF) was previously suggested to have a protective effect against liver fibrosis by preventing hepatic stellate cells (HSCs) activation. The effect of LF on heat shock protein 47 (HSP47) has not yet been studied so this study was designed to investigate LF effect on HSP47 as a potential...

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Published in:IUBMB life 2018-08, Vol.70 (8), p.795-805
Main Authors: Rizk, Fatma H., Sarhan, Naglaa I., Soliman, Nema A., Ibrahim, Marwa A. A., Abd‐Elsalam, Marwa, Abd‐Elsalam, Sherief
Format: Article
Language:English
Subjects:
Actin
Animals
Antioxidants
Antioxidants - administration & dosage
Cirrhosis
Collagen
Fibrosis
Gene Expression Regulation - drug effects
Heat shock proteins
Hepatic Stellate Cells - drug effects
Hepatic Stellate Cells - metabolism
HSP47
HSP47 Heat-Shock Proteins - antagonists & inhibitors
HSP47 Heat-Shock Proteins - genetics
Humans
Hydroxyproline
Lactoferrin
Lactoferrin - administration & dosage
Liver
Liver - drug effects
Liver - pathology
Liver cirrhosis
Liver Cirrhosis - drug therapy
Liver Cirrhosis - genetics
Liver Cirrhosis - pathology
liver fibrosis
Malondialdehyde
Matrix metalloproteinase
Matrix Metalloproteinase 2 - genetics
Metalloproteinase
Nitric oxide
Rats
Rodents
Silymarin
Silymarin - administration & dosage
Smooth muscle
Stellate cells
Thioacetamide
Thioacetamide - administration & dosage
Transforming Growth Factor beta1 - genetics
Transforming growth factor-b1
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Summary:Lactoferrin (LF) was previously suggested to have a protective effect against liver fibrosis by preventing hepatic stellate cells (HSCs) activation. The effect of LF on heat shock protein 47 (HSP47) has not yet been studied so this study was designed to investigate LF effect on HSP47 as a potential target for management of liver fibrosis and comparing it with silymarin (SM) in a thioacetamide (TAA)‐induced liver fibrosis model. Rats were divided into four groups; normal control, TAA (TAA‐treated), LF (LF + TAA‐treated), and SM (SM + TAA‐treated). After 6 weeks, both LF and SM improved the grade of cirrhosis, reduced collagen fibers deposition, inactivated HSCs, significantly decreased elevated liver enzymes, HSP47, hydroxyproline content, transforming growth factor‐beta 1, matrix metalloproteinase‐2, 8‐hydroxydeoxyguanosine, malondialdehyde, nitric oxide levels and the percentage of alpha smooth muscle actin positive HSCs compared with TAA group. Moreover, LF significantly increased the total antioxidant capacity compared with TAA group. It could be concluded that LF is a promising antifibrotic drug and could be considered as one of the HSP47 inhibitors but SM is still more potent. © 2018 IUBMB Life, 70(8):795–805, 2018
ISSN:1521-6543
1521-6551
DOI:10.1002/iub.1884