Lysyl oxidase and collagenase in experimental acute and chronic liver injury.
ABSTRACT Lysyl oxidase and collagenase activities were measured in experimental acute and chronic liver injury in mice and rats, and correlated with collagen synthesis and accumulation. Acute liver injury was induced in mice and rats by a single dose of carbon tetrachloride given by gavage, and also in mice by a single injection of murine hepatitis virus. Chronic liver injury was induced in rats by repeated injections of carbon tetrachloride. Elevated plasma glutamic oxaloacetic transaminase levels, increased hepatic prolyl hydroxylase activity, and increased synthesis of collagen-bound hepatic hydroxyproline occurred in animals with acute as well as with chronic liver injury. However, only chronic liver injury appeared to be associated with fibrosis, increased collagen-bound hydroxyproline content, increased hepatic lysyl oxidase and collagenase activities, as well as with increased serum lysyl oxidase activity. These data suggest that lysyl oxidase and collagenase may play an important role in the collagen accumulation associated with hepatic fibrosis.
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ABSTRACT: Chronic alcoholism is associated with fatty liver and fibrosis characterized by collagen accumulation. Seeds of fenugreek, an annual herb, are reported to possess hepatoprotective activity. The study aims to investigate the effects of fenugreek seed polyphenol extract (FPEt) on liver lipids and collagen in experimental hepatotoxic rats. Hepatotoxicity was induced in male albino Wistar rats by administrating ethanol (6 g/kg per day) for 30 days. Control rats were given isocaloric glucose solution. FPEt was co-administered with ethanol at a dose of 200 mg/kg per day for the next 30 days. Silymarin was used as a positive control. Ethanol treatment caused increase in plasma and liver lipids, together with alterations in collagen content and properties. Administration of FPEt to alcohol-fed rats significantly improved lipid profile and reduced collagen content, crosslinking, aldehyde content and peroxidation. The effects were comparable with that of silymarin. FPEt administration had a positive influence on both lipid profile and on the quantitative and qualitative properties of collagen in alcoholic liver disease. The protective effect is presumably due to the bioactive phytochemicals in fenugreek seeds.Cell Biology and Toxicology 12/2007; 23(6):373-83. · 2.34 Impact Factor
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ABSTRACT: Under hypoxia, tumour cells undergo genetic and adaptive changes that allow their survival. Previously, we reported that high expression of hypoxia-inducible factor (HIF)-1 was a significant predictive factor for recurrence in hepatocellular carcinoma (HCC). Hypoxia also stimulates expression of procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD) genes via the HIF-1 pathway. The aim was to evaluate the relationship between hypoxia stress and expression of PLOD genes in HCC in vitro and to identify a new prognostic marker in HCC patients. The PLOD2 expression was assessed under hypoxia in hepatoma cell lines and characterized in 139 HCC samples following hepatic resection using microarray experiments, quantitative RT-PCR and immunohistochemistry. Prognostic factors in HCC patients were assessed using univariate and multivariate analyses. The PLOD2 expression was induced under the hypoxia in vitro. Disease-free survival in the high PLOD2 expression group of HCC patients was significantly shorter when compared with the low-expression group (P = 0.002). In a subset of HCCs, we found that the PLOD2 expression of microarray was correlated with data of quantitative RT-PCR and immunohistochemistry. Of clinicopathological factors, PLOD2 expression was significantly correlated with tumour size (P = 0.022) and macroscopic intrahepatic metastasis (P = 0.049). In univariate analysis, six prognostic factors (tumour multiplicity, macroscopic intrahepatic metastasis, histological grade, microscopic portal invasion, microscopic intrahepatic metastasis and PLOD2 expression) were significant for disease-free survival. PLOD2 expression was identified as a significant, independent factor of poor prognosis (P = 0.013). PLOD2 is a potential novel prognostic factor for HCC patients following surgery.Liver international: official journal of the International Association for the Study of the Liver 08/2011; 32(1):110-8. · 3.87 Impact Factor
- Hepatology Research 09/2009; 39(8):748-50. · 2.07 Impact Factor