Study of plasma protein C and inflammatory pathways: Biomarkers for dimethylnitrosamine-induced liver fibrosis in rats

The present investigation was designed to identify potential biomarker(s) and assess the involvement of inflammatory pathway in dimethylnitrosamine (DMN)-induced liver fibrosis in rats. Following DMN-treatment (10 mg/ml/kg, i.p., given three consecutive days each week for 4 weeks) body and liver wei...

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Published in:European journal of pharmacology Vol. 575; no. 1; pp. 158 - 167
Main Authors: Saha, Joy K., Xia, Jinqi, Sandusky, George E., Chen, Yun-Fei, Gerlitz, Bruce, Grinnell, Brian, Jakubowski, Joseph A.
Format: Journal Article
Language:English
Published: Amsterdam Elsevier B.V 01.12.2007
Elsevier
Subjects:
Animals
Biological and medical sciences
Biomarker
Biomarkers - blood
C-Reactive Protein - metabolism
Chemokine
Chemokines - blood
Dimethylnitrosamine
Fibrinolytic Agents - blood
gamma-Glutamyltransferase - blood
Gastroenterology. Liver. Pancreas. Abdomen
Haptoglobins - metabolism
Humans
Hyaluronic Acid - blood
Immunohistochemistry - methods
Inflammation
Inflammation - metabolism
Inflammation - pathology
Intercellular Adhesion Molecule-1 - blood
Liver Cirrhosis - blood
Liver Cirrhosis - chemically induced
Liver Cirrhosis - diagnosis
Liver Cirrhosis - pathology
Liver enzyme
Liver fibrosis
Liver histopathology
Liver. Biliary tract. Portal circulation. Exocrine pancreas
Macrophage Colony-Stimulating Factor - blood
Medical sciences
Neutrophils - metabolism
Other diseases. Semiology
Pharmacology. Drug treatments
Protein C
Protein C - metabolism
Rats
Rats, Sprague-Dawley
Serum Albumin - metabolism
sICAM-1
Time Factors
sICAM-1
Chemokine
Liver histopathology
Biomarker
Dimethylnitrosamine
Liver enzyme
Protein C
Inflammation
Liver fibrosis
Hepatic fibrosis
Biological fluid
Rat
Enzyme
Rodentia
Biological marker
Hepatic disease
Blood plasma
Vertebrata
Anatomic pathology
Mammalia
Histopathology
Animal
Digestive diseases
ISSN:0014-2999, 1879-0712
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Summary:The present investigation was designed to identify potential biomarker(s) and assess the involvement of inflammatory pathway in dimethylnitrosamine (DMN)-induced liver fibrosis in rats. Following DMN-treatment (10 mg/ml/kg, i.p., given three consecutive days each week for 4 weeks) body and liver weights were significantly decreased concurrent with increasing severity of liver damage assessed by bridging fibrosis, a histopathologic assessment and characteristic of human liver disease. Protein C along with albumin, C-reactive-protein (CRP), haptoglobin and total protein were significantly reduced and correlated with changes in liver histopathology. Biochemical markers of liver functions were significantly increased and correlated with changes in liver histopathology and plasma levels of protein C. Soluble intracellular-adhesion-molecule-1 (sICAM-1) levels were increased significantly but were poorly correlated with histopathology and protein C levels. Inflammatory chemokines and other analytes, monocyte-chemoattractant-protein-1 and 3 (MCP-1 and MCP-3), macrophage-colony-stimulating-factor (M-CSF) were significantly increased during the disease progression, whereas macrophage-derived-chemokine (MDC) and CRP were significantly suppressed. Circulating neutrophils and monocytes were also increased along with disease progression. The differential changes in sICAM-1, hyaluronic acid, gamma-glutamyltranspeptidase (GGT), neutrophil and other inflammatory chemokines suggest the involvement of inflammatory pathways in DMN-induced liver fibrosis. In conclusion, the progressive changes in protein C along with other noninvasive biochemical parameters whose levels were significantly correlated with disease progression may serve as biomarkers for pharmacological assessment of targeted therapy for liver fibrosis.
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ISSN:0014-2999
1879-0712
DOI:10.1016/j.ejphar.2007.07.052