title: The antifibrogenic effect of etanercept on development of liver cirrhosis induced by thioacetamide in rats.
abstract: Liver cirrhosis is an elevating cause of morbidity and mortality worldwide. TNF-α/TNF-R1 signal is implicated in progression of many liver diseases. This study provides histological and ultrastructural view that clarifies the effect of etanercept, a TNF-α inhibitor, on development of thioacetamide (TAA)-induced liver cirrhosis and the accompanied hemosiderosis in rats, highlighting the implication and distribution pattern of hepatic TNF-R1. Sixty male albino rats (Rattus norvegicus) were equally randomized into three groups. Group I served as the control. Liver cirrhosis was triggered in the other two groups by intraperitoneal injection of TAA twice a week for five months. Group II received TAA only, while group III subcutaneously injected with etanercept one hour before TAA, along five months. At the end of the experiment, blood was collected for biochemical analysis and livers were excised for histological, immunohistochemical, and electron microscopical preparations. Rats treated with TAA only developed hepatic cirrhosis accompanied by massive deposition of hemosiderin; strong and widespread expression of hepatic TNF-R1 in sinusoidal endothelial cells (SECs), Kupffer cells (KCs), and many hepatocytes; and frequent appearance of fibrogenic, plasma, and mast cells, at the ultrastructural level. By contrast, administration of etanercept diminished the expression of TNF-R1, attenuated the accumulation of collagen and hemosiderin, and preserved the hepatic histoarchitecture. In conclusion, TNF-α signal via TNF-R1 may be implicated in the mechanism of fibrogenesis and the associated hemosiderosis. Etanercept may provide a promising therapeutic approach not only for attenuating the progression of fibrogenesis, but also for hepatic iron overload-associated disorders.
authors.affiliation: a Department of Zoology, Faculty of Science , Beni-Suef University , Beni-Suef , Egypt.
authors.forename: Manal
authors.initials: M
authors.lastname: Abdul-Hamid
authors.affiliation: a Department of Zoology, Faculty of Science , Beni-Suef University , Beni-Suef , Egypt.
authors.forename: Rasha R
authors.initials: RR
authors.lastname: Ahmed
authors.affiliation: a Department of Zoology, Faculty of Science , Beni-Suef University , Beni-Suef , Egypt.
authors.forename: Nadia
authors.initials: N
authors.lastname: Moustafa
authors.affiliation: a Department of Zoology, Faculty of Science , Beni-Suef University , Beni-Suef , Egypt.
authors.forename: Rehab
authors.initials: R
authors.lastname: Nady
mesh_terms: D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D003094:Collagen / Q000378:metabolism; D019610:Cytoprotection; D000068800:Etanercept / Q000494:pharmacology*; D006485:Hemosiderin / Q000378:metabolism; D006486:Hemosiderosis / Q000139:chemically induced / Q000517:prevention & control; D007150:Immunohistochemistry; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D046529:Microscopy, Electron, Transmission; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D013853:Thioacetamide; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D020011:Protective Agents; D047888:Receptors, Tumor Necrosis Factor, Type I; C506237:Tnfrsf1a protein, rat; D014409:Tumor Necrosis Factor-alpha; D013853:Thioacetamide; D003094:Collagen; D006485:Hemosiderin; D000068800:Etanercept
keywords: Etanercept; TNF-R1; TNF-α; liver cirrhosis; thioacetamide