The influence of interferon alpha on the rat liver injured by chronic administration of carbon tetrachloride.
Due to their complex and not fully known etiopathogenesis as well as difficulties in treatment, chronic hepatitis and cirrhosis still remain one of the main problems of hepatologists. Nowadays, the use of IFN alpha is considered the most effective method of treatment in chronic hepatitis. Recently, a new property of IFN, i.e. its effects on the reduction of fibrosis, has been discovered. The aim of the paper was to examine the effects of IFN alpha on biochemical parameters (AlAt and AspAt activities), on the metabolic function of the liver and its morphologic picture observed under the light and electron microscope after the 3- and 6-week CCl4-induced damage. The experiments were carried out in Wistar male rats. To evaluate the liver function, the test of aminophenazone elimination in the isolated perfused rat livers was used according to Miller modified by Hafte. Additionally, AspAt and AlAt activities were determined. The liver specimens were analysed under the light and electron microscope and using immunohistochemical methods. The findings show that after the 3-week CCl4-induced liver damage, IFN alpha does not significantly affect AlAt and AspAt activities, irrespective of the dose used. IFN alpha administered after the 6-week damage significantly changes those activities when the doses used are high. It was found that carbon tetrachloride does not result in evident cirrhotic changes, however it activates Ito cells, causes focal retraction of the stroma and fibrosis. The increased number of Ito cells in Disse's space observed in immunohistochemical and ultrastructural examinations is indicative of the activation of liver fibrotic processes following CCl4 administration in both variants used. IFN alpha substantially weakens fibrogenesis of the CCl4-damaged liver which is visible in the decreased number of Ito cells and weaker expression of the stroma retraction. Moreover, IFN alpha administered to the experimental animals after the CCl4-induced injury of the liver increases aminophenazone clearance, especially when used in higher doses. Positive effects of IFN confirmed in the studies suggest that the drug may be used in patients with chronic hepatitis and early cirrhosis since it is likely not only to eliminate the virus but also to improve the liver function and reduce fibrosis.
Madro
Agnieszka
A
Department of Gastroenterology, Medical University of Lublin.
Słomka
Maria
M
Celiński
Krzysztof
K
Chibowski
Daniel
D
Czechowska
Grazyna
G
Kleinrok
Zdzisław
Z
Karpińska
Agnieszka
A
D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000503:physiopathology*; D056487:Chemical and Drug Induced Liver Injury, Chronic / Q000503:physiopathology*; D005234:Fatty Liver / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D016898:Interferon-alpha / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D008111:Liver Function Tests; D008297:Male; D008854:Microscopy, Electron; D051381:Rats; D017208:Rats, Wistar
D016898:Interferon-alpha