Interferon-alpha preserves erythrocyte and hepatocyte ATPase activities from liver damage induced by prolonged bile duct ligation in the rat.
Interferons have been used to treat chronic hepatitis owing to their antiviral properties. However, now interferons are recognized to inhibit collagen production. Because fibrosis has been associated with liver damage and dysfunction, the effects of interferon-alpha 2b on biliary obstruction-induced cirrhosis were investigated. Obstructive jaundice was induced in male Wistar rats (ca. 200 g) by double ligation and division of the common bile duct. Control rats were sham operated. Interferon-alpha 2b (IFN-alpha; 1000 000 IU per rat) was administered subcutaneously daily after surgery. The animals were sacrificed after 4 weeks of bile duct ligation (BDL) or sham operation. Bilirubins and serum enzyme activities of alkaline phosphatase and gamma-glutamyl transpeptidase (determined as markers of liver damage) increased several-fold after BDL. Erythrocyte and hepatocyte plasma membrane Na+/K+- and Ca2+-ATPase activities decreased significantly in the BDL group. Administration of IFN-alpha to BDL rats resulted in a partial normalization of serum markers of liver damage. The normal activity of both ATPases on erythrocyte and hepatocyte plasma membranes was completely preserved by IFN-alpha. It is concluded that interferons possess interesting hepatoprotective effects not related to their antiviral properties but probably associated with their antifibrogenic effect.
Muriel
P
P
Departmento de Farmacología y Toxicología, Centro de Investigación y de Estudios Avanzados del I.P.N., Mexico.
D000818:Animals; D001652:Bile Ducts / Q000502:physiology*; D000252:Calcium-Transporting ATPases / Q000097:blood / Q000187:drug effects*; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000201:enzymology*; D016898:Interferon-alpha / Q000494:pharmacology*; D008026:Ligation / Q000009:adverse effects; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000097:blood / Q000187:drug effects*
D016898:Interferon-alpha; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase