[Hepatotoxicity of (chloro-2-ethyl)-1-cyclohexyl-3-nitroso-1-urea (CCNU) in the rat]

Few cases of liver involvement have been reported in patients receiving treatment with CCNU. CCNU is an anti-tumoral agent used in the treatment of leukemia, Hodgkin's disease and bronchial or cerebral tumors. A single daily dose of 20 or 50 mg/kg CCNU in female Wistar rats induces an important increase of transaminases, reaching 10 times initial level between day 2 and day 6, followed by a second and moderate increase between day 21 and day 28. Three-fold increased alkaline phosphatases and conjugated hyperbilirubinemia were noted for the two doses, and was greater for the higher dose. Histological and ultrastructural studies showed two types of lesions: during the first phase of transaminase elevation, edema and inflammatory infiltration of the portal spaces; during the second phase of transaminases elevation, numerous bundles of pericanalicular microfilaments and severe dilation of the biliary tract. Hepatic cells had few alterations although some necrotic foci were observed, particularly at the higher dose. So CCNU induced an intrahepatic cholestasis with pericholangitis in the rat.