Furylfuramide-induced hepatic necrosis in mice and its modification by phenobarbital

Abstract

Oral administration of furylfuramide (2-(2-furyl)-3-(5-nitro-2-furyl) acrylamide), used as an antimicrobial food preservative until recently, caused centrolobular coagulation necrosis of the liver of the mouse (ddYS, male) in the degree corresponding to the doses. The recovery process after a single oral administration was characteristic: the necrotic cells were laden with calcium and replaced by foreign body granuloma accompanied by multinucleate giant cells. Complete healing ensued in about a month. Phenobarbital pretreatment reduced injurious effect of furylfuramide on the liver with preservation of the centrolobular region. In this case necrosis occurred in the intermediate zone in a ring-like shape. This indicates enhanced detoxication of furylfuramide by microsomal drug metabolizing enzyme(s) of the liver cells induced by phenobarbital.