Toxicological studies on a benzofurane derivative. II. Demonstration of peroxisome proliferation in rat liver.
The uricosuric drug benzbromarone (3,5-dibromo-4-hydroxyphenyl)-1-(2-ethyl-3-benzofuranyl)methanone, a benzofurane derivative, was studied for its effects on parameters related to hepatic peroxisome proliferation. Groups of male F-344 rats were fed either basal diet, the peroxisome proliferator clofibrate at 5000 ppm as a comparison compound, or benzbromarone at two doses, 1000 and 2000 ppm. Benzbromarone and clofibrate produced hepatomegaly and increases in the activities of catalase, acyl CoA oxidase, malate dehydrogenase, and glycerol-3-phosphate dehydrogenase. Benzbromarone and clofibrate also both induced similar histologic and ultrastructural changes in hepatocytes, including induction of peroxisomes. Therefore, benzbromarone acted as a peroxisome-proliferating agent in rats under these conditions. Benzbromarone differs from other peroxisome proliferators in its chemical structure, uricosuric action, and the morphology of liver peroxisomes that were induced by exposure.
Butler
E G
EG
American Health Foundation, Valhalla, New York 10595.
Ichida
T
T
Maruyama
H
H
Schulte-Hermann
R
R
Williams
G M
GM
D000818:Animals; D001553:Benzbromarone / Q000633:toxicity*; D001835:Body Weight; D002994:Clofibrate / Q000494:pharmacology; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D008297:Male; D008830:Microbodies / Q000187:drug effects* / Q000648:ultrastructure; D008854:Microscopy, Electron; D009929:Organ Size; D051381:Rats; D011916:Rats, Inbred F344; D014503:Urate Oxidase / Q000378:metabolism
D001553:Benzbromarone; D014503:Urate Oxidase; D002994:Clofibrate