Toxicological significance of hepatic responses to furylfuramide(AF-2) in the rat.
In male rats fed furylfuramide [2-(2-furyl)-3-(5-nitro-2-furyl)-acrylamide, AF-2] at a dietary level of 0.1%, a marked increase in the liver weight was observed with a concomitant reduction of microsomal mixed function oxidase activity. To clarify the significance of these hepatic responses to furylfuramide, a series of biochemical parameters that reflect hepatotoxicity was measured. The most significant elevations were seen in hepatic glycogen and glucose 6-phosphate dehydrogenase levels over 29-day feeding interval. A marked decrease was observed in mixed-function oxidases and glucose 6-phosphatase activities. Moderate decreases were seen in several other parameters, especially in the early phase of feeding. Measurement of serum parameters showed significant elevation in cholesterol and a transient increase in serum glutamic pyruvic transaminase. A comparative study demonstrated small differences between furylfuramide and carbon tetrachloride in their effects on hepatic parameters. The furylfuramide-induced changes appear to be reversible within 14 days after withdrawal of furylfuramide from the diet. Reduction of mixed-function oxidase activity by furylfuramide might be caused partly by the elevation of heme degrading enzyme. The results indicate a dysfunction of drug-metabolizing activity and acute and slight toxication of the liver by furylfuramide.
D000284:Administration, Oral; D000410:Alanine Transaminase / Q000097:blood; D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001786:Blood Glucose; D002251:Carbon Tetrachloride / Q000633:toxicity; D002784:Cholesterol / Q000097:blood; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005668:Furylfuramide / Q000633:toxicity*; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009581:Nitrofurans / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D001786:Blood Glucose; D009581:Nitrofurans; D005668:Furylfuramide; D003577:Cytochrome P-450 Enzyme System; D002784:Cholesterol; D002251:Carbon Tetrachloride; D006899:Mixed Function Oxygenases; D005954:Glucosephosphate Dehydrogenase; D000633:Aminopyrine N-Demethylase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005952:Glucose-6-Phosphatase