Modifications in rat hepatobiliary function following treatment with acetone, 2-butanone, 2-hexanone, mirex, or chlordecone and subsequently exposed to chloroform.
Potentiation of haloalkane hepatonecrosis by various ketones is a well-documented observation. The present study investigates the hepatobiliary effects of such treatments. Male Sprague-Dawley rats were pretreated with acetone (A), 2-butanone (MEK), 2-hexanone (MBK), 15 mmol/kg (po), or chlordecone (CD) and its nonketonic analog, mirex (M), 50 mg/kg (po). Following the pretreatment at various time intervals ranging from 10 to 96 hr, groups of animals received a challenging dosage of CHCl3 (0.5 ml/kg, po). In a collateral experiment, groups of animals were pretreated with vehicle and 18 hr later received either 0.50, 0.75, or 1.00 ml/kg CHCl3 (po). In each case hepatobiliary function was evaluated 24 hr later using bile flow rate and plasma bilirubin concentration. The results showed (1) that the ketones alone had no effect; mirex alone increased bile flow; (2) CHCl3 alone had no effect on bile flow but slightly increased plasma bilirubin; (3) all pretreatments potentiated the effect of CHCl3 on plasma bilirubin; (4) combinations of A, MBK, or CD plus CHCl3 were cholestatic within a restricted time frame. A study of biliary tree permeability by the segmented retrograde intrabiliary injection technique, using mannitol and inulin as marker compounds, suggested that cholestasis may result from potentiation of CHCl3-induced alterations in canalicular membrane permeability.
Hewitt
L A
LA
Ayotte
P
P
Plaa
G L
GL
D000096:Acetone / Q000633:toxicity; D000818:Animals; D001646:Bile / Q000187:drug effects / Q000378:metabolism; D001659:Biliary Tract / Q000187:drug effects*; D002074:Butanones / Q000633:toxicity; D007631:Chlordecone / Q000633:toxicity; D002725:Chloroform / Q000633:toxicity*; D004347:Drug Interactions; D007659:Ketones / Q000633:toxicity*; D008099:Liver / Q000187:drug effects*; D008297:Male; D008742:Methyl n-Butyl Ketone / Q000633:toxicity; D008917:Mirex / Q000633:toxicity; D010539:Permeability; D051381:Rats; D011919:Rats, Inbred Strains
D002074:Butanones; D007659:Ketones; D000096:Acetone; C005222:methylethyl ketone; D008742:Methyl n-Butyl Ketone; D002725:Chloroform; D007631:Chlordecone; D008917:Mirex