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Aspirin disposition in rats acutely intoxicated with CCl4

✍ Scribed by Liliana Favari; Marisabel Mourelle; Joseg Luis Amezcua


Publisher
John Wiley and Sons
Year
1987
Tongue
English
Weight
495 KB
Volume
7
Category
Article
ISSN
0260-437X

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✦ Synopsis


The profile of urinary salicylate metabolites was determined after an oral administration of acetylsalicylic acid (ASA) to: 1, control rats; 2, rats treated with C C 4 and 3, rats intoxicated with C C 4 and also pretreated with colchicine for 7 days. The following enzymatic activities were determined: liver and plasma ASA-esterase, liver UDP-glucuronyltransferase and liver aniline hydroxylase. The time course of plasma concentration of salicylates in similar groups were followed after the intraperitoneal administration of acetylsalicylic acid (ASA), salicylic acid (SA) or gentisic acid (GA). The animals acutely intoxicated with CC14 showed a reduction in urinary excretion of glucuronates and an increased urinary excretion of gentisic and salicylic acids. The activities of plasma and liver ASA-esterases were significantly increased in CCl4-treated rats while the aniline hydroxylase was reduced and the UDP-glucuronyltransferase remained unchanged. The plasma half lives of salicylates were reduced in CClrtreated rats regardless of the administered parent compound. Colchicine pre-treatment completely prevented the alterations produced by acute intoxication with CCI4. The heterogeneity of liver metabolic disfunctions present in acute liver damage was evidenced. It is emphasized that the pharmacokinetic alterations produced by acute liver injury can be the result of complex factors that may involve changes in circulation, hepatic binding protein and other routes of elimination.


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