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Aspirin disposition in rats acutely intoxicated with CCl 4
Author(s) -
Favari Liliana,
Mourelle Marisabel,
Amezcua Joseg Luis
Publication year - 1987
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.2550070603
Subject(s) - gentisic acid , salicylic acid , chemistry , aspirin , pharmacology , colchicine , toxicokinetics , excretion , pharmacokinetics , liver injury , phospholipidosis , endocrinology , medicine , metabolism , biochemistry , phospholipid , membrane
The profile of urinary salicylate metabolites was determined after an oral administration of acetylsalicylic acid (ASA) to: 1, control rats; 2, rats treated with CCl 4 and 3, rats intoxicated with CCl 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 CCl 4 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 CCl 4 ‐treated rats while the aniline hydroxylase was reduced and the UDP‐glucuronyltransferase remained unchanged. The plasma half lives of salicylates were reduced in CCl 4 ‐treated rats regardless of the administered parent compound. Colchicine pre‐treatment completely prevented the alterations produced by acute intoxication with CCl 4 . 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.