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A sensitive method for determining the nephrotoxic effects of the analgesic acetaminophen upon esterases using isoelectric focusing
Author(s) -
Hennis Hugh L.,
Allen Robert C.,
Hennigar Gordon R.,
Simmons Margaret A.
Publication year - 1981
Publication title -
electrophoresis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.666
H-Index - 158
eISSN - 1522-2683
pISSN - 0173-0835
DOI - 10.1002/elps.1150020311
Subject(s) - nephrotoxicity , kidney , acetaminophen , isoelectric focusing , toxicity , isoelectric point , analgesic , biology , chemistry , pharmacology , enzyme , biochemistry , endocrinology , medicine
In a study of the biochemical mechanisms of renal toxicity of acetaminophen, quantitative studies of the nonspecific kidney esterases were carried out in New Zealand white female rabbits. After the administration of a sublethal dose of 2.5 g/kg acetaminophen, four animals each plus four controls were sacrificed at 24 and 48 h. subsequent isoelectric focusing of kidney homogenate supernatants over a pH range of 3.5–8.0 showed marked changes in each of the groups. Zymograms of the nonspecific esterases in each group showed a characteristic pattern which deviated greatly from control animals. A morphological and histochemical examination of kidney sections from all animals showed no pathological changes in any of the kidneys. This would indicate that abnormal biochemical changes are being manifested in the kidney long before any morphological deviations. It would seem that this group of enzymes could provide a valuable market for early toxicological changes.