Biomaterial Database

Covalent binding of metabolites of acetaminophen to kidney protein and depletion of renal glutathione. 1978

G H Mudge, and M W Gemborys, and G G Duggin

Experiments in CD-1 mice and Sprague-Dawley rats were carried out to determine the extent to which biochemical changes described previously for acute acetaminophen-induced hepatotoxicity might be applicable to the kidney. After intraperitoneal injection of acetaminophen, tissue glutathione and covalent binding of tritiated metabolites of acetaminophen to tissue protein were measured for liver, kidney cortex and kidney papilla. Glutathione was reduced more in mice than in rats, and more in liver than in kidney, without appearance of oxidized glutathione in either tissue. Covalent binding was likewise greater in mice than in rats and greater in liver than in kidney. The determination of covalent binding was extremely sensitive to the trace radiochemical impurities of the labeled drug. With prior administration of 3-methyl-cholanthrene, the induced changes were far greater in liver than in kidney, suggesting that the formation of a reactive metabolite from acetaminophen occurred in each organ by slightly different mechanisms. At doses less than those associated with demonstrable acute toxicity, the duration of covalent binding to protein was longer for renal papilla than for renal cortex or for liver. The results may be applicable to the pathogenesis of both acute and chronic nephrotoxicity.

UI	MeSH Term	Description	Entries
D007668	Kidney	Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.	Kidneys
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D008297	Male		Males
D011485	Protein Binding	The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.	Plasma Protein Binding Capacity,Binding, Protein
D001798	Blood Proteins	Proteins that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins.	Blood Protein,Plasma Protein,Plasma Proteins,Serum Protein,Serum Proteins,Protein, Blood,Protein, Plasma,Protein, Serum,Proteins, Blood,Proteins, Plasma,Proteins, Serum
D004231	Diuresis	An increase in the excretion of URINE. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)	Diureses
D005978	Glutathione	A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.	Reduced Glutathione,gamma-L-Glu-L-Cys-Gly,gamma-L-Glutamyl-L-Cysteinylglycine,Glutathione, Reduced,gamma L Glu L Cys Gly,gamma L Glutamyl L Cysteinylglycine
D000082	Acetaminophen	Analgesic antipyretic derivative of acetanilide. It has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage.	Acetamidophenol,Hydroxyacetanilide,Paracetamol,APAP,Acamol,Acephen,Acetaco,Acetominophen,Algotropyl,Anacin-3,Datril,N-(4-Hydroxyphenyl)acetanilide,N-Acetyl-p-aminophenol,Panadol,Tylenol,p-Acetamidophenol,p-Hydroxyacetanilide,Anacin 3,Anacin3
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013997	Time Factors	Elements of limited time intervals, contributing to particular results or situations.	Time Series,Factor, Time,Time Factor