Metabolism and disposition of juglone in male F344 rats. 2005

L-J Chen, and E H Lebetkin, and L T Burka
Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. ferguso2@niehs.nih.gov

The metabolism and disposition of 14C-labelled juglone in male F344 rats following oral, intravenous and dermal administration were studied. Approximately 40-50% of an oral dose (0.1 to 10 mg kg-1) and less than 20% of the dermal dose (4 mg kg-1) were absorbed within 24 h. Most of the oral dose was excreted in faeces and urine within 24 h and only 1-3% remained in the tissues. High concentrations of juglone-derived radioactivity were found in kidney for all three dosing routes. The accumulation in kidney can be attributed to covalent binding of juglone and/or metabolites to cytosolic protein. Five metabolites were identified in the urine of rats treated with an oral dose: 1,4,5-trihydroxynaphthalene di-glucuronide, 1,4,5-trihydroxynaphthalene mono-glucuronide mono-sulfate, 2-sulfo-2,3-dihydrojuglone, 4,8-dihydroxy-1-tetralone mono-glucuronide and 1,4,5-trihydroxynaphthalene mono-glucuronide. Liver microsomal incubations of juglone in the presence of NAD(P)H and UDP-glucuronic acid gave rise to two 1,4,5-trihydroxynaphthalene mono-glucuronides.

UI MeSH Term Description Entries
D007275 Injections, Intravenous Injections made into a vein for therapeutic or experimental purposes. Intravenous Injections,Injection, Intravenous,Intravenous Injection
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
D008657 Metabolic Clearance Rate Volume of biological fluid completely cleared of drug metabolites as measured in unit time. Elimination occurs as a result of metabolic processes in the kidney, liver, saliva, sweat, intestine, heart, brain, or other site. Total Body Clearance Rate,Clearance Rate, Metabolic,Clearance Rates, Metabolic,Metabolic Clearance Rates,Rate, Metabolic Clearance,Rates, Metabolic Clearance
D009285 Naphthoquinones Naphthalene rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups. Naphthalenediones,Naphthazarins,Naphthoquinone
D009928 Organ Specificity Characteristic restricted to a particular organ of the body, such as a cell type, metabolic response or expression of a particular protein or antigen. Tissue Specificity,Organ Specificities,Specificities, Organ,Specificities, Tissue,Specificity, Organ,Specificity, Tissue,Tissue Specificities
D011916 Rats, Inbred F344 An inbred strain of rat that is used for general BIOMEDICAL RESEARCH purposes. Fischer Rats,Rats, Inbred CDF,Rats, Inbred Fischer 344,Rats, F344,Rats, Inbred Fisher 344,CDF Rat, Inbred,CDF Rats, Inbred,F344 Rat,F344 Rat, Inbred,F344 Rats,F344 Rats, Inbred,Inbred CDF Rat,Inbred CDF Rats,Inbred F344 Rat,Inbred F344 Rats,Rat, F344,Rat, Inbred CDF,Rat, Inbred F344,Rats, Fischer
D005243 Feces Excrement from the INTESTINES, containing unabsorbed solids, waste products, secretions, and BACTERIA of the DIGESTIVE SYSTEM.
D000284 Administration, Oral The giving of drugs, chemicals, or other substances by mouth. Drug Administration, Oral,Administration, Oral Drug,Oral Administration,Oral Drug Administration,Administrations, Oral,Administrations, Oral Drug,Drug Administrations, Oral,Oral Administrations,Oral Drug Administrations

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