Metabolism and disposition of juglone in male F344 rats.
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.
Chen
L-J
LJ
Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. ferguso2@niehs.nih.gov
Lebetkin
E H
EH
Burka
L T
LT
D000284:Administration, Oral; D000287:Administration, Topical; D000818:Animals; D005243:Feces / Q000737:chemistry*; D007275:Injections, Intravenous; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D009285:Naphthoquinones / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D009928:Organ Specificity; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution
D009285:Naphthoquinones; C005134:juglone