Abstract
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.
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