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Title: OBSERVATIONS ON THE TANGERETIN METABOLITES IN HAMSTER

Author
item Manthey, John
item KUROWSKA, ELA - KGK SYNERGIZE, ONTARIO

Submitted to: Subtropical Technology Conference Proceedings
Publication Type: Abstract Only
Publication Acceptance Date: 9/16/2003
Publication Date: 10/16/2003
Citation: Manthey, J.A., Kurowska, E. 2003. Observations on the tangeretin metabolites in hamster. Subtropical Technology Conference Proceedings. 54:37-38.

Interpretive Summary:

Technical Abstract: Many in vitro studies have demonstrated that citrus polymethoxylated flavones have biological activities that are possibly coupled to the prevention of cancer, inflammation, and certain other chronic diseases. Studies addressing the metabolism and tissue accumulation of these compounds in animals have provided insights into the potential roles of these compounds in disease prevention. Previous studies of the metabolism of tangeretin in rats showed the occurrence of a collection of metabolites with intact ring systems. This indicated that tangeretin, and supposedly all the other polymethoxylated flavones, are metabolized differently than common hydroxylated flavonoids which are mainly metabolized by ring scission leading to various phenylacetic and phenylpropionic acid derivatives. In our recent feeding trials with hamsters, numerous metabolites of tangeretin in the serum, urine and liver were detected by HPLC-MS. The metabolites that were detected in the serum and urine consisted mainly of glucuronides, with aglycones only present at trace levels. The glucuronides occurred mainly as dihydroxy-trimethoxyflavones and monohydroxy-tetramethoxyflavones. No evidence was seen in these initial studies of sulfate derivatives, nor were there any indications of diglucuronidated flavones. In contrast to the serum and urine samples, LC-MS analysis of the liver extracts showed a preponderance of aglycones over the glucuronides. Trace levels of intact tangeretin were also detected in the liver. The similarities in the UV spectra of the metabolites to the spectrum of tangeretin allowed the use of mass-corrected conversion factors derived from the value for tangeretin to estimate the levels of these metabolites in the different hamster tissues. Total levels of metabolites in the liver extracts ranged from 29 ppm to 115 ppm. High levels of tangeretin metabolites were also detected in the urine and serum. These high concentrations of tangeretin metabolites suggest that sufficiently high levels of these compounds may occur to allow the expression of biological activities in vivo. In a parallel feeding study involving a mixture of tangeretin and nobiletin (9/1), additional metabolites putatively derived from nobiletin were detected. Evidence points to the metabolism of nobiletin similar to tangeretin.