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Titolo:
In vitro absorption and metabolism of a citrus chemopreventive agent, auraptene, and its modifying effects on xenobiotic enzyme activities in mouse livers
Autore:
Murakami, A; Wada, K; Ueda, N; Sasaki, K; Haga, M; Kuki, W; Takahashi, Y; Yonei, H; Koshimizu, K; Ohigashi, H;
Indirizzi:
Kyoto Univ, Grad Sch Agr, Div Appl Life Sci, Kyoto 6068502, Japan Kyoto Univ Kyoto Japan 6068502 , Div Appl Life Sci, Kyoto 6068502, Japan Kinki Univ, Fac Biol Oriented Sci & Technol, Dept Biotechnol Sci, Wakayama6496493, Japan Kinki Univ Wakayama Japan 6496493 Biotechnol Sci, Wakayama6496493, Japan Hlth Sci Univ Hokkaido, Fac Pharmaceut Sci, Ishikari, Hokkaido 0610293, Japan Hlth Sci Univ Hokkaido Ishikari Hokkaido Japan 0610293 ido 0610293, Japan Wakayama Agr Proc Res Corp, Div Res & Dev, Wakayama 6496112, Japan Wakayama Agr Proc Res Corp Wakayama Japan 6496112 akayama 6496112, Japan
Titolo Testata:
NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL
fascicolo: 2, volume: 36, anno: 2000,
pagine: 191 - 199
SICI:
0163-5581(2000)36:2<191:IVAAMO>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
EPITHELIAL CACO-2 CELLS; LIPID-PEROXIDATION; CYTOCHROME-P450 2A6; HUMAN PLASMA; RAT PLASMA; RED WINE; CANCER; COUMARIN; 7-ETHOXYCOUMARIN; CARCINOGENESIS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
37
Recensione:
Indirizzi per estratti:
Indirizzo: Ohigashi, H Kyoto Univ, Grad Sch Agr, Div Appl Life Sci, Kyoto 6068502, Japan Kyoto Univ Kyoto Japan 6068502 ife Sci, Kyoto 6068502, Japan
Citazione:
A. Murakami et al., "In vitro absorption and metabolism of a citrus chemopreventive agent, auraptene, and its modifying effects on xenobiotic enzyme activities in mouse livers", NUTR CANCER, 36(2), 2000, pp. 191-199

Abstract

We previously reported that auraptene (7-geranyloxycoumarin, AUR), widely occurring in citrus fruit, is a structurally novel type of effective cancer-preventive agent, as manifested in several rodent models. However, its bioavailability and metabolism in biological systems have yet to be investigated. In the present study, we examined the chemical stability of AUR at pH 1.57 and 37 degrees C (as a stomach digestion model) and observed its stoichiometric conversion to umbelliferone [7-hydroxycoumarin, UMB; half-life (t(1/2)) = 15 h; 7-ethoxycoumarin (ETC) was stable for 24 h]. Differentiated Caco-2 cells, a human colorectal adenocarcinoma cell line, were used as a small intestine model. ETC permeated the basolateral (portal vein) side of Caco-2 cells in a time-dependent manner; AUR slightly permeated the cells, but with an intracellular accumulation. Epoxyauraptene and UMB were detected when AUR was treated with the rat liver S-9 mixture. ETC was also convertedto UMB, but its t(1/2) of two hours was much shorter than that of AUR (>24h). This suggests that AUR, bearing a geranyloxyl side chain, is a relatively metabolism-resistant substrate for cytochrome P-450 enzymes and, thus, is stable in the liver compared with ETC. Oral administration of AUR by gavage at 50-200 mg/kg body wt dose dependently induced glutathione S-transferase (GST) activity in mouse livers without affecting cytochrome P-450 activity. Using 10 coumarin-related compounds, we found that only those coumarins having a 7-alkyloxyl group induced GST, but not cytochrome P-450, activity. The present study presumes that AUR accumulates in the epithelial cells of the small intestine and then gradually permeates into the portal vein. Stable localizability of AUR in the colon and fiver may be associated with the induction of GST activity, which is important as the action mechanism for suppression of rodent chemical carcinogenesis.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/01/20 alle ore 00:42:31