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Titolo:
DISTRIBUTION OF MENAQUINONE-4, A THERAPEUTIC AGENT FOR OSTEOPOROSIS, IN BONE AND OTHER TISSUES OF RATS
Autore:
SANO Y; TADANO K; KANEKO K; KIKUCHI K; YUZURIHA T;
Indirizzi:
EISAI & CO LTD,TSUKUBA RES LABS TSUKUBA IBARAKI 30026 JAPAN
Titolo Testata:
Journal of nutritional science and vitaminology
fascicolo: 5, volume: 41, anno: 1995,
pagine: 499 - 514
SICI:
0301-4800(1995)41:5<499:DOMATA>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
GAMMA-CARBOXYGLUTAMIC ACID; VITAMIN-K METABOLISM; IDENTIFICATION; PROTHROMBIN; MICROSOMES; RESIDUES; KIDNEY;
Keywords:
MENAQUINONE-4; VITAMIN-K; ORAL; BONE; DISTRIBUTION; OVARIECTOMY; RATS; RADIOACTIVITY; MICROAUTORADIOGRAPHY; OSTEOPOROSIS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
20
Recensione:
Indirizzi per estratti:
Citazione:
Y. Sano et al., "DISTRIBUTION OF MENAQUINONE-4, A THERAPEUTIC AGENT FOR OSTEOPOROSIS, IN BONE AND OTHER TISSUES OF RATS", Journal of nutritional science and vitaminology, 41(5), 1995, pp. 499-514

Abstract

[C-14] Menaquinone-4 was administered orally once daily at a dose of 4 mg/kg for ten days to female rats of different ages to determine itsblood and tissue distribution with particular attention to its distribution in bone. Animals aged 10 and 30 months were either ovariectomized or sham-operated as a control, and young rats aged 7 weeks were used as untreated controls. Blood concentrations of radioactivity at 24 hafter each dose during repeated administration increased daily and approached a steady state by the seventh dose. Higher concentrations of radioactivity in blood (plasma) were observed in older animals than inthe younger ones, but there was little difference between ovariectomized rats (OVX rats) and sham-operated rats (Sham rats). In tissue samples collected at 1.5 h after administration, the liver, adipose tissue, spleen and adrenals showed higher concentrations of radioactivity than the other organs and the plasma. In bone tissues, the bone marrow (BM) and cancellous tissue (CT) of the femur showed radioactivity concentrations which were higher than that in the plasma, and these increased during repeated administration. Finally, at 24 h after the last dose, the concentrations of radioactivity in bone tissues of older animals (BM, 5,807.2 ng eq/g; CT, 5,264.8 ng eq/g in OVX rats aged 10 monthsand BM, 11,479.3 ng eq/g; CT, 4,023.0 ng eq/g in OVX rats aged 30 months) were several times higher than those in younger animals (BM, 2,771.6 ng eq/g; CT, 890.2 ng eq/g in 7-week-old untreated rats). The values in OVX rats were also higher than those in Sham rats. Furthermore, micro autoradiography studies of femur sections from OVX rats indicated that [C-14]Menaquinone-4 localized in cancellous tissue where bone is known to be actively remodelled. The concentrations of radioactivityin cancellous tissue and bone marrow of OVX rats aged 10 and 30 months were comparable to the pharmacologically effective concentrations ofMenaquinone-4 (10(-6)-10(-5) M) in in vitro studies on bone formation. These findings suggest that orally administered Menaquinone-4 distributes specifically into the bone tissues of ovariectomized rats and this is consistent with its effect as a therapeutic agent for osteoporosis.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/01/20 alle ore 14:02:19