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Titolo:
Chronic vascular toxicity of doxorubicin in an organ-cultured artery
Autore:
Murata, T; Yamawaki, H; Hori, M; Sato, K; Ozaki, H; Karaki, H;
Indirizzi:
Univ Tokyo, Grad Sch Agr & Life Sci, Dept Vet Pharmacol, Bunkyo Ku, Tokyo 1138657, Japan Univ Tokyo Tokyo Japan 1138657 harmacol, Bunkyo Ku, Tokyo 1138657, Japan
Titolo Testata:
BRITISH JOURNAL OF PHARMACOLOGY
fascicolo: 7, volume: 132, anno: 2001,
pagine: 1365 - 1373
SICI:
0007-1188(200104)132:7<1365:CVTODI>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
CELL LUNG-CANCER; INDUCED APOPTOSIS; SMOOTH-MUSCLE; INDUCED CARDIOMYOPATHY; IN-VIVO; HEART; INHIBITION; RESISTANCE; CISPLATIN; MECHANISM;
Keywords:
doxorubicin; rabbit mesenteric artery; apoptosis; alpha(1A)-adrenoceptor; smooth muscle contractility;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
29
Recensione:
Indirizzi per estratti:
Indirizzo: Ozaki, H Univ Tokyo, Grad Sch Agr & Life Sci, Dept Vet Pharmacol, Bunkyo Ku, Yayoi 1-1-1, Tokyo 1138657, Japan Univ Tokyo Yayoi 1-1-1 Tokyo Japan 1138657 Tokyo 1138657, Japan
Citazione:
T. Murata et al., "Chronic vascular toxicity of doxorubicin in an organ-cultured artery", BR J PHARM, 132(7), 2001, pp. 1365-1373

Abstract

1 We investigated the chronic effects of doxorubicin (DXR) on morphological and functional changes in the rabbit mesenteric artery using an organ culture system.2 In arteries cultured with 0.3 muM DXR for 7 days, the contractions induced by noradrenaline, but not those induced by endothelin-l or high K+, werestrongly inhibited. This reaction was followed by a decrease in the induction of the alpha (1A)-adrenoceptor without any change in the mRNA level. Inhibition of noradrenaline-induced contractions by DXR was attenuated by superoxide dismutase, and alpha (1A)-adrenoceptor protein expression recovered.3 In the arteries cultured with 1 muM DXR for 7 days, contractions inducedby endothelin-l or high K+ and absolute force in the permeabilized muscleswere also inhibited. Morphological examinations revealed the existence of concentrated nuclei and terminal deoxynucleotidyl transferase-mediated dUTPnick-end labelling (TUNEL)-positive smooth muscle cells, and internucleosomal DNA fragmentation was also detected, indicating the induction of apoptosis.4 In the arteries cultured with 10 muM DXR for 7 days, nuclear swelling, karyolysis and random DNA fragmentation indicative of necrosis were observed, and muscle contractility was abolished.5 These results suggest that 0.3 muM DXR selectively down-regulates the alpha (1A)-adrenoceptor protein expression, resulting in a decrease in the noradrenaline-induced contraction. This down-regulation may be at least partly due to the production of a superoxide radical. DXR also caused a decreasein muscle contractility followed by apoptotic changes at 1 muM and necrotic changes at 10 muM. These changes might be responsible for the disturbanceof the circulatory system that is often observed during the course of repetitive chemotherapy.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 09/07/20 alle ore 20:55:55