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Titolo:
Spatial glutathione and cysteine distribution and chemical modulation in the early organogenesis-stage rat conceptus in utero
Autore:
Beck, MJ; McLellan, C; Lightle, RLF; Philbert, MA; Harris, C;
Indirizzi:
Univ Michigan, Toxicol Program, Dept Environm Hlth Sci, Sch Publ Hlth 2, Ann Arbor, MI 48109 USA Univ Michigan Ann Arbor MI USA 48109 Publ Hlth 2, Ann Arbor, MI 48109 USA NSF Int, Dept Toxicol, Ann Arbor, MI 48105 USA NSF Int Ann Arbor MI USA 48105 Int, Dept Toxicol, Ann Arbor, MI 48105 USA
Titolo Testata:
TOXICOLOGICAL SCIENCES
fascicolo: 1, volume: 62, anno: 2001,
pagine: 92 - 102
SICI:
1096-6080(200107)62:1<92:SGACDA>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
INDUCED HEPATIC NECROSIS; PHENYTOIN TERATOGENICITY; BUTHIONINE SULFOXIMINE; CATALYZED BIOACTIVATION; OXIDIZED GLUTATHIONE; TRANSPORT ACTIVITY; HUMAN-FIBROBLASTS; OXIDATIVE STRESS; COVALENT BINDING; EMBRYO CULTURE;
Keywords:
glutathione; cysteine; embryo; VYS; acetaminophen; mercury orange; in utero;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
70
Recensione:
Indirizzi per estratti:
Indirizzo: Harris, C Univ Michigan, Toxicol Program, Dept Environm Hlth Sci, Sch PublHlth 2, M6116,1420 Washington Hts, Ann Arbor, MI 48109 USA Univ Michigan M6116,1420 Washington Hts Ann Arbor MI USA 48109 A
Citazione:
M.J. Beck et al., "Spatial glutathione and cysteine distribution and chemical modulation in the early organogenesis-stage rat conceptus in utero", TOXICOL SCI, 62(1), 2001, pp. 92-102

Abstract

Glutathione (GSH), cysteine, and other low-molecular-weight thiols (LMWT) play a vital role in the detoxication of xenobiotics and endogenous chemicals. Differential alterations of LMWT status in various cell types of the developing embryo may underlie cell-specific sensitivity or resistance to xenobiotics and contribute to embryotoxicity. This study describes the spatialand temporal distribution of LMWTs in rat conceptuses and alterations produced by the non-teratogenic GSH modulator, acetaminophen (APAP). Pregnant female rats were given 125, 250, or 500 mg/kg APAP (po) on gestational day 9. Conceptal LMWT was localized histochemically using mercury orange in cryosections, and GSH and cysteine concentrations were measured by HPLC analysis. Mercury orange histofluorescence revealed a non-uniform distribution of LMWT in untreated conceptal tissues, with strongest staining observed in the ectoplacental cone (EPC), visceral yolk sac (VYS), and embryonic heart. Less intense staining was observed in the neuroepithelium. Following treatment with APAP, tissue-associated LMWT decreased dramatically except in the EPC, while exocoelomic fluid LMWT, and LMWT within embryonic lumens, increased. Exposure to 250 mg/kg APAP decreased embryonic GSH after 6 and 24 h by 46% and 38%, respectively. Acetaminophen (500 mg/kg) decreased embryonic and VYS cysteine content by 54% and 83%, respectively, after 24 h. Acetaminophen alters the spatial distribution of LMWT in rat conceptuses, particularly with respect to cysteine. The mobilization of cysteine following chemicalinsult may influence the ability of conceptal cells to maintain normal GSHstatus due to reduced availability of cysteine for de novo GSH synthesis.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 23/09/20 alle ore 05:55:42