Protection of human upper respiratory tract cell lines against sulphur mustard toxicity by glutathione esters

被引:11
作者
Andrew, DJ [1 ]
Lindsay, CD [1 ]
机构
[1] DERA, CBD Porton Down, Salisbury SP4 0JQ, Wilts, England
关键词
sulphur mustard; upper respiratory tract; glutathione esters; cell lines;
D O I
10.1191/096032798678908936
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 [卫生毒理学];
摘要
1 Human and animal lung cells have been used successfully to model the toxic effects of inhaled sulphur mustard (HD). The epithelia of the upper respiratory tract are, however, the primary targets of inhaled HD. The aim of this study was to assess the potential of the mono- and di-isopropyl esters of glutathione (MIPE and DIPE respectively) as cytoprotectants in the human upper respiratory tract cell lines BEAS-2B and RPMI 2650. 2 The optimal concentrations for cytoprotection were shown to be 1.0 mg/ml for both DIPE and MIPE. Both compounds were found to protect cells by pretreatment, slightly less protection was observed in cells simultaneously exposed to sulphur mustard. The greatest protection was shown where MIPE or DIPE were in in situ at the time of exposure to HD. The optimum pre-treatment times were found to be 1 h for MIPE and 2 h for DIPE. Limited protection of cells treated with MIPE or DIPE immediately following HD exposure was also demonstrated. No protection was observed if MIPE or DIPE were not administered immediately following HD exposure. 3 Results suggest that MIPE and DIPE may be effective treatments for exposure to HD by inhalation.
引用
收藏
页码:387 / 395
页数:9
相关论文
共 28 条
[1]
EXPRESSION AND MODULATION OF ADHESION MOLECULES ON HUMAN BRONCHIAL EPITHELIAL-CELLS [J].
BLOEMEN, PGM ;
VANDENTWEEL, MC ;
HENRICKS, PAJ ;
ENGELS, F ;
WAGENAAR, SS ;
RUTTEN, AAJJL ;
NIJKAMP, FP .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 1993, 9 (06) :586-593
[2]
TOXICITY DETERMINED INVITRO BY MORPHOLOGICAL ALTERATIONS AND NEUTRAL RED ABSORPTION [J].
BORENFREUND, E ;
PUERNER, JA .
TOXICOLOGY LETTERS, 1985, 24 (2-3) :119-124
[3]
PROTECTIVE ROLE OF ENDOGENOUS PULMONARY GLUTATHIONE AND OTHER SULFHYDRYL COMPOUNDS AGAINST LUNG DAMAGE BY ALKYLATING-AGENTS - INVESTIGATIONS WITH 4-IPOMEANOL IN THE RAT [J].
BOYD, MR ;
STIKO, A ;
STATHAM, CN ;
JONES, RB .
BIOCHEMICAL PHARMACOLOGY, 1982, 31 (08) :1579-1583
[4]
ACUTE AND CHRONIC RESPIRATORY EFFECTS OF SULFUR MUSTARD INTOXICATION IN GUINEA-PIG [J].
CALVET, JH ;
JARREAU, PH ;
LEVAME, M ;
DORTHO, MP ;
LORINO, H ;
HARF, A ;
MACQUINMAVIER, I .
JOURNAL OF APPLIED PHYSIOLOGY, 1994, 76 (02) :681-688
[5]
CHEVILLARD M, 1992, CELL BIOL TOXICOL, V8, P171
[6]
Dacre JC, 1996, PHARMACOL REV, V48, P289
[7]
INVITRO MODELS OF LUNG TOXICITY [J].
FISHER, GL ;
PLACKE, ME .
TOXICOLOGY, 1987, 47 (1-2) :71-93
[8]
DETERMINATION OF CELL NUMBER IN MONOLAYER-CULTURES [J].
GILLIES, RJ ;
DIDIER, N ;
DENTON, M .
ANALYTICAL BIOCHEMISTRY, 1986, 159 (01) :109-113
[9]
BIOCHEMICAL MANIPULATION OF INTRACELLULAR GLUTATHIONE LEVELS INFLUENCES CYTOTOXICITY TO ISOLATED HUMAN-LYMPHOCYTES BY SULFUR MUSTARD [J].
GROSS, CL ;
INNACE, JK ;
HOVATTER, RC ;
MEIER, HL ;
SMITH, WJ .
CELL BIOLOGY AND TOXICOLOGY, 1993, 9 (03) :259-267
[10]
EARLY CYTOTOXIC EFFECTS INDUCED BY BIS-CHLOROETHYL SULFIDE (SULFUR MUSTARD) - [CA(2+)](I) RISE AND TIME-DEPENDENT INHIBITION OF B77 FIBROBLAST SERUM RESPONSE [J].
HUA, A ;
DANIEL, R ;
JASSERON, MP ;
THIRIOT, C .
JOURNAL OF APPLIED TOXICOLOGY, 1993, 13 (03) :161-168