The effect of sulphur mustard on glutathione levels in rat lung slices and the influence of treatment with arylthiols and cysteine esters

Abstract

1 Sulphur mustard reacts directly with benzenethiols and cysteine esters in aqueous medium.

2 Benzenethiols diffuse into lung slices in short term culture.

3 Treatment of lung slices in short term culture with benzenethiols does not protect cellular glutathione from conjugation with sulphur mustard.

4 Following uptake of cysteine ester into lung slices cysteine is elevated but this does not protect cellular glutathione from sulphur mustard.

Keywords

sulphur mustard benzenethiol 2,6-dimethoxybenze nethiol cysteine ester lung slice

Get full access to this article

View all access options for this article.

References

Papirmeister B. , Feister AJ , Robinson SI , Ford RD Medical Defence Against Mustard Gas: Mechanisms and Pharmacological Implications . CRC Press: Boston, 1991.

Boyd MR , Statham CN , Jones RB Protective role of endogenous pulmonary glutathione and other sulphydryl compounds against lung damage by alkylating agents. Biochemical Pharmacology 1982; 31: 1579-83.

Black RM et al. Biological fate of sulphur mustard, 1,1'-thiobis (2-chloroethane): isolation and identification of urinary metabolites following intraperitoneal administration to rat. Xenobiotica 1992; 22: 405-18.

Hobbs MJ , Butterworth M. , Cohen GM , Upshall DG Structure activity relationships of cysteine esters and their effects on thiol levels in rat lung in vitro. Biochemical Pharmacology 1993; 45: 1605 - 12.

Lailey AF , Lawston IW , Stanton D. , Upshall DG Protection by cysteine esters against chemically induced pulmonary oedema . Biochemical Pharmacology 1991; 42: S45-S54.

Timperley CM et al. Reactions of methoxyarylthiols with styrene-7,8-oxide and perfluoroisobutene: Towards the development of therapeutic nucleophiles. (in preparation) 1996.

Langford AM et al. The effects of electrophiles on glutathione levels in liver and lung in vitro and the possible protective effects of exogenous thiols . Human and Experimental Toxicology 1994; 13: 294.

Price RJ et al. Toxicity of 3 methylindole, 1-nitronaphthalene and paraquat in precision cut lung slices. Archives of Toxicology 1995; 69: 405-9.

Leo A. , Hansch C. , Elkins D. Partition coefficients and their uses. Chemical Reviews 1971; 71: 525-615.

10.

Potter DW , Tran TB Apparent rates of glutathione turnover in rat tissues. Toxicology and Applied Pharmacology 1993; 120: 186-92.

11.

Deneke SM , Fanburg BL Regulations of cellular glutathione. American Journal of Physiology 1989; 257: L163 - L173.

12.

Maisonneuve A. , Callebat I. , Deborde L. , Coppet L. Biological fate of sulphur mustard in rat: toxicokinetics and disposition. Xenobiotica 1993; 23: 771-80.

13.

Wilde PE , Upshall DG Cysteine esters protect cultured rodent lung slices from sulphur mustard . Human and Experimental Toxicology 1994; 13: 743-8.

14.

Sawyer TW , Wilde PE , Rice P. , Weiss MT Toxicity of sulphur mustard in adult rat lung organ culture. Toxicology 1995; 100: 39-49.

15.

Lailey AF , Upshall DG Thiol levels in rat bronchio-alveolar lavage fluid after administration of cysteine esters. Human and Experimental Toxicology 1994; 13: 776-81.

16.

Cantin AM , North SL , Hubbard RC , Crystal RG Normal alveolar epithelial lining fluid contains high levels of glutathione . Journal of Applied Physiology 1987; 63: 152-7.