Structure-Activity Relationships of Cyteine Esters in Rat Lung Slices and Bronchiolar-Alveolar Lavage Fluid in Vivo.
Abstract
Pretreatment with cysteine esters increases cysteine (CySH) levels in the rat lung and protects against the lethal effects of inhaled perfluoroisobutene (PFIB) in vivo. In this study we have compared the uptake and metabolism of N-acetyl cysteine (NAc), CySH, cysteine esters and cystine esters in vitro using rat lung and liver homogenates and lung slices and determined the levels of CySH and glutathione (GSH) in the bronchioalveolar lavage fluid (BAL) of rats following ip injection of NAc or esters of CySH. Liver homogenates metabolished CySh and cysteine esters faster than-lung homogenates. (t1/2 CySH: lung: 58.8 + or = 17.3 min, liver: 14.0 + or = 1.6 min; t1/2 esters: lung were between 6.5 - 12.1 min, liver 1.9 5.3 min). Cysteine t-butyl ester (CTBE), which does not protect in vivo, was not hydrolysed to CySH by lung or liver homogenates. All esters increased and prolonged intracellular CySH concentrations in lung slices to a much greater extent than CySH itself. In lung slices CySH elevated intracellular CySH to between 0.22 + or - 0.03 to 1.24 + or - 0.07 nmol/mg wet wt. The most effective of the cysteine esters was cysteine cyclohexyl ester (CCHE) which increased CySH to a maximum of 4.57 + or 0.17 nmol/mg wet wt at 45 min and remained elevated at 60 min (4.13 + or - 0.37 nmol/mg wet wt), but with cysteine methyl ester (CME) the least effective ester, CySH levels peaked at 10 min (2.60 +/- 0.5 nmol/mg wet wt) but had decreased to 1.25 +/- 0.08 nmol/mg wet wt by 60 min. CCHE prolonged the increase of CySH the longest and CME the shortest. Cystine esters increased intracellular concentrations of both cystine and CySH.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 13, 1993
- Accession Number
- ADP008876
Entities
People
- Alison F. Lailey
- David G. Upshaw
- Michael J. Hobbs