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In vitro inactivation of plasma alpha1-proteinase inhibitor by epoxides and 1,2-dihaloethanes.

Authors
Ansari-GA; Gan-JC; Barton-BK
Source
Arch Environ Contam Toxicol 1988 Jul; 17(4):537-542
NIOSHTIC No.
00180348
Abstract
The inactivation of alpha1-proteinase inhibitor (a1PI) by epoxides and 1,2-dihaloethanes was studied in-vitro. a1PI and whole plasma were incubated with styrene-oxide (96093), ethylene-oxide (75218), propylene-oxide (75569), 1,2-dichloroethane (107062) (DECE), or 1,2- dibromoethane (106934) (DBE) for 2 hours. The effects on elastase inhibiting capacity (EIC) and trypsin inhibiting capacity (TIC) were examined. The extent of alkylation of amino groups on a1PI by the compounds was determined. The epoxides reduced the EIC and TIC of a1PI and plasma. Styrene-oxide was the most effective inhibitor, followed by ethylene-oxide and propylene-oxide in that order. Styrene-oxide modified four amino groups on a1PI. DCE and DBE reduced the EIC and TIC of a1PI, but to a lesser extent than that produced by the epoxides. DCE was more effective than DBE. The concentrations required for inhibiting EIC or TIC of whole plasma were generally higher than those required for inactivating a1PI. DECE alkylated three amino groups on a1PI and DBE two amino groups. The authors conclude that a1PI in whole plasma is inhibited at higher concentrations than pure a1PI. It is considered unlikely that humans will be exposed to such high concentrations except in the case of accidental acute exposure. Since in-vitro studies do not address the effect of metabolites of the chemicals on the inhibitory activity of a1PI, in-vivo studies are needed.
Keywords
NIOSH-Publication; NIOSH-Grant; Epoxy-compounds; Physiological-chemistry; Blood-plasma; Organo-chlorine-compounds; Organo-bromine-compounds; In-vitro-studies; Dose-response
Contact
Human Biol Chem and Genetics University of Texas Med BR Dept of Human Biol Chem&gene Galveston, Tex 77550-2774
CODEN
AECTCV
CAS No.
96-09-3; 75-21-8; 75-56-9; 107-06-2; 106-93-4
Publication Date
19880701
Document Type
Journal Article
Funding Amount
721590.00
Funding Type
Grant
Fiscal Year
1988
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-02149
Issue of Publication
4
ISSN
0090-4341
Source Name
Archives of Environmental Contamination and Toxicology
State
TX
Performing Organization
University of Texas Medical Branch, Galveston, Texas
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