PROSTACYCLIN ELEVATION FOLLOWING GLUTATHIONE DEPLETION IN-VIVO - POSSIBLE THRESHOLD DEPENDENCY IN LIVER AND LUNG

Citation
Wg. Bottje et al., PROSTACYCLIN ELEVATION FOLLOWING GLUTATHIONE DEPLETION IN-VIVO - POSSIBLE THRESHOLD DEPENDENCY IN LIVER AND LUNG, Biochemical pharmacology, 46(6), 1993, pp. 1019-1027
Citations number
44
Categorie Soggetti
Pharmacology & Pharmacy",Biology
Journal title
ISSN journal
00062952
Volume
46
Issue
6
Year of publication
1993
Pages
1019 - 1027
Database
ISI
SICI code
0006-2952(1993)46:6<1019:PEFGDI>2.0.ZU;2-J
Abstract
The major objective of this study was to determine if a threshold leve l of glutathione (GSH) depletion is required to elevate plasma prostac yclin (6-ketoPGF1alpha) in male Sprague-Dawley rats. Rats were treated i.p. with various doses of phorone, diethyl maleate (DEM), or GSH wit h and without DEM. Similar maximal depletions of hepatic GSH (to 10% o f control) and renal GSH (to 50% of control) were observed with DEM an d phorone, but lung GSH was depleted maximally by only 30% with phoron e compared with a 70% depletion by DEM. Changes in lung GSH, but not k idney GSH, were closely correlated with changes in hepatic GSH. 6-Keto PGF1alpha levels in the lung were 10- to 30-fold higher than in kidney or liver, and there was a stronger correlation between lung and plasm a 6-ketoPGF1alpha than with the other two tissues. The increase in lun g 6-ketoPGF1alpha following GSH depletion did not appear to be due to a shift in prostaglandin metabolite synthesis since reciprocal changes in PGE, were not observed; lung PGE, levels were largely unaffected b y DEM or phorone. Both DEM and phorone elevated plasma 6-ketoPGF1alpha but the magnitude of increase for DEM (5- to 6-fold) was much greater than the 2-fold increase for phorone. The increase in plasma 6-ketoPG F1alpha by 1.0 mL DEM/kg was attenuated by simultaneous administration of 2 mmol GSH/kg. The results indicate that the lung may he responsib le for increases in plasma 6-ketoPGF1alpha following GSH depletion and that a critical level of GSH depletion in the liver and/or lung may b e necessary to elevate plasma 6-ketoPGF1alpha levels.