Indomethacin attenuation of hepatic perfusion and plasma 6-ketoPGF1 alpha elevations following glutathione depletion in rabbits.
Glutathione (GSH) is important in detoxification and regulating cyclooxygenase activity. Since the liver has high levels of GSH, xenobiotic-induced changes in hepatic GSH could affect hepatic tissue blood perfusion (HP) via alterations in prostaglandin synthesis. In anesthetized male New Zealand rabbits, elevating GSH with GSH monoethyl ester had no affect on HP. Treatment of rabbits with diethyl maleate to deplete GSH also had no affect on HP in animals previously given GSH monoethyl ester. However, HP increased within 20 min in rabbits treated with diethyl maleate prior to GSH monoethyl ester. In another experiment, a similar rise in HP following GSH depletion was accompanied by arterial plasma 6-ketoPGF1 alpha (the stable metabolite of prostacyclin) levels that were 4-times higher than in the controls. Plasma TxB2 (the stable metabolite of thromboxane) also increased following diethyl maleate, but only to levels that were 25-times lower than for 6-ketoPGF1 alpha. Since indomethacin blocked the rise in HP, as well as the increases in 6-ketoPGF1 alpha and TxB2, these results indicate changes in HP may occur following GSH depletion as a result of increased synthesis of one or more arachidonic acid metabolites and implicate prostacyclin as a possible mediator of this phenomenon.
Bottje
W
W
Department of Animal and Poultry Sciences, University of Arkansas, Fayetteville 72701.
Glahn
R
R
Beers
K
K
Nejad
H
H
Graupner
W
W
Holmes
K R
KR
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood*; D000136:Acid-Base Equilibrium / Q000187:drug effects; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism*; D008102:Liver Circulation / Q000187:drug effects*; D008297:Male; D008298:Maleates / Q000494:pharmacology; D011817:Rabbits; D013929:Thromboxane B2 / Q000097:blood
D008298:Maleates; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; C014476:diethyl maleate; D005978:Glutathione; D007213:Indomethacin