Effect of glutathione depletion on tissue and plasma prostacyclin and thromboxane in rats.
Experiments were designed to determine the effects of glutathione (GSH) depletion with L-buthionine sulfoximine (BSO) or diethyl maleate (DEM) on tissue and plasma prostacyclin (6-keto-PGF1 alpha) and thromboxane (TxB2) levels in male Sprague-Dawley rats. Despite depleting hepatic GSH to as much as 34% of control, BSO at various levels (0.4, 0.8 and 1.2 g/kg body wt) had no effect on hepatic, renal, pulmonary or cardiac tissue levels of 6-keto-PGF1 alpha and TxB2 or circulating levels of 6-keto-PGF1 alpha in portal or arterial plasma. When rats were pretreated with 3-methylcholanthrene (3-MC) to induce cytochrome P450, BSO (0.8 g/kg body wt) also had no effect on tissue or plasma prostanoid levels with the exception of a slight, but significant, increase in hepatic 6-keto-PGF1 alpha in non-induced rats. In contrast, depletions of hepatic, renal and pulmonary tissue GSH by DEM (1 mL/kg body wt) to 12, 50 and 30% of control, respectively, were associated with elevations of 6-keto-PGF1 alpha in these tissues and in plasma obtained by right ventricular heart puncture. Pretreatment of rats with 3-MC had no significant effect on tissue GSH or prostanoid levels in controls or DEM-treated rats but plasma levels of 6-keto-PGF1 alpha were lower in comparison to non-induced rats. DEM with or without 3-MC pretreatment was associated with increased TxB2 in renal tissue, whereas DEM elevated TxB2 only in pulmonary tissue from non-induced rats. It appears that factors besides GSH depletion may be required to raise plasma and/or tissue 6-keto-PGF1 alpha levels in vivo.
Maynard
P M
PM
Department of Animal and Poultry Sciences, University of Arkansas, Fayetteville 72701.
Graupner
W G
WG
Bottje
W G
WG
D000818:Animals; D019328:Buthionine Sulfoximine; D011464:Epoprostenol / Q000097:blood / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008298:Maleates / Q000494:pharmacology; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D008748:Methylcholanthrene; D051381:Rats; D011919:Rats, Inbred Strains; D013929:Thromboxane B2 / Q000097:blood / Q000378:metabolism*
D008298:Maleates; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D013929:Thromboxane B2; D008748:Methylcholanthrene; D011464:Epoprostenol; C014476:diethyl maleate; D005978:Glutathione