thromboxane-b2 and diethyl-maleate

1. Effects of diethyl maleate (DEM) mediated glutathione (GSH) depletion on hepatic and renal cortical blood flow (perfusion), plasma GSH, and portal prostacyclin (6-ketoPGF1 alpha) and thromboxane (TxB2) were determined in anaesthetized swine. 2. Although DEM depleted hepatic GSH to 25% of control, plasma GSH increased 10-fold in comparison to controls. DEM caused a drop in blood pressure and renal cortical perfusion but had no effect on hepatic perfusion or portal 6-ketoPGF1 alpha or TxB2 levels. 3. Possibly, the unexpected rise in plasma GSH may have inhibited prostanoid synthesis, preventing any alterations in tissue perfusion that may have occurred following tissue GSH depletion.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Female; Glutathione; Kidney Cortex; Liver; Male; Maleates; Perfusion; Portal Vein; Swine; Thromboxane B2

1. The effect of glutathione (GSH) depletion on rabbit renal medullary homogenate 6-ketoPGF1 alpha and TxB2 synthesizing capability was investigated. 2. GSH depletion in vivo with diethyl maleate (DEM) produced higher (P less than 0.05) 6-ketoPGF1 alpha and TxB2 renal medullary levels compared to controls. Homogenization and incubation lowered (P less than 0.05) GSH such that there were no differences in GSH between treatments after 5 min of incubation. By 30 min, GSH was lower (P less than 0.05) and 6-ketoPGF1 alpha higher (P less than 0.05) in homogenates from controls in comparison to those from DEM-treated rabbits. 3. The results indicate GSH depletion increased 6-ketoPGF1 alpha levels in rabbit renal medulla in vivo but subsequent GSH catabolism prevented assessing the effect of this GSH depletion on prostanoid synthesizing capability.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Glutathione; In Vitro Techniques; Kidney Medulla; Male; Maleates; Oxidation-Reduction; Rabbits; Radioimmunoassay; Thromboxane B2

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.

Topics: Animals; Buthionine Sulfoximine; Epoprostenol; Glutathione; Kidney; Liver; Lung; Male; Maleates; Methionine Sulfoximine; Methylcholanthrene; Rats; Rats, Inbred Strains; Thromboxane B2

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.

Topics: 6-Ketoprostaglandin F1 alpha; Acid-Base Equilibrium; Animals; Blood Pressure; Glutathione; Heart Rate; Indomethacin; Liver; Liver Circulation; Male; Maleates; Rabbits; Thromboxane B2