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-ketoPGF1-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-ketoPGF1-alpha and TxB2 or circulating levels of 6-ketoPGF1-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-ketoPGF1-alpha in non-induced rats. In contrast, depletions of hepatic, renal and pulmonary tissue GSH by DEM (I mL/kg body wt) to 12, 50 and 30% of control, respectively, were associated with elevations of 6-ketoPGF1-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-ketoPGF1-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-ketoPGF1-alpha levels in vivo.