Inhibition of glutathione excretion, bile flow, and alterations of the glutathione status by 4-nitrosophenetol during perfusion of rat livers.

(1) Hemoglobin-free single-pass perfusion of isolated rat livers was carried out with various concentrations of 4-nitrosophenetol (NOPt). (2) NOPt, up to 2 mumol/min/g liver wet wt., was reduced by the liver with formation of N-hydroxy-4-phenetidine (NHOHPt), 4-phenetidine (NH2Pt), phenacetin and polar metabolites. (3) Three per cent of NOPt was irreversibly bound to liver proteins after a load of 20 mumol/g liver wet wt. After 30 min perfusion, 0.2 mumol of liver glutathione was lost by 1 mumol NOPt infused. (4) Bile flow and glutathione release by the bile decreased rapidly during NOPt perfusion. (5) Glutathione release of the livers into venous effluent was diminished by NOPt and was stimulated only slightly by t-butylhydroperoxide (BOOH). Because BOOH reduction and glutathione peroxidase were not altered and intracellular glutathione disulfide (GSSG) levels were elevated, inhibition of the GSSG excretory mechanism is assumed.