Sultatos L G, Minor L D
Toxicology. 1985 Aug;36(2-3):159-69. doi: 10.1016/0300-483x(85)90051-4.
Single-pass perfusion in situ of mouse livers with the organophosphate paraoxon resulted in formation of p-nitrophenol (PNP), p-nitrophenyl sulfate (PNPS), and p-nitrophenyl-beta-D-glucuronide (PNPG). Following initiation of perfusion of paraoxon steady--state conditions were achieved in 15-25 min, at which time the extraction ratio was 0.55 (S.D. = 0.05). This suggests the capacity of mouse liver to biotransform paraoxon is not as great as previously reported. At all concentrations of paraoxon examined the amount of PNPS produced exceeded that of PNPG. However, as the concentration of paraoxon increased the relative proportion of PNP to PNPS and PNPG increased, indicating the capacity of liver to biotransform paraoxon exceeded the capacity to biotransform PNP. Single-pass perfusion in situ of mouse livers with PNP resulted in production of PNPS and PNPG. As with paraoxon, steady-state conditions were achieved in 15-25 min. The extraction ratio of PNP, as well as the metabolic profile, changed markedly with varying concentrations of PNP. At PNP reservoir concentrations of 4 microM or less the extraction ratio of PNP was 1, with all PNP metabolized to PNPS. As PNP concentrations increased (up to 75 microM) both unchanged PNP and PNPG appeared in the effluent. Thus the hepatic biotransformation of PNP was clearly dependent on substrate concentration.
用有机磷酸酯对氧磷对小鼠肝脏进行原位单次灌注，导致对硝基苯酚（PNP）、对硝基苯硫酸酯（PNPS）和对硝基苯基-β-D-葡萄糖醛酸苷（PNPG）的形成。对氧磷灌注开始后，15 - 25分钟内达到稳态，此时提取率为0.55（标准差 = 0.05）。这表明小鼠肝脏生物转化对氧磷的能力不如先前报道的那么强。在所检测的所有对氧磷浓度下，产生的PNPS量超过了PNPG量。然而，随着对氧磷浓度的增加，PNP与PNPS和PNPG的相对比例增加，表明肝脏生物转化对氧磷的能力超过了生物转化PNP的能力。用PNP对小鼠肝脏进行原位单次灌注导致PNPS和PNPG的产生。与对氧磷一样，15 - 25分钟内达到稳态。PNP的提取率以及代谢谱随PNP浓度的变化而显著变化。在PNP储库浓度为4 microM或更低时，PNP的提取率为1，所有PNP都代谢为PNPS。随着PNP浓度增加（高达75 microM），流出物中出现了未变化的PNP和PNPG。因此，PNP的肝脏生物转化显然取决于底物浓度。
