Calder I C, Yong A C, Woods R A, Crowe C A, Ham K N, Tange J D
Chem Biol Interact. 1979 Oct;27(2-3):245-54. doi: 10.1016/0009-2797(79)90129-7.
Inducers and inhibitors of the microsomal mixed function oxidase system have no consistent effect upon the nephrotoxicity of p-aminophenol, or on binding of the compound in vivo to cell protein. p-[ring-3H]Aminophenol was bound in vitro to kidney microsomal protein and to a lesser extent to liver. The binding was enhanced by preincubation of the p-aminophenol in air and inhibited by ascorbate, GSH, N2 and NADPH. These findings indicate that in contrast to paracetamol hepatoxicity which is dependent upon the mixed function oxidase system, that nephrotoxicity of p-aminophenol is dependent upon oxidation to a toxic metabolite by some other pathway. A similar metabolite may be responsible for the nephrotoxic action of phenacetin.
微粒体混合功能氧化酶系统的诱导剂和抑制剂对对氨基酚的肾毒性或该化合物在体内与细胞蛋白的结合没有一致的影响。对-[环-3H]氨基酚在体外与肾脏微粒体蛋白结合，与肝脏的结合程度较低。对氨基酚在空气中预孵育可增强这种结合，而抗坏血酸、谷胱甘肽、氮气和烟酰胺腺嘌呤二核苷酸磷酸（NADPH）可抑制这种结合。这些发现表明，与依赖于混合功能氧化酶系统的对乙酰氨基酚肝毒性相反，对氨基酚的肾毒性依赖于通过其他途径氧化为有毒代谢物。一种类似的代谢物可能是对乙酰氨基酚肾毒性作用的原因。
