Schnell R C, Pence D H
Toxicol Lett. 1981 Sep;9(1):19-25. doi: 10.1016/0378-4274(81)90169-7.
Cadmium (Cd) produced a marked sex-related difference with respect to inhibition of the hepatic microsomal monooxygenase enzyme system in the rat. Following in vivo cadmium (2 mg/kg i.p.) treatment, significant decreases in the levels of cytochrome P-450, significant reductions in the magnitudes of spectral binding (aniline or ethylmorphine), and significant inhibitions of microsomal metabolism (aniline and ethylmorphine) were observed with microsomes isolated from male but not female rats. Of these parameters only aniline metabolism was significantly altered in females. Following the in vitro addition of Cd (10(-6) M to 10(-3) M) to hepatic microsomes isolated from untreated male or female rats, sex-related changes were also observed in these parameters. Significant, concentration-dependent reductions were observed in cytochrome P-450 levels of both sexes but the males showed greater sensitivity to the cadmium effect. With respect to binding spectra, cadmium addition produced a concentration dependent inhibition of aniline only in the male rat. Ethylmorphine binding was inhibited only at the higher cadmium concentrations in both sexes. With respect to drug metabolism, cadmium addition inhibited both aniline and ethylmorphine metabolism in male rats and only aniline metabolism in female rats. These results showed that there are sex-related differences in the interaction of the hepatic microsomal monooxygenase enzyme system with cadmium both after in vitro addition as well as in vivo treatment with the metal.
镉（Cd）在抑制大鼠肝脏微粒体单加氧酶系统方面表现出明显的性别差异。经腹腔注射给予体内镉（2毫克/千克）处理后，从雄性大鼠而非雌性大鼠分离出的微粒体中，观察到细胞色素P - 450水平显著降低、光谱结合量（苯胺或乙基吗啡）显著减少以及微粒体代谢（苯胺和乙基吗啡）显著受抑制。在这些参数中，只有雌性大鼠的苯胺代谢有显著改变。在从未处理的雄性或雌性大鼠分离出的肝脏微粒体中体外添加镉（10⁻⁶摩尔/升至10⁻³摩尔/升）后，在这些参数中也观察到了性别相关变化。两性的细胞色素P - 450水平均出现显著的浓度依赖性降低，但雄性对镉的影响表现出更高的敏感性。关于结合光谱，添加镉仅在雄性大鼠中产生浓度依赖性的苯胺抑制。乙基吗啡结合仅在两性的较高镉浓度下受到抑制。关于药物代谢，添加镉抑制了雄性大鼠的苯胺和乙基吗啡代谢，而仅抑制了雌性大鼠的苯胺代谢。这些结果表明，无论是体外添加还是用该金属进行体内处理后，肝脏微粒体单加氧酶系统与镉的相互作用均存在性别相关差异。
