Elovaara E, Kivistö H, Vainio H
Arch Toxicol. 1983 Feb;52(2):109-21. doi: 10.1007/BF00354771.
Male Wistar rats received methyl methacrylate monomer (MMA) i.p. in olive oil 1.0 g/kg body weight on 3 successive days. The weight of the livers and kidneys, and the body weights did not differ from their controls. On the fifth day after treatment, hepatic NADPH-cytochrome c reductase, 7-ethoxycoumarin 0-deethylase and the 2,5-diphenyloxazole hydroxylase exhibited maximal decreases in activity (25%, 58%, 36%, respectively) without any coincident effect on the total amount of cytochrome P-450 hemoprotein itself. One week later these activities had returned to control levels. The enzymatic changes in the kidneys were smaller in magnitude, and they were also reversed sooner. A single i.p. dose of MMA (2 g/kg body weight) caused elevation of serum alanine aminotransferase activity. A tenfold increase of the excretion rate of urinary thioethers was also discovered. The hepatic reduced glutathione (GSH) was depleted in 3 h to 20% and the GSSG to half of the value in controls. In kidneys, the GSH was decreased to 48% in 3 h before an apparent phase of overrecovery. At the end of the 24 h observation period, cytochrome P-450 concentrations were somewhat decreased in the liver. The GSH contents showed dose and time-dependent reversible decreases in isolated hepatocytes when incubated for 2 h in a medium containing MMA at the nominal concentrations of 0, 2, 5, or 10 mM. None of the treatments affected either the content of cytochrome P-450 or the viability of the liver cells.
雄性Wistar大鼠连续3天腹腔注射溶于橄榄油中的甲基丙烯酸甲酯单体（MMA），剂量为1.0 g/kg体重。肝脏和肾脏的重量以及体重与对照组相比无差异。治疗后第5天，肝脏NADPH - 细胞色素c还原酶、7 - 乙氧基香豆素O - 脱乙基酶和2,5 - 二苯基恶唑羟化酶的活性出现最大程度下降（分别为25%、58%、36%），而细胞色素P - 450血红蛋白本身的总量未受任何影响。1周后这些活性恢复到对照水平。肾脏中的酶变化幅度较小，恢复也更快。单次腹腔注射MMA（2 g/kg体重）导致血清丙氨酸转氨酶活性升高。还发现尿硫醚排泄率增加了10倍。肝脏中的还原型谷胱甘肽（GSH）在3小时内降至对照值的20%，氧化型谷胱甘肽（GSSG）降至对照值的一半。在肾脏中，GSH在3小时内降至48%，之后出现明显的过度恢复阶段。在24小时观察期结束时，肝脏中的细胞色素P - 450浓度有所下降。当在含有0、2、5或10 mM标称浓度MMA的培养基中孵育2小时时，分离的肝细胞中GSH含量呈剂量和时间依赖性可逆下降。所有处理均未影响细胞色素P - 450的含量或肝细胞的活力。
