Noguchi M, Nitoh S, Mabuchi M, Kawai Y
Safety Research Laboratory, Tanabe Seiyaku Co., Ltd., Osaka, Japan.
Exp Anim. 1996 Apr;45(2):161-70. doi: 10.1538/expanim.45.161.
In experiment 1, the amount of aniline (AN) metabolites in the primary cell culture medium of the liver cells obtained from ethionine (ET)-treated rats was compared with that of the control (normal) rats. Although the metabolites detected in both groups were p-aminophenol (p-AP), N-acetyl-p-AP (AAP), acetoanilide (AAN), AAP-glucuronide (AAPG), phenylhydroxylamine sulfate (PHAS) and p-AP-glucuronide (p-APG), the amount of AAP was lower and that of p-APG was markedly higher in the ET-treated rats than in the control rats. In experiment 2, phenobarbital (PB) was orally administered to the ET-treated and control rats at a dose of 100 mg/kg. The time course changes in AN metabolites in the primary cell culture medium of liver cells obtained at 2 or 48 hr after PB treatment were compared with those without PB treatment. In the ET-treated rats, the amount of PHAS was slightly higher at 2 hr after PB treatment, and that of AAP was lower and that of p-APG was higher at 48 hr after PB treatment as compared with those without PB treatment. In the control rats, the amounts of AAP, AAN, p-AP and p-APG at 2 hr after PB treatment remained lower than those without PB treatment, and that of AAP was markedly lower and that of p-APG was higher at 48 hr after PB treatment as compared with those without PB treatment. These findings indicated greater detoxication in the primary liver cell culture in the ET-treated rats than in the control rats. Furthermore, detoxication was greater in the primary cell culture of liver cell obtained from the ET-treated rats after PB treatment than from those without PB treatment, because the production of acetylates (AAP) decreased and p-APG increased (induction of conjugated enzyme) in the PB treatment group.
在实验1中，将从乙硫氨酸（ET）处理的大鼠获得的肝细胞原代细胞培养基中苯胺（AN）代谢物的量与对照（正常）大鼠的进行比较。尽管在两组中检测到的代谢物均为对氨基苯酚（p - AP）、N - 乙酰 - p - AP（AAP）、乙酰苯胺（AAN）、AAP - 葡萄糖醛酸苷（AAPG）、苯羟胺硫酸盐（PHAS）和p - AP - 葡萄糖醛酸苷（p - APG），但ET处理的大鼠中AAP的量较低，而p - APG的量明显高于对照大鼠。在实验2中，以100 mg/kg的剂量给ET处理的大鼠和对照大鼠口服苯巴比妥（PB）。将PB处理后2小时或48小时获得的肝细胞原代细胞培养基中AN代谢物的时间进程变化与未进行PB处理的情况进行比较。在ET处理的大鼠中，与未进行PB处理相比，PB处理后2小时PHAS的量略高，PB处理后48小时AAP的量较低而p - APG的量较高。在对照大鼠中，PB处理后2小时AAP、AAN、p - AP和p - APG的量仍低于未进行PB处理的情况，且与未进行PB处理相比，PB处理后48小时AAP的量明显较低而p - APG的量较高。这些发现表明，ET处理的大鼠的原代肝细胞培养中的解毒作用比对照大鼠更强。此外，PB处理后，从ET处理的大鼠获得的肝细胞原代细胞培养中的解毒作用比未进行PB处理的更强，因为PB处理组中乙酰化物（AAP）的产生减少而p - APG增加（共轭酶的诱导）。
