Relationship between GST Yp Induction and Hepatocyte Proliferation in Rats Treated with Phase II Drug Metabolizing Enzyme Inducers
Relationship between GST Yp Induction and Hepatocyte Proliferation in Rats Treated with Phase II Drug Metabolizing Enzyme Inducers
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DOI：
10.1177/0192623308315359
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发表时间：
2008-04-01
影响因子：
1.5
通讯作者：
Nakayama, Hiroyuki
中科院分区：
文献类型：
--
作者：
Makino, Toshihiko;Ishikawa, Kayoko;Nakayama, Hiroyuki
丁基羟基茴香醚（BHA）和1，2-双（2-吡啶基）乙烯（2 PY-e）是II相药物代谢酶诱导剂，其引起肝肿大而不引起肝细胞肥大，并诱导谷胱甘肽S-转移酶Yp（GST Yp，pi类GST），其被称为肿瘤标志物。为了评价GST Yp诱导和肝细胞增殖之间的关系，雄性F344/DuCrj大鼠用BHA、2 PY-e或苯巴比妥（PB）处理3天或7天。所有三种化学物质在三天和七天后都会导致肝脏重量增加。免疫组织化学检查显示，BHA和2 PY-e诱导GST Yp在肝细胞的门脉周围和小叶中心区在第三和第七天，分别，而PB没有。BrdU标记指数显着增加，发现在每个三天的治疗组的大鼠肝脏，但标记指数的BHA治疗的大鼠肝脏下降到对照水平，在第七天，虽然高标记指数的2 PY-e和PB持续到第七天。双重免疫染色证实，在BHA和2 PY-e处理的大鼠中，BrdU阳性细胞核对应于GST Yp阳性肝细胞。提示BHA或2 PY-e诱导的GST Yp表达与肝细胞增殖有一定关系。
Butylated hydroxyanisole (BHA) and 1,2-bis(2-pyridyl)ethylene (2PY-e) are phase II drug metabolizing enzyme inducers which cause hepatomegaly without hepatocyte hypertrophy and induce glutathione S-transferase Yp (GST Yp, pi-class GST), which is known as a tumor marker. To evaluate the relationship between GST Yp induction and hepatocyte proliferation, male F344/DuCrj rats were treated with BHA, 2PY-e, or phenobarbital (PB) for three or seven days. All three chemicals caused increases in liver weight after three and seven days. Immunohistochemical examinations revealed that BHA and 2PY-e induced GST Yp in the hepatocytes of the periportal and centrilobular areas at three and seven days, respectively, whereas PB did not. Significant increases in the BrdU labeling indices were found in the livers of rats in each of the three-day treatment groups, but the labeling index of rat livers treated with BHA was decreased to the control level at seven days, although the high labeling indices of 2PY-e and PB persisted at seven days. Double immunostaining confirmed that BrdU-positive nuclei corresponded to GST Yp-positive hepatocytes in both BHA and 2PY-e treated rats. These results suggest that the GST Yp induction caused by BHA or 2PY-e has some kind of relationship with hepatocyte proliferation.