Inhibition of creatine kinase activity in rat brain by methyl bromide gas.
Inhibition of creatine kinase activity in rat brain by methyl bromide gas.
复制标题
溴甲烷气体抑制大鼠脑中肌酸激酶活性。
DOI：
10.1080/08958370126865
复制
发表时间：
2001
影响因子：
2.1
通讯作者：
H. Igisu
中科院分区：
文献类型：
--
作者：
T. Hyakudo;H. Hori;I. Tanaka;H. Igisu
大鼠暴露于290或495 ppm溴甲烷气体中，每天6小时，每周3次，持续4 ~ 8周。肌酸激酶（CK），天冬氨酸氨基转移酶（ASAT），乳酸脱氢酶（LDH）的活动和溴离子浓度进行了测量，在8个区域的大脑。溴甲烷气体抑制CK活动在大脑的所有区域，虽然抑制往往是最小的小脑（半球和蚓部）和最大的脑干（下丘脑，中脑和延髓）。溴甲烷抑制CK活性的剂量低于对中枢神经系统的组织学损害。除纹状体中的ASAT或LDH活性受到轻微抑制外，未观察到ASAT或LDH活性受到抑制。随着剂量的增加（290至495 ppm）或暴露时间的延长（4至8周），CK活性的抑制并未明显增加。虽然50%的恢复CK活动和溴离子的半衰期同意以及在延髓，CK活动和溴离子浓度的变化并不相关，否则。因此，脑内CK活性的抑制似乎是溴甲烷中毒的敏感指标，并可能与溴甲烷神经毒性的发生有关。这种抑制作用可能是由溴甲烷本身引起的，而不是由溴离子引起的。当在体外用溴甲烷气体鼓泡检查对脑匀浆中酶活性的影响时，在暴露的15秒内观察到CK抑制。二硫苏糖醇抑制CK抑制，而N-乙酰半胱氨酸没有。这些观察结果表明，甲基溴可能攻击CK分子中的位点不同于环氧乙烷或丙烯酰胺攻击的位点。
Rats were exposed to 290 or 495 ppm methyl bromide gas for 6 h/day, 3 times/wk for 4 to 8 wk. Creatine kinase (CK), aspartate aminotransferase (ASAT), and lactate dehydrogenase (LDH) activities and bromide ion concentrations were measured in eight regions of the brain. Methyl bromide gas inhibited CK activities in all regions of the brain, though the inhibition tended to be smallest in the cerebellum (hemisphere and vermis) and largest in the brainstem (hypothalamus, midbrain, and medulla oblongata). The dose of methyl bromide to inhibit CK activities was lower than that to damage the central nervous system histologically. No inhibition of ASAT or LDH activities was seen except for a slight inhibition of these in striatum. Inhibition of CK activities did not increase clearly on increasing dose (290 to 495 ppm) or on prolonging exposure period (4 to 8 wk). Although 50% recovery of CK activities and the half-life of bromide ion agreed well in the medulla oblongata, changes in CK activities and bromide ion concentrations did not correlate otherwise. Thus, inhibition of CK activities in brain appears to be a sensitive indicator of methyl bromide intoxication, and may be related to genesis of its neurotoxicity. The inhibition seems to be caused by methyl bromide itself rather than by bromide ion. When effects on enzyme activities in brain homogenate were examined in vitro by bubbling with methyl bromide gas, CK inhibition was seen within 15 s of exposure. Dithiothreitol suppressed the CK inhibition, whereas N-acetylcysteine did not. These observations suggest that methyl bromide may attack sites in the CK molecule different from those attacked by ethylene oxide or acrylamide.