A STUDY OF THE EFFECTS OF VIGABATRIN ON THE CENTRAL-NERVOUS-SYSTEM AND RETINA OF SPRAGUE DAWLEY AND LISTER-HOODED RATS
A STUDY OF THE EFFECTS OF VIGABATRIN ON THE CENTRAL-NERVOUS-SYSTEM AND RETINA OF SPRAGUE DAWLEY AND LISTER-HOODED RATS
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DOI：
10.1177/019262338701500203
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发表时间：
1987-01-01
影响因子：
1.5
通讯作者：
NEWBERNE, JW
中科院分区：
文献类型：
--
作者：
BUTLER, WH;FORD, GP;NEWBERNE, JW
氨己烯酸 (γ-乙烯基 GABA) 是一种酶激活的、不可逆的 GABA 转氨酶抑制剂，对白化 Sprague Dawley 大鼠和有色 Lister-Hooded 大鼠口服给药。在 Sprague Dawley 大鼠中观察到剂量依赖性视网膜病变，其组织学特征为外核层破坏，但在 Lister-Hooded 大鼠中未观察到，表明这种改变与色素的缺失有关。这种病变与光和某些药物在白化大鼠中引起的病变相似。此外，在两种大鼠品系中均观察到大脑髓磷脂空泡形成，这与氨己烯酸其他毒性研究的结果一致。在所有情况下，空泡形成仅限于有髓鞘，是由于髓鞘在周期内线处分离所致。没有证据表明受影响区域有脱髓鞘、轴突变性或邻近结构损伤。空泡形成在组织学上与某些其他化合物（例如异烟肼、六氯酚和三乙基锡）在大鼠中诱导的空泡形成相似，但不同之处在于它是局灶性分布，仅限于大脑，并且在停止治疗后是可逆的。
Vigabatrin (.gamma.-vinyl GABA), an enzyme-activated, irreversible inhibitor of GABA transaminase, was administered orally to albino Sprague Dawley and pigmented Lister-Hooded rats. A dose-dependent retinal lesion characterized histologically by disruption of the outer nuclear layer was observed in the Sprague Dawley rat but not in Lister-Hooded rats, indicating that this alteration is related to the absence of pigment. The lesion is similar to that induced in albino rats by light and certain drugs. In addition, myelin vacuolation of the brain was observed in both rat strains,consistent with the findings of other toxicity studies with vigabatrin. In all cases, the vacuolation was limited to myelinated tracts and resulted from separation of the myelin sheath at the intraperiod line. There was no evidence of demyelination, axonal degeneration or damage to contiguous structures in the affected reas. The vacuolation is histologically similar to that induced in rats by certain other compounds such as isoniazid, hexachlorophene, and triethyltin, but differs in that it is focal in distribution, it is limited to the brain, and is reversible upon cessation of treatment.