异烟肼处理的大鼠中还原型谷胱甘肽及相关氨基酸的抗惊厥作用

Anti-convulsant effects by reduced glutathione and related aminoacids in rats treated with isoniazid.

作者信息

Pinelli A, Trivulzio S, Colombo-Zefinetti G, Tofanetti O

机构信息

Department of Pharmacology, University of Milan, Italy.

出版信息

Toxicology. 1988 Jan;48(1):103-7. doi: 10.1016/0300-483x(88)90064-9.

DOI:10.1016/0300-483x(88)90064-9

PMID:2892286

Abstract

Rats were treated with different doses of isoniazid (INH) causing convulsions. Lethal dose (DL50) and effective convulsant dose (ED50) were calculated. Reduced glutathione (GSH) and related aminoacids were administered to rats receiving INH: the latency and duration of convulsions were recorded; cerebral gamma-aminobutyric acid (GABA) concentrations were determined in rats receiving INH and an association of GSH and INH. GSH and its related aminoacids as cysteine and glycine greatly decreased the duration of INH-induced seizures, while glutamic acid did not protect against convulsions caused by INH. Furthermore, INH causes a decrease in cerebral GABA levels to about half and GSH repeated pretreatment did, however, not prevent the INH induced decline of GABA content: hence, the anticonvulsant effect of GSH can not be ascribed to the restoration of normal levels of anti-epilectically acting GABA, but can be attributed to cysteine and glycine, aminoacids linked to GSH.

摘要

用不同剂量的异烟肼（INH）处理大鼠，使其发生惊厥。计算致死剂量（DL50）和有效惊厥剂量（ED50）。将还原型谷胱甘肽（GSH）及相关氨基酸给予接受INH的大鼠：记录惊厥的潜伏期和持续时间；测定接受INH以及接受GSH与INH联合处理的大鼠大脑中的γ-氨基丁酸（GABA）浓度。GSH及其相关氨基酸半胱氨酸和甘氨酸可显著缩短INH诱导的惊厥持续时间，而谷氨酸不能预防INH引起的惊厥。此外，INH使大脑GABA水平降低约一半，然而，GSH重复预处理并不能防止INH诱导的GABA含量下降：因此，GSH的抗惊厥作用不能归因于恢复具有抗癫痫作用的GABA的正常水平，而可归因于与GSH相关的氨基酸半胱氨酸和甘氨酸。