카드뮴에 의한 흰쥐 뇌조직의 Biogenic amine 변동과 glutathione의 영향

Abstract

카드윰(10 ㎍)을 뇌실내에 투여하여 뇌조직내에 biogenic amine 과 그 대사산물 함량에 미치는 영향을 알아보았으며 아울러 조직내 glutathione(GSH)과의 관련성을 추구하였다. 카드뮴 투여 후 처음 24시간에는 신경전달물질의 함량 변동이 거의 나타나지 않았으나, 48시간에서는 크게 증가하였고 이러한 현상은 뇌조직의 모든 부위에서 나타났다. Y-Glutamylcysteine synthetase 의 선택적 억제제인 L-buthionine-(S,R)-sulfoximine(BSO; 3.2 mg) 전처치로 뇌내 GSH의 양은 정상보다 60 % 정도 감소되었으나 BSO의 투여만으로는 뇌조직내 biogenic amine 및 대사산물의 함량에 변동이 없었다 BS0 전처치 후 24시간 이상 경과시킨 후 카드뮴을 투여한 경우 뇌조직내 biogenic amino및 대사산물의 함량은 처음 6시간에 크게 증가한 다음 12시간 및 24시간에서 약간 감소하였다가 48시간에 다시 크게 증가하였다. 이러한 결과로 보아 GSH은 카드뮴에 의한 뇌내 biogenic amine 및 그 대사산물의 함량 변동을 억제하며, 특히 GSH은 카드뮴 신경독성의 초기방어에 중요한 역할을 하는 것으로 생각된다.;Acute effects of cadmium on the central monoamines and their metabolites were studied in relation to the role of glutathione. The biogenic amines were measured in various brain regions at 6, 12, 24 and 48 hours after intracerebroventricular(i.c.v.) injection of CdCl_(2)(10 ㎍). The levels of monoamine neurotransmitters and their metabolites increased time-dependently. These effects were prominent at 48 hour after i.c.v. cadmium, while only minimal changes were observed during the first 12 hours. This phenomenon occurred almost invariably in all the brain regions and in measured monoamines with their metabolites. L-Buthionine-[S,R]-sulfoximine(BSO; 3.2 mg), 3 Selective inhibitor of Υ-glutamylcysteine synthetase was administered 24 hours before cadmium, which depleted brain glutathione about 60% of the control level. BSO itself did not change the levels of monoamines and their metabolites. When BSO was pretreated before cadmium, the pattern of amino change was three phasic. Increased levels of the monoamines and their metabolites occurred up to the first 6 hours after cadmium, while cadmium itself caused minimal changes. At 24 hours after cadmium, those levels were variable. However, increased levels of those reappeared at 48 hours after cadmium. It is noteworthy that increased levels of monoamines and their metabolites at 48 hours after cadmium i.c.v were not changed by BSO pretreatment. These results suggest that expression of cadmium toxicity may have different phases, and that glutathione exerts its protective effects in the early phase of cadmium toxicity.