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蓖麻毒素口服毒性的生化研究。IV. 大鼠口服蓖麻毒素的归宿

Biochemical studies on oral toxicity of ricin. IV. A fate of orally administered ricin in rats.

作者信息

Ishiguro M, Tanabe S, Matori Y, Sakakibara R

机构信息

Department of Biochemistry, School of Clinical Pharmaceutical Sciences, Nagasaki University, Japan.

出版信息

J Pharmacobiodyn. 1992 Apr;15(4):147-56. doi: 10.1248/bpb1978.15.147.

DOI:10.1248/bpb1978.15.147
PMID:1494977
Abstract

After oral administration of ricin in rats, its distribution in the gastrointestinal tract, body fluids and principal organs was determined by an enzyme immunoassay, and the immunoreactive ricin detected was identified by gel filtration followed by sodium dodecyl sulfate polyacrylamide gel electrophoresis, protein blotting and the immunobinding method. When ricin D (10 mg/kg rat) was given orally to a rat, which dose is equivalent to 1/3 LD50, about 75% of the ricin was found in the stomach and small intestine within 2 h, and most of it was transferred to the large intestine after 24 h. It was also demonstrated by an in vitro toxicity test of immunoreactive ricin in the blood and lymph obtained from the intoxicated rats that a part of the ricin was absorbed from the small intestine into the tissues and organs via the circulatory systems (lymphatic and blood vessels) as the active ricin. The participation of the blood vessels was greater in the absorption of ricin from the gastrointestinal tract than that of the lymphatic system. Ricin, after absorption, was detected in liver and spleen and ricin found in the liver was predominantly in the form of intact ricin, although an undetectable amount of ricin in other organs cannot be eliminated. These results infer that a small fraction of orally-given ricin was transferred to the circulating system and was responsible for rat's death as in the case of i.p. administration.

摘要

给大鼠口服蓖麻毒素后,通过酶免疫测定法确定其在胃肠道、体液和主要器官中的分布,并通过凝胶过滤,随后进行十二烷基硫酸钠聚丙烯酰胺凝胶电泳、蛋白质印迹和免疫结合法,对检测到的免疫反应性蓖麻毒素进行鉴定。当给大鼠口服蓖麻毒素D(10mg/kg大鼠)时,该剂量相当于1/3 LD50,在2小时内约75%的蓖麻毒素存在于胃和小肠中,24小时后大部分转移至大肠。对中毒大鼠血液和淋巴中免疫反应性蓖麻毒素的体外毒性试验也表明,一部分蓖麻毒素以活性蓖麻毒素的形式通过循环系统(淋巴管和血管)从小肠吸收进入组织和器官。蓖麻毒素从胃肠道吸收过程中,血管的参与程度比淋巴系统更大。吸收后,在肝脏和脾脏中检测到蓖麻毒素,肝脏中发现的蓖麻毒素主要为完整蓖麻毒素的形式,尽管其他器官中未检测到的蓖麻毒素量也不能排除。这些结果表明,口服的一小部分蓖麻毒素转移至循环系统,并如腹腔注射给药的情况一样导致大鼠死亡。

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