1990 Fiscal Year Final Research Report Summary
Preparation of Polymer Conjugated Bilirubin Oxidase and Development of Therapeatic Method for Jaundice.
| Project/Area Number |
63870032
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Research Field |
Gastroenterology
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| Research Institution | Kumamoto University |
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Principal Investigator |
MAEDA Hiroshi Kumamoto Univ. Med. School. Dept. Microbiol., Professor, 医学部, 教授 (90004613)
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| Co-Investigator(Kenkyū-buntansha) |
KOJIMA Yuichiro Kumamoto Univ. Med. School, Dept. Microbiol., Assist., 医学部, 助手 (50215258)
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| Project Period (FY) |
1988 – 1990
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| Keywords | Bilirubin / Jaundice / Kernicterus / Bilirubin oxidase / Polyethylene glycol conjugate / Fluminant hepatitis / Hepatitis / Liver function |
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| Research Abstract |
The clinical cause of jaundice is known to be due to elevated plasma level of bilirubin, and its removal is a critical factor. We have elucidated that bilirubin is toxic to even cells in culture in that it suppress DNA, RNA and protein syntheses and membrane transport. A microbial enzyme called bilirubin oxidase can detoxify all these toxic effects. The degradation products of bilirubin by this enzyme were found to be excreted from the kidney, thus, transhepatic elimination is not required for detoxification. Polymer conjugated bilirubin oxidase does the same job as expected in vitro. When rats were artificially made jaundice by ligating and cutting the bile duct and then, they were treated with polymer-conjugated bilirubin oxidase by intravenous (i. v.) injection. The result was that the polymer conjugate exhibited a pronounced reduction in the plasma bilirubin level to the normal upto 48hr after injection, whereas the native oxidase did so only a little at 30 min post injection only. Furthermore immunological problems associated with injection with native bilirubin oxidase was removed more than 95% in the polymer conjugated one. There was little toxicity observed upon i. v. injection of this polymer-enzyme conjugate at the therapeutic dose. Thus, its clinical application appears feasible.
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