MOLECULAR MECHANISM OF INFLAMMATORY AND IMMUNOLOGICAL FACTORS INVOLVED IN DRUG-INDUCED LIVER INJURY
Project/Area Number |
09672209
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Biological pharmacy
|
Research Institution | Showa Pharmaceutical University |
Principal Investigator |
HOJO Hiroshi FACULTY OF PHARMACEUTICAL SCIENCES, DEPT. OF HYGIENIC CHEMISTRY, SHOWA PHARMACEUTICAL UNIVERSITY, 薬学部, 教授 (90004621)
|
Project Period (FY) |
1997 – 1999
|
Project Status |
Completed (Fiscal Year 1999)
|
Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1999: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1998: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1997: ¥1,600,000 (Direct Cost: ¥1,600,000)
|
Keywords | Liver injury / carbon tetracloride / interleukin-6 / cytokine / rat / dexamethasone / インターロイキン6 / デキサメサゾン / エンドトキシン |
Research Abstract |
We have investigated the role of inflammatory and immune mediators in the carbon tetrachloride induced liver injury models. An administration of carbon tetrachloride through the subcutaneous (s.c.) or intraperitoneal (I.p.) route induced interleukln-6 (IL-6) in plasma with a peak at 8 and 4 hr later, respectively, but that through the per os (p.s.) route did not. The maker hepatic enzyme activities were increased with a peak 24 hr to 48 hr after carbon tetrachloride administration, however, the rate of increase was higher through the p.o. route than through the s.c. or I.p. route. As ratios of the vehicle (corn oil) to carbon tetrachloride were increased, the IL-6 induction was decreased and the leak of hepatic enzymes was augmented. Pretreatment with dexamethasone markedly suppressed the IL-6 induction and enhanced the enzyme leaks in the rats treated with carbon tetrachloride through the s.c. or I.p. route. These results represent the close reverse correlation between IL-6 induction and liver injury, suggesting the IL-6 induced in the early phase after carbon tetrachloride might play a suppressive role in the development of the liver injury.
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Report
(4 results)
Research Products
(3 results)