Project/Area Number |
05670358
|
Research Category |
Grant-in-Aid for General Scientific Research (C)
|
Allocation Type | Single-year Grants |
Research Field |
Public health/Health science
|
Research Institution | Sapporo Medical University |
Principal Investigator |
SUGAWARA Naoki Sapporo Medical University, Department of Public Health, Associate Professor, 医学部, 助教授 (60045523)
|
Co-Investigator(Kenkyū-buntansha) |
SUGAWARA Chieko Sapporo Medical University, Department of Public Health, Instructor, 医学部, 助手 (50045431)
|
Project Period (FY) |
1993 – 1994
|
Project Status |
Completed (Fiscal Year 1994)
|
Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1994: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1993: ¥1,000,000 (Direct Cost: ¥1,000,000)
|
Keywords | Copper metabolism / Metallothionein / LEC rat / Hepatitis / Liver cancer / Free radicals |
Research Abstract |
1.Mechanism of Cu accumulation in the liver. It seems likely that a gross deposit of hepatic Cu is due to a lack of biliary excretion of Cu. The lack is partly dependent on the dysfunction of lysosmes. The increased-Cu induces metallothionein (MT) synthesis, resulting in sequestration of Cu in the MT.Finally, the vicious cycle of Cu stimulates the Cu deposition in the LEC rat liver. 2.Biliary excretion of Cu and metallothionein (MT). When Cd was qiven LEC rats at a low level, there was no difference of hepatic Cd concentration between LEC and Fischer rats. Accordingly, the abnormal metabolism found in LEC rats is specific for Cu. Biliary excretion of Cu-MT was significantly higher in LEC rats than in Fischer rats. However, its excretion was not responded to the gross accumulation of hepati MT. 3.Relation between deposition of Cu and MT,and onset of hepatitis. MT in the LEC liver showed a preventive action against the lipidperoxidation stimulated by Fe-NTA.Accordingly, until the onset of hepatits, MT plays as a scavenger, When LEC rats were fed a Cu deficient diet, hepatitis was not occured at around 120 days after birth. Accordingly, the onset of hepatitis is related closely to the Cu level in food. 4.Therapy of hepatitis, and liver cancer. Chelator, tetrathiomolybdate (TTM) was effective for the therapy of hepatitis. Now, survived rats from hepatitis by the treatment are maintained for the further occurance of liver cancer.
|