| Project/Area Number |
06672155
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Physical pharmacy
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| Research Institution | Chiba University |
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Principal Investigator |
HORIE Toshiharu Chiba University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (90120154)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1995: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1994: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | oxidative stress / lipid peroxidation / hepatotoxicity / hepatocyte / chemiluminescence / acetaminophen / glutathione / naproxen |
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| Research Abstract |
In order to verify the contribution of the active oxygens to the drug-induced hepatotoxicity, it is very important to detect the active oxygens generated during the drug metabolism. Chemiluminescence produced from the active oxygens, glutathione, fluorescent substances, high molecular weight protein aggregates and thiobarbituric acid reactive substances were used to study the drug-induced oxidative stress in perfused rat liver, isolated rat hepatocyte and mitochondria. 1. The ultra weak chemiluminescence was detected in the homogenates of rat liver perfused with acetaminophen solution.
The high molecular weight protein aggregates were foromed in the liver perfused with a cetaminophen and the reduced glutathione decreased in the liver. The oxidized glutathione increased slightly in the rat liver perfused with naproxen solution. 2. The ultra weak chemiluminescence was detected in the isolated hepatocytes with acetaminophen. Naproxen also produced the chemiluminescence in the hepatocyte suspension and increased the ratio of oxidized glutathione to the total glutathione. Ethacrynic acid induced lipid peroxidation in the hepatocytes due to the oxidative metabolism. 3. The ultra weak chemiluminescence was detected in the mitochondria with doxorubicin and the origins of the chemiluminescence were found to be singlet oxygen and excited carbonyls. Phosphatidylcholine hydroperoxide was detected in the heart homogenates of doxorubicin administered mouse using the chemiluminescence-HPLCsystem.
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