| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Research Abstract |
In general, drugs containing carboxylic acid are metabolized to acyl-glucuronide (AG) forms, which are considered to cause various toxicities including hepatotoxicity and anaphylaxis, in body. Therefore, it is conceivable that the enzymes hydrolyzing AG can attenuate the drug-induced toxicities. In this study, the enzyme responsible for AG hydrolysis was identified and its function was clarified. By the purification from human livers, alpha/beta hydrolase domain containing 10 (ABHD10) was identified as an AG hydrolase. ABHD10 could hydrolyze various kinds of AG such as AGs of mycophenolic acid, probenecid, and diclofenac. For in vivo study, mice pre-treated with an ABHD10 inhibitor showed the significantly higher AG plasma concentration compared with non-treated mice after an oral administration of diclofenac. Thus, it was clarified in vivo that ABHD10 can affect the plasma concentration of AGs. ABHD10 may play important roles for attenuation of the AGs-induced toxicity.
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