| Budget Amount *help |
¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
Fiscal Year 2015: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2013: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
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| Outline of Final Research Achievements |
Acyl glucuronides (AGs) may be related with the toxicity of carboxyl acid drugs, because AGs covalently bind to endogenous proteins owing to potential reactivity. However, the theory remains controversial. In this study, first, the changes in the mRNA and protein expression levels of IL-8 and MCP-1 induced by the treatment of human peripheral blood mononuclear cells (PBMCs) with several AG of NSAIDs. Second, short half-lives, peptide adducts and immunostimulation were observed in AGs of all withdrawn drugs. Third, responsibility of zomepirac acyl glucuronide (ZP-AG) for renal toxicity by ZP was investigated by in vivo studies. ZP-induced kidney injury mouse model was established by pretreatment with an esterase inhibitor and a glutathione synthesis inhibitor. Fourth, the inhibition of diclofenac (DCF)-AG production by the (-)-borneol (BOR) pretreatment alleviated DIC-induced liver injury in mouse. DIC-AG was involved in the pathogenesis of DIC-induced liver injury.
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