Risk assessment and mechanistic analysis of adverse reactions of the acyl glucuronides.
| Project/Area Number |
25293037
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Partial Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Medical pharmacy
|
|---|
| Research Institution | Nagoya University |
|---|
Principal Investigator |
Yokoi Tsuyoshi 名古屋大学, 医学(系)研究科(研究院), 教授 (70135226)
|
|---|
| Project Period (FY) |
2013-04-01 – 2016-03-31
|
| Project Status |
Completed (Fiscal Year 2015)
|
| 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)
|
|---|
| Keywords | グルクロン酸転移酵素 / アシルグルクロニド / ジクロフェナク / ゾメピラク / 医薬品副作用 / 加水分解酵素阻害薬 / グルタチオン合成阻害薬 / 動物モデル / 加水分解酵素 / アシルグルクロナイド / UGT1A3 / UGT2B7 |
|---|
| 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 Second, short half-lives, peptide adducts and immunostimulation were observed in AGs of all withdrawn drugs.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.
|
Report
(4 results)
Research Products
(31 results)
-
-
-
-
[Journal Article] Toxicological evaluation of acyl glucuronides utilizing half-lives, peptide adducts, and immunostimulation assays.2015
Author(s)
Atsushi Iwamura, Masahito Ito, Hideaki Mitsui, Jun Hasegawa, Keigo Kosaka, Ichiro Kino, Minoru Tsuda, Miki Nakajima, Tsuyoshi Yokoi and Toshiyuki Kume.
-
Journal Title
Toxicol. In Vitro
Volume: 30
Issue: 1
Pages: 241-249
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
