Investigation of the "thiamine deficiency hypothesis" as a mechanism of metronidazole-induced encephalopathy

2022 Fiscal Year Final Research Report

• Project/Area Number: 18K14992
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Musashino University
• Principal Investigator: Yamagishi Yoshiaki 武蔵野大学, 薬学部, 助教 (30805255)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Keywords: チアミン / メトロニダゾール / チアミントランスポーター / メトロニダゾール誘発性脳症 (MIE)

Outline of Final Research Achievements

In this study, the mechanism of metronidazole (MTZ)-induced encephalopathy was investigated focusing on the possibility that MTZ, with a substructure similar to thiamine, inhibits thiamine transporters to decrease thiamine uptake into the brain and induce the encephalopathy (“thiamine deficiency hypothesis”). The effects of MTZ near clinical concentrations on the cellular uptake and the transcellular transport of thiamine were investigated in vitro and the results suggested that MTZ may not inhibit the absorption of thiamine from the gastrointestinal tract and its transport into brain tissue. However, an increased cellular uptake of thiamine was detected with relatively high concentrations of MTZ.

Free Research Field

薬物動態学

Academic Significance and Societal Importance of the Research Achievements

近年、MTZ誘発性脳症は増加傾向にあり、本研究は当該脳症の発症メカニズムの解明に迫る検討を行った。消化管上皮細胞層におけるチアミンの細胞内への取り込みおよび細胞層の透過過程において、MTZが何らかの影響を及ぼしている可能性を示すことができた。これらの結果は、MTZ誘発性脳症の発症メカニズムの解明において有力な手掛かりとなる情報である。今後、当該脳症の発症メカニズムについてさらに詳細な解明を進めることで、臨床におけるMTZの適正使用に資する有用な情報を提供することができると考える。