The impacts of blood bilirubin levels on calcineurine-inhibitor concentrations in the brain to develop neurotoxicity in Rats.

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461906
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Tohoku University
• Principal Investigator: Sato Kazushige 東北大学, 医学系研究科, 大学院非常勤講師 (40375043)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: カルシニューリンインヒビター / 中枢神経毒性 / 白質脳症 / 脳内移行 / ビリルビン

Outline of Final Research Achievements

We investigated the correlation between neurotoxicity and the intracerebral concentration of tacrolimus using Rats. The levels of the whole blood and the corresponding intracerebral concentration were evaluated. The threshold concentration of tacrolimus in the brain resulting in neurotoxic events was therefore estimated approximately 870 ng/g. Using a linear correlation between the whole blood and intracerebral concentrations of tacrolimus, the pharmacological threshold for the whole blood level was estimated as 28.6 ng/mL. Next, we investigated the effects of higher blood bilirubin levels to the intracerebral concentrations using galactosamine-induced liver failure rats. There was very strong correlations between the blood bilirubin levels and the intracerebral concentration of tacrolimus. Thus, the prolonged higher levels of bilirubin may alter capillary endothelial cells of blood-brain-barrier, and consequently lead to tacrolimus-associated cytotoxic injuries in the brain.

Free Research Field

移植免疫学