Takeshi Susukida
University of Toyama
Induced pluripotent stem cellInternal medicineEndocrinologyGenetically modified mouseTransporterCytotoxic T cellChemistryHuman leukocyte antigenEffluxIn vitroImmunologyIn vivoHepatocyteLiver injuryOrganic anion-transporting polypeptideBilirubinCholestasisBile acidDrugTaurocholic acidBile Salt Export PumpToxicityMultidrug resistance-associated protein 2BiochemistryMedicineBiologyImmune systemPharmacology
13Publications
5H-index
78Citations
Publications 12
Newest
#1Takeshi Susukida (University of Toyama)H-Index: 5
#1Takeshi Susukida (University of Toyama)
Last. Kousei Ito (Chiba University)H-Index: 29
view all 6 authors...
Various types of transgenic mice carrying either class I or II human leukocyte antigen (HLA) molecules are readily available, and reports describing their use in a variety of studies have been publ...
1 CitationsSource
#1Moemi Kawaguchi (Chiba University)H-Index: 2
#2Takumi NukagaH-Index: 2
Last. Kousei Ito (Chiba University)H-Index: 29
view all 10 authors...
Abstract Drug-induced liver injury (DILI) can cause hepatic failure and result in drug withdrawal from the market. It has host-related and compound-dependent mechanisms. Preclinical prediction of DILI risk is very challenging and safety assessments based on animals inadequately forecast human DILI risk. In contrast, human-derived in vitro cell culture-based models could improve DILI risk prediction accuracy. Here, we developed and validated an innovative method to assess DILI risk associated wit...
3 CitationsSource
#1Yoko Sakai (Nagoya City University)H-Index: 2
#2Takahiro Iwao (Nagoya City University)H-Index: 10
Last. Tamihide Matsunaga (Nagoya City University)H-Index: 17
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Abstract Cholestatic drug-induced liver injury (DILI) is a type of hepatotoxicity. Its underlying mechanisms are dysfunction of bile salt export pump (BSEP) and multidrug resistance-associated protein 2/3/4 (MRP2/3/4), which play major roles in bile acid (BA) excretion into the bile canaliculi and blood, resulting in accumulation of BAs in hepatocytes. The sandwich-cultured hepatocyte (SCH) model can simultaneously analyze hepatic uptake and biliary excretion. Therefore, we investigated whether ...
3 CitationsSource
#1Binbin Song (Chiba University)H-Index: 3
#2Shigeki Aoki (Chiba University)H-Index: 7
Last. Kousei Ito (Chiba University)H-Index: 29
view all 5 authors...
: Genome-wide association studies indicate that several idiosyncratic adverse drug reactions are highly associated with specific human leukocyte antigen (HLA) alleles. For instance, abacavir, a human immunodeficiency virus reverse transcriptase inhibitor, induces multiorgan toxicity exclusively in patients carrying the HLA-B*57:01 allele. However, the underlying mechanism is unclear due to a lack of appropriate animal models. Previously, we developed HLA-B*57:01 transgenic mice and found that to...
9 CitationsSource
#1Takeshi Susukida (Chiba University)H-Index: 5
#2Shigeki Aoki (Chiba University)H-Index: 7
Last. Kousei Ito (Chiba University)H-Index: 29
view all 8 authors...
Immune-mediated idiosyncratic drug toxicity (IDT) is a rare adverse drug reaction, potentially resulting in death. Although genome-wide association studies suggest that the occurrence of immune-mediated IDT is strongly associated with specific human leukocyte antigen (HLA) allotypes, these associations have not yet been prospectively demonstrated. In this study, we focused on HLA-B*57:01 and abacavir (ABC)-induced immune-mediated IDT, and constructed transgenic mice carrying chimeric HLA-B*57:01...
5 CitationsSource
#1Yoko SakaiH-Index: 2
#2Takahiro IwaoH-Index: 10
Last. Tamihide MatsunagaH-Index: 17
view all 8 authors...
Source
#1Kumiko Oizumi (Chiba University)H-Index: 3
#2Shuichi Sekine (Chiba University)H-Index: 18
Last. Kousei Ito (Chiba University)H-Index: 29
view all 5 authors...
Abstract Inhibition of bile salt export pump (BSEP) causes hepatic accumulation of toxic bile acid (BA), leading to hepatocyte death. We reported a sandwich-cultured hepatocyte (SCH)–based model that can estimate potential cholestatic compounds by assessing their ability to induce hepatotoxicity in combination with a titrated amount of human 12 BA species. However, there is little information about the specific BAs responsible for hepatotoxicity, when BSEP is inhibited. This study measured the a...
11 CitationsSource
#1Takeshi Susukida (Chiba University)H-Index: 5
#2Shuichi Sekine (Chiba University)H-Index: 18
Last. Kousei Ito (Chiba University)H-Index: 29
view all 7 authors...
Abstract Bile acid (BA) retention within hepatocytes is an underlying mechanism of cholestatic drug-induced liver injury (DILI). We previously developed an assay using sandwich-cultured human hepatocytes (SCHHs) to evaluate drug-induced hepatocyte toxicity accompanying intracellular BA accumulation. However, due to shortcomings commonly associated with the use of primary human hepatocytes (e.g., limited availability, lot-to-lot variability, and high cost), we examined if the human hepatic stem c...
17 CitationsSource
#1Takeshi SusukidaH-Index: 5
#2Shuichi SekineH-Index: 18
view all 7 authors...
Bile acid (BA) retention within hepatocytes is an underlying mechanism of cholestatic drug-induced liver injury (DILI). We previously developed an assay using sandwich-cultured human hepatocytes (SCHHs) to evaluate drug-induced hepatocyte toxicity accompanying intracellular BA accumulation. However, due to shortcomings commonly associated with the use of primary human hepatocytes (e.g., limited availability, lot-to-lot variability, and high cost), we examined if the human hepatic stem cell line,...
#1Takeshi Susukida (Chiba University)H-Index: 5
#2Shuichi Sekine (Chiba University)H-Index: 18
Last. Kousei Ito (Chiba University)H-Index: 29
view all 5 authors...
Drug-induced liver injury (DILI) is of concern to the pharmaceutical industry and reliable preclinical screens are required. Previously, we established an in vitro bile acid-dependent hepatotoxicity assay that mimics cholestatic DILI in vivo. Here, we confirmed that this assay can predict cholestatic DILI in clinical situations by comparing in vitro cytotoxicity data with in vivo risk. For 38 drugs, the frequencies of abnormal increases in serum alkaline phosphatase (ALP), transaminases, gamma g...
21 CitationsSource