Shingo Arakawa
Daiichi Sankyo
GeneGene targetingIsozymeCircadian rhythmInternal medicineEnzyme inducerEndocrinologyGenotypeCYP2E1Molecular biologyDifference gel electrophoresisEnzymeChemistryToxicokineticsImmunologyIn vivoWestern blotRatónAcetaminophenClofibrateCentrilobular necrosisDiet-induced obeseSpleenThioacetamideGlutathione S-Transferase MuToxicityP450 monooxygenaseMale ratsNecrosisGlutathioneGeneticsBiochemistryMedicineDose–response relationshipTranscription factorBiologyProtein kinase APharmacologyCytosol
24Publications
11H-index
553Citations
Publications 24
Newest
#1Ryota Shizu (University of Shizuoka)H-Index: 4
Last. Kouichi Yoshinari (University of Shizuoka)H-Index: 29
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Long-term administration of some antiepileptic drugs often increases blood lipid levels. In this study, we investigated its molecular mechanism by focusing on the nuclear receptors constitutive active/androstane receptor (CAR) and peroxisome proliferator-activated receptor α (PPARα), which are key transcription factors for enzyme induction and lipid metabolism, respectively, in the liver. Treatment of mice with the CAR activator phenobarbital, an antiepileptic drug, increased plasma triglyceride...
1 CitationsSource
#1Yuki Kishino (Daiichi Sankyo)H-Index: 3
#2Tomoko Hasegawa (Daiichi Sankyo)H-Index: 3
Last. Kazuhiko Mori (Daiichi Sankyo)H-Index: 9
view all 6 authors...
: A high incidence of positive results is obtained with in vitro genotoxicity tests, which do not correlate with the in vivo negative results in many cases. To address this issue, the metabolic profile of rat liver 9000 × g supernatant fraction (S9) pretreated with phenobarbital (PB) and 5,6-benzoflavone (BNF) was characterized. Furthermore, the in vitro micronucleus tests of 10 compounds were performed with PB-BNF-induced rat S9. PB-BNF increased cytochrome P450 (CYP) activity and CYP1A1, CYP1A...
2 CitationsSource
#1Yusuke Ogitani (Daiichi Sankyo)H-Index: 8
#2Tetsuo Aida (Daiichi Sankyo)H-Index: 6
Last. Toshinori Agatsuma (Daiichi Sankyo)H-Index: 12
view all 16 authors...
Purpose: An anti-HER2 antibody–drug conjugate with a novel topoisomerase I inhibitor, DS-8201a, was generated as a new antitumor drug candidate, and its preclinical pharmacologic profile was assessed. Experimental Design:In vitro and in vivo pharmacologic activities of DS-8201a were evaluated and compared with T-DM1 in several HER2-positive cell lines and patient-derived xenograft (PDX) models. The mechanism of action for the efficacy was also evaluated. Pharmacokinetics in cynomolgus monkeys an...
210 CitationsSource
#1Makoto Shirai (Daiichi Sankyo)H-Index: 4
#2Shingo Arakawa (Daiichi Sankyo)H-Index: 11
Last. Kiyonori Kai (Daiichi Sankyo)H-Index: 7
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We previously reported that thioacetamide (TA)-induced hepatocellular necrosis was attenuated in mice fed a high-fat diet (HFD mice) compared with mice fed a normal rodent diet (ND mice). In this study, we investigated whether p38 mitogen-activated protein kinase (p38 MAPK) was involved in this attenuation. Western blot analysis revealed that hepatic phosphorylated p38 MAPK protein decreased at 8 and 24 hours (hr) after TA dosing in the HFD mice, while it decreased only at 24 hr in the ND mice i...
2 CitationsSource
#1Isao Igarashi (Daiichi Sankyo)H-Index: 3
#2Takanori Maejima (Daiichi Sankyo)H-Index: 6
Last. Atsushi Sanbuissho (Daiichi Sankyo)H-Index: 11
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Abstract Gap junctional intercellular communication (GJIC), by which glutathione (GSH) and inorganic ions are transmitted to neighboring cells, is recognized as being largely involved in toxic processes of chemicals. We examined acetaminophen (APAP)-induced hepatotoxicity clinicopathologically using male wild-type mice and mice lacking the gene for connexin32, a major gap junction protein in the liver [knockout (Cx32KO) mice]. When APAP was intraperitoneally administered at doses of 100, 200, or...
18 CitationsSource
#1Makoto Shirai (Daiichi Sankyo)H-Index: 4
#2Shingo Arakawa (Daiichi Sankyo)H-Index: 11
Last. Munehiro Teranishi (Daiichi Sankyo)H-Index: 11
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To assess modification of thioacetamide-induced hepatotoxicity in mice fed a high-fat diet, male C57BL/6J mice were fed a normal rodent diet or a high-fat diet for 8 weeks and then treated once intraperitoneally with thioacetamide at 50 mg/kg body weight. At 24 and 48 hours after administration, massive centrilobular hepatocellular necrosis was observed in mice fed the normal rodent diet, while the necrosis was less severe in mice fed the high-fat diet. In contrast, severe swelling of hepatocyte...
8 CitationsSource
Introduction: Glutathione S-transferases (GSTs) are Phase II drug-metabolizing enzymes that catalyze the conjugation of electrophilic compounds to glutathione. This reaction generally detoxifies reactive metabolites of xenobiotics, such as drugs and environmental chemicals, and therefore, GSTs are considered toxicologically important enzymes. Human GST genes display genetic polymorphisms, and the impact of null genotypes of GST Mu 1 (GSTM1) and GST Theta 1 (GSTT1) have been extensively studied. ...
7 CitationsSource
#1Shingo Arakawa (Daiichi Sankyo)H-Index: 11
#2Takanori Maejima (Daiichi Sankyo)H-Index: 6
Last. Yasushi Yamazoe (Tohoku University)H-Index: 65
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: We investigated the role of glutathione S-transferases Mu 1 (GSTM1) in acetaminophen (APAP)-induced hepatotoxicity using Gstm1-null mice. A single oral administration of APAP resulted in a marked increase in plasma alanine aminotransferase accompanied by hepatocyte necrosis 24 hr after administration in wild-type mice, but its magnitude was unexpectedly attenuated in Gstm1-null mice. Therefore, it is suggested that Gstm1-null mice are resistant to APAP-induced hepatotoxicity. To examine the me...
15 CitationsSource
We investigated the impact of glutathione transferases Mu 1 ( GSTM1 )- and glutathione transferase Theta 1 ( GSTT1 )-null genotypes on hepatic GST activities in humans and compared the results with those of Gstm1 - and Gstt1 -null mice. In liver with GSTM1 / Gstm1 -null genotype, GST activity toward p -nitrobenzyl chloride (NBC) was significantly decreased in both humans and mice. In addition, in liver with GSTT1 / Gstt1 -null genotype, GST activity toward dichloromethane (DCM) was significantly...
9 CitationsSource
#1Jun Hirao (Daiichi Sankyo)H-Index: 4
#2Masatoshi Nishimura (Daiichi Sankyo)H-Index: 1
Last. Yuji Mori (UTokyo: University of Tokyo)H-Index: 51
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The present study was designed to fully uncover sex and circadian modulatory effects on rat liver. Hepatic transcriptome analyses were performed at 4 hr intervals of a day-night cycle using young adult male and female rats. Sexually dimorphic genes, which were identified by a cross-sex comparison of time series data, included representative sex-predominant genes such as male- or female-predominant cytochrome P450 subfamilies (Cyp2c11, Cyp2c12, Cyp2c13, and Cyp3a2), sulfotransferases, and glutath...
23 CitationsSource