Sunao Manabe
Daiichi Sankyo
GeneInternal medicineEndocrinologyPathologyGene expressionMolecular biologyChemistryIn vivoPhenobarbitalClofibrateToxicityNecrosisCytochrome P450GlutathioneBiochemistryBioinformaticsMedicineBiologyToxicogenomicsPharmacology
Publications 117
#1Naoki Kiyosawa (Daiichi Sankyo)H-Index: 17
#2Sunao Manabe (Daiichi Sankyo)H-Index: 17
Pharmaceutical companies continuously face challenges to deliver new drugs with true medical value. RD it is the basis for identifying the right drug target and creating a drug concept with true medical value. Our understanding of the pathophysiological mechanisms of disease animal models can also be improved; it can thus support rational extrapolation of animal experiment results to clinical settings. The Systems Biology approach, which leverages publicly available transcriptome data, is useful...
3 CitationsSource
#1Shusuke Yamauchi (Daiichi Sankyo)H-Index: 2
#2Naoki Kiyosawa (Daiichi Sankyo)H-Index: 17
Last. Atsushi Sanbuissho (Daiichi Sankyo)H-Index: 11
view all 9 authors...
Hepatic transcriptome and proteome responses against glutathione depletion were investigated by Affymetrix GeneChip Microarray and 2-dimensional gel electrophoresis (2D-DIGE), followed by MALDI-TOF–MS analysis and utilizing a glutathione-depleted rat model treated with diethyl maleate (DEM). Hepatic glutathione content decreased to 1.29 μmol/g liver (25.5% compared to control) after DEM treatment, and there were no apparent hepatotoxic signs estimated by blood chemistry examinations. A total of ...
15 CitationsSource
#1Hisakuni Obayashi (Daiichi Sankyo)H-Index: 1
#2Yoshikazu Nezu (Daiichi Sankyo)H-Index: 2
Last. Atsushi Sanbuissho (Daiichi Sankyo)H-Index: 11
view all 9 authors...
3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are associated with adverse skeletal muscle toxicity, but the underlying mechanism remains unclear. To investigate the pathological mechanism of statin-induced myotoxicity, cerivastatin (20 ppm; corresponding to 2 mg/kg/day) was dietarily administered to young male F344 rats for 10 days, and time-course clinical observations, measurement of plasma creatine kinase activity, and light and electron microscopy of type I fiber-predo...
19 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
view all 10 authors...
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
#1Kazunori Fujimoto (Daiichi Sankyo)H-Index: 9
#2Hiroyuki Kishino (Daiichi Sankyo)H-Index: 1
Last. Atsushi Sanbuissho (Daiichi Sankyo)H-Index: 11
view all 5 authors...
Abstract Glutathione plays an important role as not only a scavenger of reactive oxygen species but also in the conjugation or detoxification of electrophilic reactive metabolites, which has been thought to be one of the causes for idiosyncratic drug toxicity (IDT). Therefore, toxic responses to the reactive metabolites have been expected to be expressed more strongly in a glutathione-depleted condition. In the present study, we attempted to establish an in vitro cytotoxicity assay method to eva...
7 CitationsSource
#1Makoto Takei (Daiichi Sankyo)H-Index: 3
#2Yosuke Ando (Daiichi Sankyo)H-Index: 17
Last. Lining Guo (Durham University)H-Index: 27
view all 15 authors...
Ethylene glycol monomethyl ether (EGME) is a widely used industrial solvent known to cause adverse effects to human and other mammals. Organs with high metabolism and rapid cell division, such as testes, are especially sensitive to its actions. In order to gain mechanistic understanding of EGME-induced toxicity, an untargeted metabolomic analysis was performed in rats. Male rats were administrated with EGME at 30 and 100 mg/kg/day. At days 1, 4, and 14, serum, urine, liver, and testes were colle...
35 CitationsSource
#1Jun Hirao (Daiichi Sankyo)H-Index: 4
#2Noriyo Niino (Daiichi Sankyo)H-Index: 8
Last. Masugi Nishihara (UTokyo: University of Tokyo)H-Index: 40
view all 11 authors...
The secretory profile of growth hormone (GH) is sexually dimorphic in rats. In male transgenic (TG) rats expressing human GH (hGH) that we generated, the circulating levels of both hGH and endogenous GH are flattened with no male-type pulsatility. To elucidate the regulatory role of episodic GH profile on the liver, the hepatic transcriptome of male TG rats at the middle of the light and dark phases was characterized by genome-wide analyses as compared with that of male wild-type (WT) rats. Tran...
4 CitationsSource
#1Naoki Kiyosawa (Daiichi Sankyo)H-Index: 17
#2Sunao ManabeH-Index: 17
Last. Atsushi SanbuisshoH-Index: 11
view all 4 authors...
A systems-level understanding of molecular perturbations is crucial for evaluating chemical-induced toxicity risks appropriately, and for this purpose comprehensive gene expression analysis or toxicogenomics investigation is highly advantageous. The recent accumulation of toxicity-associated gene sets (toxicogenomic biomarkers), enrichment in public or commercial large-scale microarray database and availability of open-source software resources facilitate our utilization of the toxicogenomic dat...
21 CitationsSource
#1Shingo Arakawa (Daiichi Sankyo)H-Index: 11
#2Takanori MaejimaH-Index: 6
Last. Wataru TakasakiH-Index: 8
view all 10 authors...
A specific substrate to Mu class glutathione S-transferase (GST), 1,2-dichloro-4-nitrobenzene (DCNB), was administered to mice with a disrupted GST Mu 1 gene (Gstm1-null mice) to investigate the in vivo role of murine Gstm1 in toxicological responses to DCNB. A single oral administration of DCNB at doses of 500 and 1000 mg/kg demonstrated a marked increase in blood methemoglobin (MetHB) in Gstm1-null mice but not in wild-type mice. Therefore, Gstm1-null mice were considered to be more predispose...
14 CitationsSource
#1Naoki Kiyosawa (Daiichi Sankyo)H-Index: 17
#2Sunao Manabe (Daiichi Sankyo)H-Index: 17
Last. Takashi Yamoto (Daiichi Sankyo)H-Index: 15
view all 4 authors...
Toxicogenomics data sets on rat livers covering 118 compounds were subjected to inference of a gene set-level, not individual gene-level, network structure. Expression changing levels for 58 gene sets was used for network inference with a Gaussian graphical model algorithm. The established network contained reasonable relationships, such as ones between the blood glucose level and glycolysis-related genes or the blood transaminase level and cellular injury-related genes, indicating that the gene...
8 CitationsSource