Characteristics of troponins as myocardial damage biomarkers in cynomolgus monkeys
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概要
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Recently, troponin T (TnT) and troponin I (TnI) have been reported as suitable biomarkers of myocardial injury for pre-clinical toxicity studies. The purpose of the present study was to investigate the characteristics of troponins as myocardial damage biomarkers in cynomolgus monkeys. Initially, tissue distribution of biomarkers was investigated in nine organs (including the heart, liver, and kidneys) collected from naive cynomolgus monkeys. The results showed that TnT and TnI were distributed specifically in the heart, and were not detected in other tissues. Secondly, changes in blood biomarker levels and histopathological changes in cardiac tissue were investigated following myocardial injury induced by con-comitant administration of isoproterenol (ISO) and vasopressin (VASO). Compared with pre-dosing, TnT and TnI were markedly increased in the ISO+VASO groups, in which severe histopathological changes including necrosis and vacuolation of muscle fibers were observed. In order to investigate the relationship of biomarker levels with the severity of myocardial injury, Spearman's correlation coefficient was calculated between C_<max> and AUC and necrosis and vacuolation scores in the heart. A high correlation between necrosis and vacuolation in the heart and TnT and TnI levels was noted. These results suggest that TnT and TnI possess high sensitivity and specificity for myocardial injury in cynomolgus monkeys, and are useful biomarkers for detection of drug-induced myocardial injury in cynomolgus monkeys.
- 2009-12-01
著者
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FUKUZAKI Koichiro
Shin Nippon Biomedical Laboratories (SNBL), Ltd.
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NAGATA Ryoichi
Shin Nippon Biomedical Laboratories (SNBL), Ltd.
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Maeda Hiroshi
Shin Nippon Biomedical Laboratories Ltd. Drug Safety Research Laboratories
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Maeda Hiroshi
Shin Nippon Biomedical Laboratories Ltd.
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Nagata Ryoichi
Shin Nippon Biomedical Laboratories Ltd. Drug Safety Research Laboratories
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Nagata Ryoichi
Shin Nippon Biomedical Laboratories (snbl) Ltd.
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Nagata Ryoichi
Shin Nippon Biomedical Laboratories Ltd.
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KADOKURA HIDETOMI
Shin Nippon Biomedical Laboratories Ltd.
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Nakama Kazuhiro
Shin Nippon Biomedical Laboratories, Ltd.
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Minomo Hirofumi
Shin Nippon Biomedical Laboratories, Ltd., Drug Safety Research Laboratories
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Torikai Yusuke
Shin Nippon Biomedical Laboratories, Ltd., Drug Safety Research Laboratories
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Furukawa Tomohiro
Shin Nippon Biomedical Laboratories, Ltd., Drug Safety Research Laboratories
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Uchino Hiroshi
Shin Nippon Biomedical Laboratories, Ltd., Drug Safety Research Laboratories
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Kamenosono Takeshi
Shin Nippon Biomedical Laboratories, Ltd., Drug Safety Research Laboratories
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Sukamoto Takayuki
Shin Nippon Biomedical Laboratories, Ltd., Drug Safety Research Laboratories
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Fukuzaki Koichiro
Shin Nippon Biomedical Laboratories Ltd. Drug Safety Research Laboratories
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Fukuzaki Koichiro
Shin Nippon Biomedical Laboratories (snbl) Ltd.
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Fukuzaki Koichiro
Shin Nippon Biomedical Laboratories Ltd. Drug Safety Research Laboratories (snbl Dsr)
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Kamenosono Takeshi
Shin Nippon Biomedical Laboratories Ltd. Drug Safety Research Laboratories
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Fukuzaki Koichirou
Snbl Usa Ltd.
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Uchino Hiroshi
Shin Nippon Biomedical Laboratories Ltd. Drug Safety Research Laboratories
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Torikai Yusuke
Shin Nippon Biomedical Laboratories Ltd. Drug Safety Research Laboratories
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Nakama Kazuhiro
Shin Nippon Biomedical Laboratories Ltd. Drug Safety Research Laboratories
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Nakama Kazuhiro
Shin Nippon Biomedical Laboratories Ltd.
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Minomo Hirofumi
Shin Nippon Biomedical Laboratories Ltd. Drug Safety Research Laboratories
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Sukamoto Takayuki
Shin Nippon Biomedical Laboratories Ltd. Drug Safety Research Laboratories
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Nagata Ryoichi
Toxicology Division Shin Nippon Biomedical Laboratories
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Kadokura Hidetomi
Shin Nippon Biomedical Laboratories Ltd. Drug Safety Research Laboratories
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Furukawa Tomohiro
Shin Nippon Biomedical Laboratories Ltd. Drug Safety Research Laboratories
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Nagata Ryoichi
Shin Nippon Biomedical Laboratories Ltd. Jpn
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Nagata Ryoichi
Shin Nippon Biomedical Lab. Ltd.
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Maeda Hiroshi
Shin Nippon Biomedical Laboratories Co. Ltd.
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