PROTEIN EXPRESSION ANALYSIS OF RAT TESTES INDUCED TESTICULAR TOXICITY WITH SEVERAL REPRODUCTIVE TOXICANTS
スポンサーリンク
概要
- 論文の詳細を見る
The utilization of safety biomarkers to predict the possibility of compound-related toxicity provides several advantages for drug discovery and development, especially at an early stage. The objectives of this study were to investigate the effects of male reproductive toxicants on protein expression profiles in the rat testes and to identify potential biomarker candidates. Four well-known reproductive toxicants, ethylene glycol monomethyl ether (EGME), cyclophosphamide (CP), sulfasalazine (SASP) and 2,5-hexanedione (2,5-HD), were administered to male rats in a single dose, and protein expression profiles were investigated after 24 hr by two-dimensional gel electrophoresis (2DE). Histopathological examination of the testes and serum concentration analysis were also performed. From the results of the comparison of 2D-gels among different doses of a compound and among compounds, 52, 20, 24 and 111 spots were nominated as differentially expressed spots with EGME, CP, SASP and 2,5-HD treatments, respectively. Several spermatogenesis-involved proteins were identified, including glutathione S-transferase (GST), testis-specific heat shock protein 70-2 (HSP70-2), glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and phosphatidylethanolamine-binding protein (PEBP). Some of them were altered by more than one compound. In summary, remarkable histopathological findings were observed only in the EGME high-dose group, and most of the protein changes were detected before histopathological changes occurred. Therefore, the proteins identified in this study could potentially serve as biomarkers to evaluate male reproductive toxicity at an early stage of drug discovery and development.
- 日本トキシコロジー学会の論文
- 2005-05-25
著者
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HORII Ikuo
Worldwide Safety Sciences, Nagoya Laboratories, Pfizer Global Research and Development, Pfizer Japan
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Yamamoto Toshinori
Drug Safety Research & Development Pfizer Global Research & Development Nagoya Laboratories
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Yamamoto T
Showa Univ. Tokyo Jpn
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Yamamoto Toshinori
Department Of Biochemical Toxicology School Of Pharmaceutical Sciences Showa University
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Yamada Hiroshi
worldwide safety sciences
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Horii Ikuo
Showa Univ. (department Of Biochemical Toxicology School Of Pharmaceutical Sciences)
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Horii I
Drug Safety Research And Development Pfizer Global Research And Development Nagoya Laboratories. Pfi
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Horii Ikuo
Pfizer Global Research & Development Nagoya Laboratories Pfizer Inc.
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YAMAMOTO Toshinori
Worldwide Safety Sciences, Pfizer Global Research & Development, Nagoya Laboratories, Pfizer Inc.
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KIKKAWA Rie
Worldwide Safety Sciences, Pfizer Global Research & Development, Nagoya Laboratories, Pfizer Inc.
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FUKUSHIMA Tamio
Worldwide Safety Sciences, Global Research & Development, Nagoya Laboratories, Pfizer Inc.
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Kikkawa Rie
Worldwide Safety Sciences Pfizer Global Research And Development Nagoya Laboratories Pfizer Inc.
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Kikkawa Rie
Worldwide Safety Sciences Global Research & Development Nagoya Laboratories Pfizer Inc.
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Yamada Hiroshi
Drug Safety Research & Development Pfizer Global Research & Development Nagoya Laboratories
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Fukushima Tamio
Drug Safety Research And Development Nagoya Laboratories Pfizer Japan Inc.
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Fukushima Tamio
Worldwide Safety Sciences Pfizer Global Research & Development Nagoya Laboratories Pfizer Inc.
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Fukushima Tamio
Pfizer Global Research & Development Toxicology Nagoya Laboratoreis
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Kikkawa Rie
Pfizer Global Research & Development Toxicology Nagoya Laboratoreis
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Horii Ikuo
Worldwide Safety Sciences Pgrd Nagoya Laboratories Pfizer Inc.
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Yamamoto Toshinori
Departments Of Clinical Pharmacy And Pharmacognosy School Of Pharmaceutical Sciences Showa Universit
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Horii Ikuo
Worldwide Safety Sciences
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Horii Ikuo
Worldwide Safety Sciences Pfizer Global Research & Development Nagoya Laboratories Pfizer Inc.
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Horii Ikuo
Biochemical Toxicology School Of Pharmaceutical Sciences Showa University
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Fukushima Tamio
Biochemical Toxicology School Of Pharmaceutical Sciences Showa University
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Yamada Hiroshi
Worldwide Safety Sciences Pfizer Global Research And Development Nagoya Laboratories Pfizer Japan In
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Yamamoto Toshinori
Department Of Pharmacology Medical College Of Oita
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