TOXICOLOGICAL RESPONSE OF RATS TO A NOVEL MONOAMINE OXIDASE TYPE-A INHIBITOR, (5R)-3-[2-((1S)-3-CYANO-1-HYDROX-YPROPYL)BENZOTHIAZOL-6-YL]-5-METHOXYMETHYL-2-OXAZOLIDI-NONE (E2011), ORALLY ADMINISTERED FOR 13 WEEKS
スポンサーリンク
概要
- 論文の詳細を見る
(5R)-3-[2-((1S)-3-cyano-1-hydroxypropyl)benzothiazol-6-yl]-5-methoxymethyl-2-oxazolidinone (E2011) is a novel monoamine oxidase type-A (MAD-A) inhibitor. In order to assess toxicological profiles of E2011, doses of 0 (as controls), 30, 100 mg/kg of E2011 were administered to male and female Sprague-Dawley rats once a day for 13 weeks orally by gavage. No mortality or any toxic signs except salivation occurred due to E2011 treatment. Decreased body weight gain and food consumption, increases of alkaline phosphatase and increases of liver weight were the major treatment-related findings observed predominantly in the 100 mg/kg group. Histological examination revealed nuclear enlargement of hepatocytes with appearance of altered cell foci in some cases, and acinar atrophy in Harderian glands in the 100 mg/kg group. Since the histopathological findings in the liver were indicative of an ongoing carcinogenic process, glutathione S-transferase placental form (GST-P) positive hepatic foci were identified immunohistochemically and examined morphometrically. Although GST-P positive hepatic foci were detected in all groups including controls, the number and area of GST-P positive hepatic foci were significantly higher in female rats treated with 100 mg/kg than those in controls. In this paper, possible mechanisms of specific lesions in the liver and Harderian glands will be discussed.
- 日本トキシコロジー学会の論文
- 1999-08-17
著者
-
Sagami Fumio
第一三共安全性研究所
-
Sagami Fumio
Drug Safety Research Laboratories Eisai Co. Ltd.
-
Sagami Fumio
Subcommittee Of Non-clinical Evaluation Drug Evaluation Committee Japan Pharmaceutical Manufacturers
-
Sagami Fumio
Department Of Drug Safety Research Eisai Kawashima Research Laboratories Eisai Co. Ltd.
-
AOKI Toyohiko
Drug Safety Research Laboratories, Eisai Co., Ltd.
-
Aoki Toyohiko
Global Drug Safety Eisai Co. Ltd.
-
TSUKIDATE Kazuo
Drug Safety Research Laboratories, Eisai Co., Ltd
-
SATO Gen
Drug Safety Research Laboratories
-
Sato Gen
Drug Safety And Disposition
-
Sato Gen
Drug Safety Research Laboratories Eisai Co. Ltd.
-
HOSOKAWA Satoru
Drug Safety Research Lab., Eisai Co., Ltd.
-
Tsukidate Kazuo
Global Drug Safety Eisai Co. Ltd.
-
Tsukidate Kazuo
Drug Safety Research Lab. Eisai Co. Ltd.
-
CHIMOTO Tadashi
Drug Safety and Disposition
-
SUMIGAMA Shuji
Drug Safety & Disposition Research Laboratories, Eisai Co., Lid.
-
Sumigama Shuji
Drug Safety & Disposition Research Laboratories Eisai Co. Lid.
-
Hosokawa Satoru
Drug Safety And Disposition
-
Aoki Toyohiko
Drug Safety Japan Global Drug Safety Biopharmaceutical Assessments Core Function Unit
-
Sagami Fumio
Drug Safety Research Laboratories Eisai Co. Ltb.
-
Chimoto Tadash
Drug Safety & Disposition Research Laboratories, Eisai Co., Lid.
関連論文
- The predictivity of preliminary embryo-fetal development (EFD) studies : results of a retrospective survey in Japanese pharmaceutical companies
- Collaborative work on evaluation of ovarian toxicity by repeated-dose and fertility studies in female rats
- Current Status of Carcinogenicity Assessment of Peroxisome Proliferator-Activated Receptor Agonists by the US FDA and a Mode-of-Action Approach to the Carcinogenic Potential
- Proteomic analysis for neuronal vacuolation induced by MK-801 in rat retrosplenial cortex
- Safety assessment of biopharmaceuticals : Japanese perspective on ICH S6 guideline maintenance
- Points to consider on the non-clinical safety evaluation of anticancer drugs
- CURRENT OPINION : SAFETY EVALUATION OF DRUG METABOLITES IN DEVELOPMENT OF PHARMACEUTICALS
- "POINTS TO CONSIDER" REGARDING SAFETY ASSESSMENT OF BIOTECHNOLOGY-DERIVED PHARMACEUTICALS IN NON-CLINICAL STUDIES (ENGLISH TRANSLATION)
- Current status of pharmaceutical industries in Japan on pharmacogenomics and toxicogenomics in 2005(Toxicogenomics, Toxicoproteomics, Proceedings of the 32nd Annual Meeting)
- S3-6 Problems and Meanings of Genome-based Drug Discovery in Japanese Pharmaceutical Companies(SYMPOSIUM 3: BENEFITS OF PHARMACOGENOMICS/PHARMACOGENETICS IN PHARMACEUTICAL DEVELOPMENT)(Proceedings of the 31st Annual Meeting)
- A Comparision of the Results of Rat and Mouse Carcinogenicity Studies Conducted on Pharmaceuticals
- A new method for preparing electron microscopic specimens of Helicobacter pylon
- P-15 Investigational study for hepatotoxicity in rats by E2011 repeated administration. 2) Bioactivation of benzothiazoles with amine structures in the Ames mutagenicity assay.(Proceedings of the 27th Annual Meeting)
- P7-39 Current Analysis and Prospects of New Toxicological Biomarker : Biomarkers of Hepatotoxicity(GENERAL TOXICITY)(GENERAL SESSION BY POSTER PRESENTATION)(Proceedings of the 31st Annual Meeting)
- P7-38 Current analysis and prospects of new toxicological biomarker : biomarkers of cardiotoxicity(GENERAL TOXICITY)(GENERAL SESSION BY POSTER PRESENTATION)(Proceedings of the 31st Annual Meeting)
- P7-37 Current Analysis and Prospects of New Toxicological Biomarker : Biomarkers of Nephrotoxicity(GENERAL TOXICITY)(GENERAL SESSION BY POSTER PRESENTATION)(Proceedings of the 31st Annual Meeting)
- S13-1 Current analysis and prospects of new toxicological biomarkers : with central focus on heart, liver and kidney(SYMPOSIUM 13: CURRENT STATUS AND FUTURE ASPECTS OF NEW TOXICOLOGICALLY RESPONSIBLE BIOMARKERS)(Proceedings of the 31st Annual Meeting)
- STUDIES ON EXPERIMENTAL IODINE ALLERGY : 3. LOW MOLECULAR WEIGHT ELICITOGENIC ANTIGENS OF IODINE ALLERGY
- STUDIES ON EXPERIMENTAL IODINE ALLERGY : 2. IODINATED PROTEIN ANTIGENS AND THEIR GENERATION FROM INORGANIC AND ORGANIC IODINE-CONTAINING CHEMICALS
- STUDIES ON EXPERIMENTAL IODINE ALLERGY : 1. ANTIGEN RECOGNITION OF GUINEA PIG ANTI-IODINE ANTIBODY
- P6-44 The effects of chronic dietary restriction on biological characteristics in Crj:CD(SD)IGS rats(DRUG METABOLISM/CARCINOGENICITY)(GENERAL SESSION BY POSTER PRESENTATION)(Proceedings of the 31st Annual Meeting)
- Collaborative work on evaluation of ovarian toxicity : 11) Two- or four-week repeated-dose studies and fertility study of ethylene glycol monomethyl ether in female rats
- MECHANISM OF WEIGHT GAIN SUPPRESSING EFFECT OF ER-40133, AN ANGIOTENSIN I CONVERTING ENZYME INHIBITOR, IN GROWING RATS
- P-11 Application of hepatocytes cultured in a sandwich configuration to toxicity assessment.(Proceedings of the 27th Annual Meeting)
- P8-43 Study on the difference of CK activity between plasma and serum in monkey(BLOOD/TOXICOKINETICS/OTHERS-2)(GENERAL SESSION BY POSTER PRESENTATION)(Proceedings of the 31st Annual Meeting)
- Paracortical hyperplasia of superficial lymph nodes in a new mutant strain of hairless rats (ISh) : A lesion similar to human dermatopathic lymphadenopathy
- Mechanism for benzothiazole derivative-induced hepatotoxicity in rats(SYMPOSIUM 1 : MECHANISMS OF HEPATOTOXIC EFFECTS)
- P-90 Collaborative Work to Evaluate Toxicity on Male Reproductive Organs with 2 Weeks Repeated Daily Dosing in Rats : Testicular Toxicity of E7010, A Sulfonamide Tubulin Polymerlzation Inhibitor(Proceedings of the 27th Annual Meeting)
- COLLABORATIVE WORK TO EVALUATE TOXICITY ON MALE REPRODUCTIVE ORGANS BY REPEATED DOSE STUDIES IN RATS : 17)TESTICULAR TOXICITY OF E7010, A SULFONAMIDE TUBULIN POLYMERIZATION INHIBITOR
- TOXICOLOGICAL RESPONSE OF RATS TO A NOVEL MONOAMINE OXIDASE TYPE-A INHIBITOR, (5R)-3-[2-((1S)-3-CYANO-1-HYDROX-YPROPYL)BENZOTHIAZOL-6-YL]-5-METHOXYMETHYL-2-OXAZOLIDI-NONE (E2011), ORALLY ADMINISTERED FOR 13 WEEKS
- "B-5 Modification of Drug Conjugation Pathway by Repeated Administration of Conjugating Enzyme Inhibitors in Rats.
- 21C-02-4 Hepatic Drug Metabolizing Enzymes in CB6F1-TgrasH2 Mice.
- Inhibitory Effect of Dimethyl Sulfoxide on the Mutagenicity of Promutagens in the Ames Test
- Cytotoxic Effect of Dimethyl Sulfoxide in the Ames Test
- TOXICOKINETICS:ITS SIGNIFICANCE AND PRACTICAL PROBLEMS
- Report 4 : CASE STUDY OF CARCINOGENICITY BY INITIATION-PROMOTION MODEL (CARCINOGENlClTY STUDIES)
- Proteomic analysis for neuronal vacuolation induced by MK-801 in rat retrosplenial cortex
- DETERMINATION OF THE TIME AT WHICH CONGENITAL HYDROCEPHALUS IS INDUCED WITH HIGHER INCIDENCE DURING THE EARLY GESTATIONAL PERIOD IN RATS
- "A-4 Mechanisms of cytotoxicity of cultured rat hepatocytes by naphthoquinones.
- ^1H-NMR Based Metabonomics Study of Galactosamine, Methylene Dianiline, and Clofibrate in Rats(Liver, Alimentary system, Proceedings of the 32nd Annual Meeting)
- P6-57 NMR spectroscopic analysis of rat urine samples after D-galactosamine or 4-aminophenol administration(TOXICOGENOMICS)(GENERAL SESSION BY POSTER PRESENTATION)(Proceedings of the 31st Annual Meeting)
- MANUAL METHOD FOR QUALITATIVE AND QUANTITATIVE ASSESSMENT OF MALE REPRODUCTIVE EFFECTS IN RATS