Cardiotoxic Changes of Colchicine Intoxication in Rats: Electrocardiographic, Histopathological and Blood Chemical Analysis

• Tochinai Ryota

  Safety Research Department, Yakult Central Institute

• Suzuki Katsuya

  Safety Research Department, Yakult Central Institute

• Nagata Yuriko

  Safety Research Department, Yakult Central Institute

• Ando Minoru

  Safety Research Department, Yakult Central Institute

• Hata Chie

  Safety Research Department, Yakult Central Institute

• Komatsu Kayoko

  Safety Research Department, Yakult Central Institute

• Suzuki Tomo

  Safety Research Department, Yakult Central Institute

• Uchida Kazumi

  Safety Research Department, Yakult Central Institute

• Kado Shoichi

  Safety Research Department, Yakult Central Institute

• Kaneko Kimiyuki

  Safety Research Department, Yakult Central Institute

• Kuwahara Masayoshi

  Department of Veterinary Pathophysiology and Animal Health, Graduate School of Agricultural and Life Sciences

抄録

The microtubule inhibitor colchicine is cardiotoxic and is suggested to impair impulse formation and conduction. However, little is known about the electrocardiographic (ECG) changes induced by colchicine in experimental animals and the detailed pathogenesis of its cardiotoxicity. Therefore, we analyzed cardiotoxicity in colchicine-treated rats using electrocardiographic, histopathological and blood-chemistry approaches. A telemetry device for transmitting ECG data was implanted into male Crl:CD(SD) rats, and ECG tracings were obtained. At 6 weeks of age, 1.25 mg/kg colchicine was injected intravenously once daily for 2 consecutive days, and ECG waveforms and heart rate variability were analyzed. Furthermore, 1.25 mg/kg colchicine or vehicle was injected for 1 or 2 consecutive days in other rats at 6 weeks of age. One day after the final dosing, heart and blood samples were taken for histopathological and bloodchemical examination. ECG analysis revealed a prolonged RR interval, QRS duration, PR interval and QT interval. Heart rate variability analysis showed an increase in high frequency (HF) components as an index of parasympathetic nervous activity. In blood chemical examinations, colchicine induced high levels of parameters of cardiac injury and low levels and/or variations in Ca, inorganic phosphorus, potassium and chloride. Histopathologically, colchicine-treated rats showed eosinophilic granular degeneration and cytoplasmic vacuolation of ventricular myocardial cells but no remarkable change in the atrioventricular node. Not only blood chemical and histopathological changes but also ECG changes were induced in colchicine-treated rats, which indicated a decrease in myocardium excitability and conductivity, and these changes might be related to increased parasympathetic nervous activity and low blood Ca levels.

収録刊行物

• Ｊｏｕｒｎａｌ　ｏｆ　Ｔｏｘｉｃｏｌｏｇｉｃ　Ｐａｔｈｏｌｏｇｙ

  Ｊｏｕｒｎａｌ　ｏｆ　Ｔｏｘｉｃｏｌｏｇｉｃ　Ｐａｔｈｏｌｏｇｙ 27 (3+4), 223-230, 2014

  日本毒性病理学会

キーワード

• colchicine
• cardiotoxicity
• electrocardiogram
• heart rate variability
• parasympathetic nerve
• rat

詳細情報

• CRID: 1390282679392885888
• NII論文ID: 130004433135
• NII書誌ID: AN10232280
• DOI: 10.1293/tox.2014-0013
• ISSN: 1881915X
• ISSN: 09149198
• NDL書誌ID: 025899938
• PubMed: 25378807
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I025899938
• Web Site: https://www.jstage.jst.go.jp/article/tox/27/3+4/27_2014-0013/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2015248511
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可