Frontiers in Pharmacology (Oct 2019)

Toxicity Study of 28-Day Subcutaneous Injection of Arctigenin in Beagle Dogs

  • Jie Li,
  • Jie Li,
  • Jie Li,
  • Yun-gang Lv,
  • Li-hong Pan,
  • Li-hong Pan,
  • Li-hong Pan,
  • Fang-fang Yao,
  • Fang-fang Yao,
  • Tao Peng,
  • Tao Peng,
  • Tao Peng,
  • Yu-jun Tan,
  • Yu-jun Tan,
  • Yu-jun Tan,
  • Gui-Min Zhang,
  • Gui-Min Zhang,
  • Gui-Min Zhang,
  • Gui-Min Zhang,
  • Zhong Liu,
  • Zhong Liu,
  • Zhong Liu,
  • Zhong Liu,
  • Jing-chun Yao,
  • Jing-chun Yao,
  • Jing-chun Yao,
  • Yu-shan Ren,
  • Yu-shan Ren,
  • Yu-shan Ren

DOI
https://doi.org/10.3389/fphar.2019.01218
Journal volume & issue
Vol. 10

Abstract

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Our previous studies have investigated the systematic pharmacokinetic characteristics, biological activities, and toxicity of arctigenin. In this research, the potential toxicities of arctigenin in beagle dogs were investigated via repeated 28-day subcutaneous injections. Beagle dogs were randomly divided into control, vehicle [polyethylene glycol (PEG)], and arctigenin 6, 20, 60 mg/kg treated groups. The whole experimental period lasted 77 days, including adaptive period (35 days), drug exposure period (animals were treated with saline, PEG, or arctigenin for 28 consecutive days), and recovery period (14 days). Arctigenin injection (60 mg/kg) affected the lymphatic hematopoietic, digestive, urinary, and cardiovascular systems, and all the impact on these tissues resulted in death in five dogs (three female and two male dogs); 20 mg/kg arctigenin injection resulted in toxic reactions of the lymphatic hematopoietic and digestive systems; and 6 mg/kg arctigenin and PEG injection did not lead to significant toxic reactions. Meanwhile, there were no sexual differences of drug exposure and accumulation when dogs underwent different dosages. As stated previously, the toxic target organs of arctigenin administration include lymphatic hematopoietic, digestive (liver and gallbladder), urinary (kidney), and cardiovascular (heart) systems, and the no observed adverse effect level (NOAEL) of arctigenin is less than 6 mg/kg.

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