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Cardiovascular Toxicology

, Volume 18, Issue 1, pp 76–83 | Cite as

The Cardiovascular Effect of Single Injection and Toxicologic Effects of Repetitive 2-Week Intravenous Administration of Activin A/BMP-2 Chimera in Beagle Dog

  • Jae Hyup LeeEmail author
  • Senyon Choe
  • Shihuan Han
Article

Abstract

This study was performed for the purpose to evaluate the effect of activin A/BMP-2 chimera (AB204) on cardiovascular system and toxicological effect in beagle dogs. When administered AB204 at the dose of 0.32 mg/kg via intravenous injection in beagle dogs, there were no changes in systolic, diastolic and mean blood pressure as well as in pulse rate, in addition that there were no differences in ORS complex, PR interval, R–R interval, QT interval and QTcV interval on the electrocardiography. Also, when administered AB204 at the doses of 0.25 and 0.5 mg/kg/day via repetitive intravenous injection for 2 weeks, it did not cause any significant changes in general symptoms, weight, food intake, ophthalmologic abnormality, urine, hematology, serum biochemistry, organ weight and autopsy values. Therefore, AB204 did not affect cardiovascular functions including blood pressure, pulse rate and ECG, when administered at the dose of ≤0.32 mg/kg via single intravenous injection in male beagle dogs. When it was administered at the dose of 0.5 mg/kg repetitive intravenous injection for 2 weeks, it did not show any toxicity.

Keywords

Activin A rhBMP-2 Intravenous administration Cardiovascular function Toxicity In vivo 

Notes

Acknowledgements

This work was supported by Mid-career Researcher Program through NRF Grant (2016R1A2B3015048) funded by the Korea government (MSIP).

Compliance with Ethical Standards

Conflict of interest

All authors disclose here that there are no conflicts of interest that could inappropriately have influenced the outcome of the present study.

Supplementary material

12012_2017_9415_MOESM1_ESM.doc (97 kb)
Supplementary material 1 (DOC 97 kb)

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Department of Orthopedic SurgerySeoul National University, College of MedicineSeoulKorea
  2. 2.Medical Research Center, Institute of Medical and Biological EngineeringSeoul National UniversitySeoulKorea
  3. 3.Protein Engineering LaboratoryJoint Center for Biosciences at Songdo Smart ValleyIncheonKorea
  4. 4.School of Biology, Qualcomm InstituteUniversity of California San DiegoLa JollaUSA
  5. 5.Department of Orthopedic SurgeryYanBian University HospitalYanjiChina
  6. 6.Department of Orthopedic SurgerySMG-SNU Boramae Medical CenterSeoulKorea

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