Campus Units
Biomedical Sciences, Veterinary Clinical Sciences, Veterinary Diagnostic and Production Animal Medicine
Document Type
Article
Publication Version
Published Version
Publication Date
11-7-2019
Journal or Book Title
Frontiers in Veterinary Science
Volume
6
First Page
385
DOI
10.3389/fvets.2019.00385
Abstract
Background: High-dose, pharmacological ascorbate (P-AscH−) is preferentially cytotoxic to human cancer cells in vitro. Investigations on the efficacy of P-AscH− as an adjuvant treatment for multiple human cancers are on-going, but has yet to be formally investigated in dogs. The primary objectives of this study were to determine the pharmacokinetic (PK) profile of P-AscH− in healthy Beagle dogs and the effects of P-AscH− on canine osteosarcoma cells in vitro.
Methods: Eight purpose-bred, healthy, spayed female Beagle dogs, between 20 and 21 months old, and 8–10 kg were administered two doses of P-AscH− (550 or 2,200 mg/kg) via intravenous infusion over 6 h, on separate days. Plasma ascorbate concentrations were measured at 12 time points during and after infusion for PK analysis using nonlinear mixed-effects (NLME) and non-compartmental analysis (NCA). Clonogenic assays were performed on 2 canine osteosarcoma cell lines (D-17 and OSCA-8) and canine primary dermal fibroblasts after exposure to high concentrations of ascorbate (75 pmoles/cell).
Results: Plasma ascorbate levels in the dogs peaked at approximately 10 mM following 2,200 mg/kg and returned to baseline 6–8 h after dosing. Minor adverse effects were seen in two dogs. Ascorbate (75 pmoles/cell) significantly decreased survival in both the osteosarcoma cell lines (D-17 63% SD 0.010, P = 0.005; OSCA-8 50% SD 0.086, P = 0.026), compared to normal fibroblasts (27% SD 0.056).
Conclusions: Pharmacological ascorbate is preferentially cytotoxic to canine-derived cancer cells. High levels of ascorbate can be safely administered to dogs. Further studies are needed to determine the effects of P-AscH− on canine patients.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Copyright Owner
Musser, Mahaffey, Fath, Buettner, Wagner, Schneider, Seo, Mochel and Johannes
Copyright Date
2019
Language
en
File Format
application/pdf
Recommended Citation
Musser, Margaret L.; Mahaffey, Alyssa L.; Fath, Melissa A.; Buettner, Garry R.; Wagner, Brett A.; Schneider, Benjamin K.; Seo, Yeon-Jung; Mochel, Jonathan P.; and Johannes, Chad M., "In vitro Cytotoxicity and Pharmacokinetic Evaluation of Pharmacological Ascorbate in Dogs" (2019). Biomedical Sciences Publications. 74.
https://lib.dr.iastate.edu/bms_pubs/74
Included in
Small or Companion Animal Medicine Commons, Veterinary Toxicology and Pharmacology Commons
Comments
This article is published as Musser, Margaret, Alyssa L. Mahaffey, Melissa Ann Fath, Garry R. Buettner, Brett A. Wagner, Benjamin K. Schneider, Yeon-Jung Seo, Jonathan Paul Mochel, and Chad M. Johannes. "In vitro Cytotoxicity and Pharmacokinetic Evaluation of Pharmacological Ascorbate in Dogs." Frontiers in Veterinary Science 6 (2019): 385. DOI: 10.3389/fvets.2019.00385. Posted with permission.