Journal article
In vitro Cytotoxicity and Pharmacokinetic Evaluation of Pharmacological Ascorbate in Dogs
Frontiers in veterinary science, Vol.6, pp.385-385
11/07/2019
DOI: 10.3389/fvets.2019.00385
PMCID: PMC6854015
PMID: 31788483
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 (NAME) 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 prnoles/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.
Details
- Title: Subtitle
- In vitro Cytotoxicity and Pharmacokinetic Evaluation of Pharmacological Ascorbate in Dogs
- Creators
- Margaret L. Musser - Iowa State UniversityAlyssa L. Mahaffey - Iowa State UniversityMelissa A. Fath - University of IowaGarry R. Buettner - University of IowaBrett A. Wagner - University of IowaBenjamin K. Schneider - Iowa State UniversityYeon-Jung Seo - Iowa State UniversityJonathan P. Mochel - Iowa State UniversityChad M. Johannes - Iowa State University
- Resource Type
- Journal article
- Publication Details
- Frontiers in veterinary science, Vol.6, pp.385-385
- DOI
- 10.3389/fvets.2019.00385
- PMID
- 31788483
- PMCID
- PMC6854015
- NLM abbreviation
- Front Vet Sci
- ISSN
- 2297-1769
- eISSN
- 2297-1769
- Publisher
- Frontiers Media Sa
- Number of pages
- 11
- Grant note
- University of Iowa Sarcoma Group R01 CA169046; P01CA217797 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 11/07/2019
- Academic Unit
- Radiation Oncology
- Record Identifier
- 9984312979702771
Metrics
6 Record Views