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.

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.

Creative Commons License

Creative Commons Attribution 4.0 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

Language

en

File Format

application/pdf

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