A Pilot Study on the Safety of a Novel Antioxidant Nanoparticle Delivery System and Its Indirect Effects on Cytokine Levels in Four Dogs.
antioxidant
canine
catalase
nanoparticle
spinal cord injury
superoxide dismutase
Journal
Frontiers in veterinary science
ISSN: 2297-1769
Titre abrégé: Front Vet Sci
Pays: Switzerland
ID NLM: 101666658
Informations de publication
Date de publication:
2020
2020
Historique:
received:
21
04
2020
accepted:
19
06
2020
entrez:
28
8
2020
pubmed:
28
8
2020
medline:
28
8
2020
Statut:
epublish
Résumé
Acute spinal cord injury consists of a primary, traumatic event followed by a cascade of secondary events resulting in ongoing cell damage and death. There is great interest in prevention of these secondary effects to reduce permanent long-term neurologic deficits. One such target includes reactive oxygen species released following injury, which can be enzymatically converted into less harmful molecules by superoxide dismutase and catalase. Canine intervertebral disc herniation has been suggested as a naturally occurring model for acute spinal cord injury and its secondary effects in people. The aims of this study were to test the safety of a novel antioxidant delivery system in four healthy dogs and to indirectly test effect of delivery via cytokine measurement. All dogs experienced adverse events to some degree, with two experiencing adverse events considered to be severe. The clinical signs, including combinations of bradycardia, hypotension, hypersalivation, pale gums, and involuntary urination, were consistent with complement activation-related pseudoallergy (CARPA). CARPA is a well-known phenomenon that has been reported to occur with nanoparticle-based drug delivery, among other documented causes. Two dogs also had mild to moderate changes in their blood cell count and chemistry, including elevated alanine transferase, and thrombocytopenia, which both returned to normal by day 7 post-administration. Cytokine levels trended downwards over the first 3 days, but many were elevated at measurement on day 7. Intradermal testing suggested catalase as a potential cause for reactions. No long-term clinical signs were observed, and necropsy results revealed no concerning pathology. Additional evaluation of this product, including further characterization of reactions to catalase containing components, dose-escalation, and desensitization should be performed before evaluation in clinically affected dogs.
Identifiants
pubmed: 32851027
doi: 10.3389/fvets.2020.00447
pmc: PMC7406565
doi:
Types de publication
Journal Article
Langues
eng
Pagination
447Informations de copyright
Copyright © 2020 Robinson, Platt, Bibi, Banovic, Barber, Howerth and Madsen.
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