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Peer-reviewed veterinary case report

Valproic acid reduces inflammation in dogs with endotoxemia

By Song, Ruhui et al.·Published in Veterinary immunology and immunopathology·2015·Department of Veterinary Internal Medicine, South Korea·View original on PubMed

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Original publication title: Valproic acid attenuates the expression of pro-inflammatory cytokines lipopolysaccharide-treated canine peripheral blood mononuclear cells (in vitro) and in a canine endotoxemia model (in vivo).

Species:
dog

Plain-English summary

A group of Beagle dogs with endotoxemia, a serious condition caused by bacterial toxins, were treated with valproic acid (VPA) to see if it could help reduce inflammation. The dogs showed high levels of inflammatory markers, but after receiving VPA, these levels significantly decreased within a few hours. This suggests that VPA may be effective in lowering inflammation in dogs suffering from sepsis, which is a severe response to infection. The results indicate that VPA could be a helpful treatment option for managing inflammation in affected dogs.

People also search for: dog sepsis treatment · Beagle inflammation medication · valproic acid for dogs

Abstract

Valproic acid (VPA), a known histone deacetylase inhibitor, has been used as an anticonvulsant in dogs. VPA also has anti-inflammatory properties, but there are no reports on the immunomodulatory effects of VPA in canine endotoxemia. In the present study, we demonstrate that the use of VPA significantly reduces the production of early-phase pro-inflammatory cytokines (TNF-&#x3b1;, IL-6) caused by lipopolysaccharide (LPS) stimulation both in vitro and in vivo. For the in vitro study, VPA was evaluated for 24h on LPS (100 ng/ml)-treated canine peripheral blood mononuclear cells (PBMCs) which isolated from 5 healthy Beagle dogs. VPA significantly decreased the mRNA expression of TNF-&#x3b1; and IL-6 in a dose-dependent manner (p<0.05 for IL-6; p<0.01 for TNF-&#x3b1;). Fourteen adult Beagles were studied for in vivo study; nine dogs received a low dose of LPS (10 &#x3bc;g/kg/h) via continuous IV infusion for 12h to induce endotoxemia whereas 5 dogs received normal saline as controls. Four out of 9 endotoxemic dogs were administered VPA (50mg/kg, IV) at 1h and 12h along with the LPS infusion. Three hours after the first administration of VPA, IL-6 mRNA expressions in PBMCs significantly decreased (p=0.033 vs. LPS group). VPA also significantly decreased the circulating TNF-&#x3b1; (p=0.044 vs. LPS group at 3h) and IL-6 protein at 3h (p=0.034 vs. LPS group) and 6h (p=0.026 vs. LPS group) post-treatment. Our study suggests that VPA attenuates the expression of pro-inflammatory cytokines in a canine endotoxemia model in vitro and in vivo. We speculate that valproic acid may be useful for reducing inflammatory cytokine levels in dogs with sepsis.

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Original publication on PubMed: https://pubmed.ncbi.nlm.nih.gov/26160312/