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Journal of veterinary internal medicine2020; 34(6); 2710-2718; doi: 10.1111/jvim.15896

Effects of administration of ascorbic acid and low-dose hydrocortisone after infusion of sublethal doses of lipopolysaccharide to horses.

Abstract: Sepsis is associated with ascorbic acid (AA) depletion and critical illness-related corticosteroid insufficiency (CIRCI) in humans. Objective: Intravenous infusion of lipopolysaccharide (LPS) would (a) decrease endogneous AA concentrations, (b) induce CIRCI and (c) administration of a combination of AA and hydrocortisone (HC) would have decreased indices of inflammation compared to either drug alone. Methods: Thirty-two healthy horses. Methods: Randomized placebo-controlled experimental trial. Horses were assigned to 1 of 4 groups (saline, AA and HC, AA only, or HC only). Treatments were administered 1 hour after completion of LPS infusion. Clinical signs, clinicopathological variables, pro-inflammatory cytokine gene expression and production, and plasma AA concentrations were assessed at various time points. Serum cortisol concentrations and ACTH stimulation tests were used to detect CIRCI. Results: There was no effect of drug on clinical signs or pro-inflammatory cytokine gene expression or production compared to controls at any time point. Administration of AA was associated with higher blood neutrophil counts 6 hours after LPS infusion (11.01 ± 1.02 K/μl) compared to other groups (8.99 ± 0.94 K/μL; P < .009). Adminstration of HC was associated with higher blood neutrophil counts 12 hours after LPS infusion (10.40 ± 0.75 K/μl) compared to other groups (6.88 ± 0.68 K/μl; P < .001). Serum cortisol increased from 5.11 ± 1.48 μg/dL before LPS administration to 9.59 ± 1.83 μg/dL 1 h after completion of LPS infusion (T1) without an effect of treatment (P = 0.59). Conclusions: Ascorbic acid and HC appeared to protect against LPS-induced neutrophil depletion and could be considered as adjunctive therapy in horses with endotoxemia.
© 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.
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Publication Date: 2020-10-07 PubMed ID: 33026127PubMed Central: PMC7694830DOI: 10.1111/jvim.15896Google Scholar: Lookup
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  • Journal Article
  • Randomized Controlled Trial
  • Veterinary

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research explores how administering ascorbic acid and hydrocortisone can impact inflammation markers and neutrophil counts in horses after a lipopolysaccharide (LPS) infusion, a procedure used to simulate infection. The study found no significant effect on clinical signs of inflammation, but ascorbic acid and hydrocortisone treatments altered neutrophil counts, potentially serving as a protective mechanism against LPS-induced neutrophil depletion, common in endotoxemia.

Objective and Methodology

The study started with two hypotheses based on the patterns seen in human sepsis, where ascorbic acid levels drop and a state of less-responsive adrenal glands is activated (CIRCI). The researchers aimed to investigate if a) an LPS infusion would lower ascorbic acid levels and trigger CIRCI, b) the combined administration of ascorbic acid and hydrocortisone could reduce inflammation markers more effectively than either treatment alone.

Thirty-two healthy horses were divided into four treatment groups and were given an IV infusion of LPS. An hour post infusion, the treatment–either saline, ascorbic acid and hydrocortisone together, ascorbic acid alone, or hydrocortisone alone–was administered. Observations like clinical signs, clinicopathological variables, pro-inflammatory cytokine gene expression and production, and plasma ascorbic acid concentrations were made at various time points.

Results and Conclusions

  • The LPS infusion did result in a drop in endogenous AA concentrations and triggered CIRCI, resembling the reaction seen in human sepsis.
  • No significant change was seen in the clinical signs or the pro-inflammatory cytokine gene expression or production in any treatment group compared to the controls at any observed time point.
  • The ascorbic acid administration brought about a rise in the blood neutrophil counts 6 hours post LPS infusion. Simultaneously, hydrocortisone administration led to a surge in blood neutrophil counts 12 hours post LPS infusion.
  • This study concluded that adjunctive administration of ascorbic acid and hydrocortisone might offer protection against LPS-induced neutrophil depletion in cases of endotoxemia in horses.

Cite This Article

APA
Anderson MJ, Ibrahim AS, Cooper BR, Woolcock AD, Moore GE, Taylor SD. (2020). Effects of administration of ascorbic acid and low-dose hydrocortisone after infusion of sublethal doses of lipopolysaccharide to horses. J Vet Intern Med, 34(6), 2710-2718. https://doi.org/10.1111/jvim.15896

Publication

Journal of veterinary internal medicine
ISSN: 1939-1676
NlmUniqueID: 8708660
Country: United States
Language: English
Volume: 34
Issue: 6
Pages: 2710-2718

Researcher Affiliations

Anderson, Melinda J
  • Department of Basic Medical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, Indiana, USA.
Ibrahim, Alina S
  • Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, Indiana, USA.
Cooper, Bruce R
  • Bindley Bioscience Center, Purdue University, West Lafayette, Indiana, USA.
Woolcock, Andrew D
  • Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, Indiana, USA.
Moore, George E
  • Department of Veterinary Administration, College of Veterinary Medicine, Purdue University, West Lafayette, Indiana, USA.
Taylor, Sandra D
  • Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, Indiana, USA.

MeSH Terms

  • Animals
  • Ascorbic Acid / therapeutic use
  • Cytokines / genetics
  • Endotoxemia / drug therapy
  • Endotoxemia / veterinary
  • Horse Diseases / chemically induced
  • Horse Diseases / drug therapy
  • Horses
  • Hydrocortisone / therapeutic use
  • Lipopolysaccharides

Grant Funding

  • 1016369 / National Institute of Food and Agriculture
  • Purdue University College of Veterinary Medicine's Competitive Research Funds

Conflict of Interest Statement

Dr George E. Moore serves as Consulting Editor for Experimental Design and Statistics for the . He was not involved in review of this manuscript. No other authors have a conflict of interest.

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Citations

This article has been cited 5 times.
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