Pentoxifylline inhibits mediator synthesis in an equine in vitro whole blood model of endotoxemia.
Abstract: Whole blood from 10 healthy horses was aseptically collected into heparin or citrate anticoagulant and incubated in vitro for 6 hr in the absence (saline control) or presence of 1 ng endotoxin/ml blood. Pentoxifylline (0.1, 1, 10, or 100 micrograms/ml blood) was added 1 hr before, at the same time, or 1 hr after endotoxin. As compared to saline controls, pentoxifylline alone had no effect on mediator production, with the exception of significantly increasing 6-ketoprostaglandin F1 alpha concentration. Pentoxifylline inhibited endotoxin-induced increases in tumor necrosis factor (TNF) and interleukin-6 (IL-6) activity in a dose-related fashion, whether added before, at the same time, or after endotoxin. Pentoxifylline significantly inhibited tissue factor activity, but only when added before endotoxin. Pentoxifylline had no effect on endotoxin-induced 6-keto-prostaglandin F1 alpha production, but significantly inhibited thromboxane B2 (TxB2) production. The results of this study indicate that pentoxifylline, at blood concentrations consistent with those achieved in vivo, has effects that may be beneficial in the treatment of endotoxemia.
Publication Date: 1994-12-01 PubMed ID: 7628064
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research article explores how Pentoxifylline, a drug, can inhibit the synthesis of inflammatory mediators in a lab-based blood model from horses experiencing endotoxemia. The study indicates that Pentoxifylline has the potential to be beneficial in the treatment of endotoxemia.
Research Methodology
- The researchers collected whole blood from 10 healthy horses in a sterile manner. The blood was put in either heparin or citrate anticoagulant.
- This blood was then incubated in vitro (in a controlled lab setting) for 6 hours, without any substances (saline control) or with 1 ng of endotoxin per ml of blood.
- Pentoxifylline was added to the blood either 1 hour before, simultaneously with, or 1 hour after the addition of endotoxin. The doses of Pentoxifylline varied: 0.1, 1, 10, or 100 micrograms per ml of blood.
Findings from the Study
- The study found that compared to the saline controls, Pentoxifylline had no impact on mediator production except for significantly increasing the concentration of 6-ketoprostaglandin F1 alpha.
- Pentoxifylline was able to inhibit the endotoxin-induced increases in tumor necrosis factor (TNF) and interleukin-6 (IL-6) activity, regardless of whether it was added before, with or after the endotoxin.
- Moreover, Pentoxifylline significanty inhibited tissue factor activity, but this effect was only observed when the drug was added before the endotoxin.
- Pentoxifylline, however, didn’t affect the production of 6-keto-prostaglandin F1 alpha induced by endotoxin. The drug was able to significantly inhibit the production of thromboxane B2 (TxB2).
Conclusions Drawn from the Research
- The collected data from this research suggest that Pentoxifylline inhibits the production of certain inflammatory mediators in a dose-related fashion in a lab-based blood model of infected horses.
- This action of Pentoxifylline is consistent with achievable concentrations in real-world, or in vivo, scenarios suggesting that the drug may offer beneficial effects in treating endotoxemia, a severe inflammatory condition.
Cite This Article
APA
Barton MH, Moore JN.
(1994).
Pentoxifylline inhibits mediator synthesis in an equine in vitro whole blood model of endotoxemia.
Circ Shock, 44(4), 216-220.
Publication
Researcher Affiliations
- Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens 30602, USA.
MeSH Terms
- 6-Ketoprostaglandin F1 alpha / biosynthesis
- Animals
- Endotoxins / administration & dosage
- Endotoxins / blood
- Endotoxins / pharmacology
- Horses / blood
- Interleukin-6 / biosynthesis
- Models, Biological
- Pentoxifylline / administration & dosage
- Pentoxifylline / pharmacology
- Thromboplastin / biosynthesis
- Thromboxane B2 / biosynthesis
- Tumor Necrosis Factor-alpha / biosynthesis
Citations
This article has been cited 3 times.- Uney K, Tras B, Corum O, Yildiz R, Maden M. Pharmacokinetics of pentoxifylline and its 5-hydroxyhexyl metabolite following intravenous administration in cattle. Trop Anim Health Prod 2019 Feb;51(2):435-441.
- Martin EM, Messenger KM, Sheats MK, Jones SL. Misoprostol Inhibits Lipopolysaccharide-Induced Pro-inflammatory Cytokine Production by Equine Leukocytes. Front Vet Sci 2017;4:160.
- Gomez DE, Kopper JJ, Byrne DP, Renaud DL, Schoster A, Dunkel B, Arroyo LG, Mykkanen A, Gilsenan WF, Pihl TH, Lopez-Navarro G, Tennent-Brown BS, Hostnik LD, Mora-Pereira M, Marques F, Gold JR, DeNotta SL, Desjardins I, Stewart AJ, Kuroda T, Schaefer E, Oliver-Espinosa OJ, Agne GF, Uberti B, Veiras P, Delph Miller KM, Gialleti R, John E, Toribio RE. Treatment approaches to horses with acute diarrhea admitted to referral institutions: A multicenter retrospective study. PLoS One 2024;19(11):e0313783.
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