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Veterinary research communications1997; 21(5); 361-368; doi: 10.1023/a:1005816422279

The effect of the acute-phase response on in vitro drug metabolism and plasma protein binding in the horse.

Abstract: The effect of the acute-phase response (APR) on the activity of the hepatic drug-metabolizing system (DMS) and on the binding of phenylbutazone to plasma proteins was investigated in the horse. An APR was induced by intramuscular injections of Freund's complete adjuvant in five horses and, five days later, these horses together with five clinically normal horses were shot and the right ventral lobe of each liver removed. The hepatic microsomal fractions from the liver samples were isolated and significantly lower (p < 0.01) concentrations of cytochromes P450 and b5 and activities of aniline-p-hydroxylase and aminopyrine N-demethylase (43%, 55%, 45% and 30%, respectively) were measured in the livers from the adjuvant-inflamed horses, compared to the controls. Phenylbutazone (PBZ) was administered intravenously (4.4 mg/kg) to a further four horses and plasma protein binding was measured by ultracentrifugation. Five weeks later, these horses were injected with Freund's complete adjuvant and the intravenous administration of PBZ (4.4 mg/kg) was repeated. Inflammation induced a significant increase (p < 0.01) in the unbound fraction of PBZ (5.2 +/- 0.5 as against 1.4 +/- 0.6%). These results suggest that the APR depresses the hepatic DMS and reduces the binding of PBZ to plasma proteins.
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Publication Date: 1997-07-01 PubMed ID: 9232780DOI: 10.1023/a:1005816422279Google Scholar: Lookup
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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 study examined the impact of an acute inflammation response in horses on the functionality of the liver’s drug metabolism system and how it alters the binding of a specific drug (phenylbutazone) to plasma proteins. The investigations showed that inflammation caused a significant decrease in the metabolic activities of the liver and reduced the binding of phenylbutazone to plasma proteins.

Research Methodology

  • The acute-phase response (APR), a typical response to inflammation, was artificially stimulated in five horses using intramuscular injections of Freund’s complete adjuvant – a substance that boosts immune response.
  • Five days later, these horses, along with five clinically normal horses (acting as control), were euthanized and a part of the liver (the right ventral lobe) of each horse was removed for analysis.
  • The hepatic microsomal fractions, cellular components where drug metabolism happens, from the liver samples were isolated.

Investigation on Hepatic Drug-Metabolizing System (DMS)

  • The liver samples’ concentrations of cytochromes P450 and b5, and activities of aniline-p-hydroxylase and aminopyrine N-demethylase, were measured. These are all crucial components in drug metabolism.
  • The measurements showed significantly lower concentrations and activities in the livers from the horses with induced inflammation, compared to the control horses.

Study on Plasma Protein Binding

  • Phenylbutazone (PBZ), a non-steroidal anti-inflammatory drug commonly used in equine practice, was administered intravenously to four additional horses.
  • The binding of this drug to plasma proteins was measured via a method called ultracentrifugation. This process involves extreme centrifuging designed to separate tiny particles like proteins.
  • After five weeks, the horses were injected with Freund’s complete adjuvant (just like the previous set of horses) to induce an acute inflammation response.
  • The intravenous administration of PBZ was repeated and plasma protein binding measured once again.
  • The study found a significant increase in the unbound fraction of PBZ in the horses after inflammation was induced.

Findings and Conclusion

  • All the results indicate that the APR indeed decreases the function of the liver’s drug metabolism system and reduces the binding of PBZ to plasma proteins.
  • This implies that during acute inflammation, the metabolism and effect of drugs may be significantly altered in horses. This is an essential insight for equine health and veterinary medicine.

Cite This Article

APA
Mills PC, Ng JC, Auer DE. (1997). The effect of the acute-phase response on in vitro drug metabolism and plasma protein binding in the horse. Vet Res Commun, 21(5), 361-368. https://doi.org/10.1023/a:1005816422279

Publication

Veterinary research communications
ISSN: 0165-7380
NlmUniqueID: 8100520
Country: Switzerland
Language: English
Volume: 21
Issue: 5
Pages: 361-368

Researcher Affiliations

Mills, P C
  • Department of Veterinary Pathology, University of Queensland, St Lucia, Australia.
Ng, J C
    Auer, D E

      MeSH Terms

      • Acute-Phase Reaction / metabolism
      • Acute-Phase Reaction / veterinary
      • Aminopyrine N-Demethylase / metabolism
      • Aniline Hydroxylase / metabolism
      • Animals
      • Blood Proteins / metabolism
      • Cytochrome P-450 Enzyme System / metabolism
      • Freund's Adjuvant / pharmacology
      • Horses / metabolism
      • In Vitro Techniques
      • Infusions, Intravenous
      • Microsomes, Liver / enzymology
      • Phenylbutazone / metabolism
      • Phenylbutazone / pharmacology

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      Citations

      This article has been cited 1 times.
      1. Khalil RH, Al-Humadi N. Types of acute phase reactants and their importance in vaccination. Biomed Rep 2020 Apr;12(4):143-152.
        doi: 10.3892/br.2020.1276pubmed: 32190302google scholar: lookup
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