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American journal of veterinary research2000; 61(2); 152-157; doi: 10.2460/ajvr.2000.61.152

Hepatic and pulmonary enzyme activities in horses.

Abstract: To determine hepatic and pulmonary phase-I and phase-II enzyme activities in horses. Methods: Pulmonary and hepatic tissues from 22 horses that were 4 months to 32 years old. Methods: Pulmonary and hepatic tissues from horses were used to prepare cytosolic (glutathione S-transferase and soluble epoxide hydrolase) and microsomal (cytochrome P450 monooxygenases) enzymes. Rates of microsomal metabolism of ethoxyresorufin, pentoxyresorufin, and naphthalene were determined by high-performance liquid chromatography. Activities of glutathione S-transferase and soluble epoxide hydrolase were determined spectrophotometrically. Cytochrome P450 content was determined by carbon monoxide bound-difference spectrum of dithionite-reduced microsomes. Activity was expressed relative to total protein concentration. Results: Microsomal protein and cytochromeP450 contents were detectable in all horses and did not vary with age. Hepatic ethoxyresorufin metabolism was detected in all horses; by comparison, pulmonary metabolism of ethoxyresorufin and hepatic and pulmonary metabolism of pentoxyresorufin were detected at lower rates. Rate of hepatic naphthalene metabolism remained constant with increasing age, whereas rate of pulmonary naphthalene metabolism was significantly lower in weanlings (ie, horses 4 to 6 months old), compared with adult horses. Hepatic glutathione S-transferase activity (cytosol) increased with age; however, these changes were not significant. Pulmonary glutathione S-transferase activity (cytosol) was significantly lower in weanlings than adult horses. Hepatic and pulmonary soluble epoxide hydrolase did not vary with age of horses. Conclusions: Activity of cytochrome P450 isoforms that metabolize naphthalene and glutathione S-transferases in lungs are significantly lower in weanlings than adult horses, which suggests reduced ability of young horses to metabolize xenobiotics by this organ.
Publication Date: 2000-02-24 PubMed ID: 10685686DOI: 10.2460/ajvr.2000.61.152Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't
  • Research Support
  • U.S. Gov't
  • P.H.S.

Summary

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This research examines the activities of particular enzymes in the lung and liver tissues of horses of varying ages to understand the capacity of these organs to metabolize foreign substances.

Study Design

  • The researchers started by working with lung and liver tissues taken from 22 horses that were between 4 months to 32 years old.
  • The team produced enzymes such as cytochrome P450 monooxygenases, glutathione S-transferase and soluble epoxide hydrolase from these tissues.
  • They used high-performance liquid chromatography to determine the enzyme metabolism rates of substances like ethoxyresorufin, pentoxyresorufin, and naphthalene found in the microsomal enzymes.
  • Using spectrophotometry, they detected the activities of glutathione S-transferase and soluble epoxide hydrolase.
  • The cytochrome P450 content was then found via the carbon monoxide bound-difference spectrum of dithionite-reduced microsomes.
  • Finally, enzyme activity was examined in relation to total protein concentration.

Findings

  • Microsomal protein and cytochrome P450 contents were found in all examined horses and didn’t show variations with age.
  • All horses showed liver metabolism of ethoxyresorufin, while metabolism of ethoxyresorufin in the lungs and pentoxyresorufin metabolism in both lungs and liver were found to occur at a slower pace.
  • Rate of liver naphthalene metabolism did not change with age of the horse but the rate of lung naphthalene metabolism was noteworthy and significantly lower in younger horses (weanlings) between 4 to 6 months old compared to adult horses.
  • Hepatic glutathione S-transferase activity (located in cytosol) increased as horses aged but the rate of increase was not significantly high. The lungs of weanlings, however, registered significantly lower activity of glutathione S-transferase than adult horses.
  • Finally, both the lungs and liver showed no age-related variations in activity when it came to the enzyme soluble epoxide hydrolase.

Conclusions

  • Based on the gathered results, the researchers concluded that the cytochrome P450 isoforms in the lungs, which help to metabolize naphthalene, and lung-based glutathione S-transferases show significantly lower activity in weanlings compared to adult horses.
  • This suggests that younger horses might have a reduced ability to metabolize certain toxic substances, known as xenobiotics, compared to their older counterparts due to a lower enzyme activity in their lungs.

Cite This Article

APA
Lakritz J, Winder BS, Noorouz-Zadeh J, Huang TL, Buckpitt AR, Hammock BD, Plopper CG. (2000). Hepatic and pulmonary enzyme activities in horses. Am J Vet Res, 61(2), 152-157. https://doi.org/10.2460/ajvr.2000.61.152

Publication

ISSN: 0002-9645
NlmUniqueID: 0375011
Country: United States
Language: English
Volume: 61
Issue: 2
Pages: 152-157

Researcher Affiliations

Lakritz, J
  • Department of Anatomy, School of Veterinary Medicine, University of California, Davis 95616, USA.
Winder, B S
    Noorouz-Zadeh, J
      Huang, T L
        Buckpitt, A R
          Hammock, B D
            Plopper, C G

              MeSH Terms

              • Aging / metabolism
              • Animals
              • Cytochrome P-450 CYP1A1 / metabolism
              • Cytochrome P-450 CYP2B1 / metabolism
              • Cytochrome P-450 Enzyme System / metabolism
              • Epoxide Hydrolases / metabolism
              • Glutathione Transferase / metabolism
              • Horses / growth & development
              • Horses / metabolism
              • Liver / enzymology
              • Liver / growth & development
              • Lung / enzymology
              • Lung / growth & development
              • Microsomes / enzymology
              • Microsomes, Liver / enzymology

              Grant Funding

              • ESO 6700 / NIEHS NIH HHS
              • P42 ESO 4699 / NIEHS NIH HHS
              • R01 ES02710 / NIEHS NIH HHS

              Citations

              This article has been cited 7 times.
              1. Shapter FM, Granados-Soler JL, Stewart AJ, Bertin FR, Allavena R. Equine Crofton Weed (Ageratina spp.) Pneumotoxicity: What Do We Know and What Do We Need to Know?. Animals (Basel) 2023 Jun 23;13(13).
                doi: 10.3390/ani13132082pubmed: 37443880google scholar: lookup
              2. Sun CP, Zhang XY, Morisseau C, Hwang SH, Zhang ZJ, Hammock BD, Ma XC. Discovery of Soluble Epoxide Hydrolase Inhibitors from Chemical Synthesis and Natural Products. J Med Chem 2021 Jan 14;64(1):184-215.
                doi: 10.1021/acs.jmedchem.0c01507pubmed: 33369424google scholar: lookup
              3. Guedes A, Galuppo L, Hood D, Hwang SH, Morisseau C, Hammock BD. Soluble epoxide hydrolase activity and pharmacologic inhibition in horses with chronic severe laminitis. Equine Vet J 2017 May;49(3):345-351.
                doi: 10.1111/evj.12603pubmed: 27338788google scholar: lookup
              4. Guedes AG, Morisseau C, Sole A, Soares JH, Ulu A, Dong H, Hammock BD. Use of a soluble epoxide hydrolase inhibitor as an adjunctive analgesic in a horse with laminitis. Vet Anaesth Analg 2013 Jul;40(4):440-8.
                doi: 10.1111/vaa.12030pubmed: 23463912google scholar: lookup
              5. Schmitz A, Portier CJ, Thormann W, Theurillat R, Mevissen M. Stereoselective biotransformation of ketamine in equine liver and lung microsomes. J Vet Pharmacol Ther 2008 Oct;31(5):446-55.
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                doi: 10.1007/s11259-006-3247-ypubmed: 16437303google scholar: lookup
              7. Feng Y, Li M, Zheng Y, Qu H, Li P, Dong B, Wang Y, Liu G, Jia B, Ma Q. Toxicokinetics of a Single Oral Dose of Aflatoxin B(1) in Plasma, Feces, and Urine of Male Donkeys. Toxins (Basel) 2025 Apr 20;17(4).
                doi: 10.3390/toxins17040206pubmed: 40278704google scholar: lookup