FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Veterinary research communications2006; 30(3); 271-283; doi: 10.1007/s11259-006-3247-y

Comparison of hydrolytic and conjugative biotransformation pathways in horse, cattle, pig, broiler chick, rabbit and rat liver subcellullar fractions.

Abstract: To complete a studyaimed at investigating the pattern of the basal activities of liver xenobioticmetabolizing enzymes in major and minor species intended for meat production, microsomal carboxylesterases and some conjugating enzyme activities were determined and compared in liver preparations from horses, cattle, pigs, rabbits and broiler chicks, using the rat as a reference species. Horses and broiler chicks exhibited a lower microsomal carboxylesterase activity towards indophenyl or p-nitrophenyl acetate than that measured in cattle or pig subfractions. Among food-producing species, the rate of glucuronidation of either 1-naphthol or p-nitrophenol was in the order pigs approximately rabbits > horses >> cattle > broiler chicks. The widest variations were observed in the acetylation capacity towards p-aminobenzoic acid or isoniazid, which in rabbits was 3-fold to 11-fold greater than that displayed by any other examined species; low but measurable activities were found in equine and bovine cytosols. The activity of cytosolic glutathione S-transferase (GST) accepting the general substrate 1-chloro-2,4-dinitrobenzene was significantly higher in rabbits, horses and pigs than in rat, broiler chicks and cattle. Finally, an uneven pattern of activity towards the other tested GST substrates - 3,4-dichloronitrobenzene, ethacrinic acid or 1,2-epoxybutane - was observed, possibly reflecting the species-related expression of different GST classes; in this respect, the conjugative capacity displayed by horses was higher than or comparable to that found in the other food-producing species.
Get Full Text
Publication Date: 2006-01-27 PubMed ID: 16437303DOI: 10.1007/s11259-006-3247-yGoogle Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Comparative Study
  • Journal Article

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 explores how the livers of various animals, both major and minor species intended for meat production, process foreign substances. The research highlights distinct patterns in the way these animals’ liver enzymes deal with outside chemicals and substances, potentially impacting our understanding of how different species’ bodies react to drugs and toxins.

Research Objectives and Methods

  • The main aim of the research was to gain understanding of the basic activities of liver enzymes that metabolize xenobiotics in different species.
  • The study involved determining and comparing microsomal carboxylesterases and conjugating enzyme activities in liver preparations from horses, cattle, pigs, rabbits, and broiler chicks, with rats used as a reference species.

Results and Findings

  • Observations showed horses and broiler chicks have lower liver enzyme activity towards indophenyl or p-nitrophenyl acetate than cattle or pig liver subfractions.
  • The glucuronidation rate, a crucial biological process in the body that facilitates the excretion of toxic substances and drugs, was highest in pigs and rabbits, followed by horses, cattle and broiler chicks. This determines how each species’ body would handle excretion of toxins.
  • The acetylation capacity, which is another crucial process in drug metabolism, was highest in rabbits, 3 to 11 times higher than in any other species tested. However, measurable activities were also detected in horse and cattle liver fractions.
  • The activity of cytosolic glutathione S-transferase (GST), an enzyme that plays a significant role in detoxification by catalysing the conjugation of many substances, was found to be higher in rabbits, horses, and pigs than in rats, chicken, and cattle.
  • The team also found varying activity levels towards other tested GST substrates (3,4-dichloronitrobenzene, ethacrinic acid, and 1,2-epoxybutane), possibly due to the species-specific expression of different GST classes. In this aspect, the detoxifying ability of horses was seen to be higher or similar to other food-producing species.

In conclusion, the research provides invaluable insight into the species-specific metabolic activity levels towards xenobiotics. It helps to cement our understanding of the biological processes in different species and how their bodies process foreign substances, potentially impacting drug efficacy or toxicity across diverse species.

Cite This Article

APA
Gusson F, Carletti M, Albo AG, Dacasto M, Nebbia C. (2006). Comparison of hydrolytic and conjugative biotransformation pathways in horse, cattle, pig, broiler chick, rabbit and rat liver subcellullar fractions. Vet Res Commun, 30(3), 271-283. https://doi.org/10.1007/s11259-006-3247-y

Publication

Veterinary research communications
ISSN: 1573-7446
NlmUniqueID: 8100520
Country: Switzerland
Language: English
Volume: 30
Issue: 3
Pages: 271-283

Researcher Affiliations

Gusson, F
  • Department of Animal Pathology, Division of Pharmacology and Toxicology, University of Turin, Via Leonardo da Vinci 44, I-10095, Grugliasco.
Carletti, M
    Albo, A Giuliano
      Dacasto, M
        Nebbia, C

          MeSH Terms

          • Acetyltransferases / metabolism
          • Animals
          • Biotransformation / physiology
          • Liver / enzymology
          • Microsomes, Liver / enzymology
          • Species Specificity
          • Substrate Specificity
          • Xenobiotics / metabolism

          References

          This article includes 37 references
          1. Nebbia C. Biotransformation enzymes as determinants of xenobiotic toxicity in domestic animals.. Vet J 2001 May;161(3):238-52.
            pubmed: 11352482doi: 10.1053/tvjl.2000.0561google scholar: lookup
          2. Geisler SA, Olshan AF. GSTM1, GSTT1, and the risk of squamous cell carcinoma of the head and neck: a mini-HuGE review.. Am J Epidemiol 2001 Jul 15;154(2):95-105.
            pubmed: 11447041doi: 10.1093/aje/154.2.95google scholar: lookup
          3. Hayes JD, Milner SW, Walker SW. Expression of glyoxalase, glutathione peroxidase and glutathione S-transferase isoenzymes in different bovine tissues.. Biochim Biophys Acta 1989 Jan 19;994(1):21-9.
            pubmed: 2909253doi: 10.1016/0167-4838(89)90057-5google scholar: lookup
          4. Juskevich JC. Comparative metabolism in food-producing animals: programs sponsored by the Center for Veterinary Medicine.. Drug Metab Rev 1987;18(2-3):345-62.
            pubmed: 3330521doi: 10.3109/03602538708998312google scholar: lookup
          5. Antoine B, Boutin JA, Siest G. Further validation of the Mulder and van Doorn kinetic procedure for the measurement of microsomal UDP-glucuronosyltransferase activities.. Biochem J 1988 Jun 15;252(3):930-1.
            pubmed: 3138979doi: 10.1042/bj2520930google scholar: lookup
          6. Rouimi P, Anglade P, Debrauwer L, Tulliez J. Characterization of pig liver glutathione S-transferases using HPLC-electrospray-ionization mass spectrometry.. Biochem J 1996 Aug 1;317 ( Pt 3)(Pt 3):879-84.
            pubmed: 8760377doi: 10.1042/bj3170879google scholar: lookup
          7. D'Silva C. Inhibition and recognition studies on the glutathione-binding site of equine liver glutathione S-transferase.. Biochem J 1990 Oct 1;271(1):161-5.
            pubmed: 2222409doi: 10.1042/bj2710161google scholar: lookup
          8. Baars AJ, Jansen M, Breimer DD. The influence of phenobarbital, 3-methylcholanthrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin on glutathione S-transferase activity of rat liver cytosol.. Biochem Pharmacol 1978;27(21):2487-97.
            pubmed: 728202doi: 10.1016/0006-2952(78)90314-3google scholar: lookup
          9. Kuilman ME, Maas RF, Fink-Gremmels J. Cytochrome P450-mediated metabolism and cytotoxicity of aflatoxin B(1) in bovine hepatocytes.. Toxicol In Vitro 2000 Aug;14(4):321-7.
            pubmed: 10906438doi: 10.1016/s0887-2333(00)00025-4google scholar: lookup
          10. Lakritz J, Winder BS, Noorouz-Zadeh J, Huang TL, Buckpitt AR, Hammock BD, Plopper CG. Hepatic and pulmonary enzyme activities in horses.. Am J Vet Res 2000 Feb;61(2):152-7.
            pubmed: 10685686doi: 10.2460/ajvr.2000.61.152google scholar: lookup
          11. Ugazio G, Burdino E, Dacasto M, Bosio A, van't Klooster G, Nebbia C. Induction of hepatic drug metabolizing enzymes and interaction with carbon tetrachloride in rats after a single oral exposure to atrazine.. Toxicol Lett 1993 Sep;69(3):279-88.
            pubmed: 8212068doi: 10.1016/0378-4274(93)90033-tgoogle scholar: lookup
          12. Habig WH, Pabst MJ, Jakoby WB. Glutathione S-transferases. The first enzymatic step in mercapturic acid formation.. J Biol Chem 1974 Nov 25;249(22):7130-9.
            pubmed: 4436300
          13. Radominska-Pandya A, Czernik PJ, Little JM, Battaglia E, Mackenzie PI. Structural and functional studies of UDP-glucuronosyltransferases.. Drug Metab Rev 1999 Nov;31(4):817-99.
            pubmed: 10575553doi: 10.1081/dmr-100101944google scholar: lookup
          14. Coulet M, Eeckhoutte C, Galtier P. Ontogenic development of drug-metabolizing enzymes in male chicken liver.. Can J Physiol Pharmacol 1996 Jan;74(1):32-7.
            pubmed: 8963950
          15. Kaddouri M, Larrieu G, Eeckhoutte C, Galtier P. The development of drug-metabolizing enzymes in female sheep livers.. J Vet Pharmacol Ther 1990 Dec;13(4):340-9.
            pubmed: 2287026doi: 10.1111/j.1365-2885.1990.tb00787.xgoogle scholar: lookup
          16. Jokanović M. Biotransformation of organophosphorus compounds.. Toxicology 2001 Sep 25;166(3):139-60.
            pubmed: 11543910doi: 10.1016/s0300-483x(01)00463-2google scholar: lookup
          17. Hayes JD, Judah DJ, McLellan LI, Neal GE. Contribution of the glutathione S-transferases to the mechanisms of resistance to aflatoxin B1.. Pharmacol Ther 1991;50(3):443-72.
            pubmed: 1754606doi: 10.1016/0163-7258(91)90053-ogoogle scholar: lookup
          18. Zemaitis MA, Greene FE. In vivo and in vitro effects of thiuram disulfides and dithiocarbamates on hepatic microsomal drug metabolism in the rat.. Toxicol Appl Pharmacol 1979 Apr;48(2):343-50.
            pubmed: 224526doi: 10.1016/0041-008x(79)90041-3google scholar: lookup
          19. Court MH. Acetaminophen UDP-glucuronosyltransferase in ferrets: species and gender differences, and sequence analysis of ferret UGT1A6.. J Vet Pharmacol Ther 2001 Dec;24(6):415-22.
            pubmed: 11903872doi: 10.1046/j.1365-2885.2001.00366.xgoogle scholar: lookup
          20. Satoh T, Hosokawa M. Molecular aspects of carboxylesterase isoforms in comparison with other esterases.. Toxicol Lett 1995 Dec;82-83:439-45.
            pubmed: 8597091doi: 10.1016/0378-4274(95)03493-5google scholar: lookup
          21. Hsieh CH, Liu LF, Tsai SP, Tam MF. Characterization and cloning of avian-hepatic glutathione S-transferases.. Biochem J 1999 Oct 1;343 Pt 1(Pt 1):87-93.
            pubmed: 10493915
          22. Van Duijkeren E, Vulto AG, Van Miert AS. Trimethoprim/sulfonamide combinations in the horse: a review.. J Vet Pharmacol Ther 1994 Feb;17(1):64-73.
            pubmed: 8196097doi: 10.1111/j.1365-2885.1994.tb00524.xgoogle scholar: lookup
          23. Primiano T, Novak RF. Purification and characterization of class mu glutathione S-transferase isozymes from rabbit hepatic tissue.. Arch Biochem Biophys 1993 Mar;301(2):404-10.
            pubmed: 8460949doi: 10.1006/abbi.1993.1163google scholar: lookup
          24. Sheehan D, Meade G, Foley VM, Dowd CA. Structure, function and evolution of glutathione transferases: implications for classification of non-mammalian members of an ancient enzyme superfamily.. Biochem J 2001 Nov 15;360(Pt 1):1-16.
            pubmed: 11695986doi: 10.1042/0264-6021:3600001google scholar: lookup
          25. Nebbia C, Dacasto M, Carletti M. Postnatal development of hepatic oxidative, hydrolytic and conjugative drug-metabolizing enzymes in female horses.. Life Sci 2004 Feb 13;74(13):1605-19.
            pubmed: 14738905doi: 10.1016/j.lfs.2003.08.028google scholar: lookup
          26. Meyer UA, Zanger UM. Molecular mechanisms of genetic polymorphisms of drug metabolism.. Annu Rev Pharmacol Toxicol 1997;37:269-96.
            pubmed: 9131254doi: 10.1146/annurev.pharmtox.37.1.269google scholar: lookup
          27. Trepanier LA, Ray K, Winand NJ, Spielberg SP, Cribb AE. Cytosolic arylamine N-acetyltransferase (NAT) deficiency in the dog and other canids due to an absence of NAT genes.. Biochem Pharmacol 1997 Jul 1;54(1):73-80.
            pubmed: 9296352doi: 10.1016/s0006-2952(97)00140-8google scholar: lookup
          28. Nebbia C, Dacasto M, Rossetto Giaccherino A, Giuliano Albo A, Carletti M. Comparative expression of liver cytochrome P450-dependent monooxygenases in the horse and in other agricultural and laboratory species.. Vet J 2003 Jan;165(1):53-64.
            pubmed: 12618071doi: 10.1016/s1090-0233(02)00174-0google scholar: lookup
          29. LOWRY OH, ROSEBROUGH NJ, FARR AL, RANDALL RJ. Protein measurement with the Folin phenol reagent.. J Biol Chem 1951 Nov;193(1):265-75.
            pubmed: 14907713
          30. Eaton DL, Bammler TK. Concise review of the glutathione S-transferases and their significance to toxicology.. Toxicol Sci 1999 Jun;49(2):156-64.
            pubmed: 10416260doi: 10.1093/toxsci/49.2.156google scholar: lookup
          31. Hosokawa M, Maki T, Satoh T. Multiplicity and regulation of hepatic microsomal carboxylesterases in rats.. Mol Pharmacol 1987 Jun;31(6):579-84.
            pubmed: 3600603
          32. Watkins JB 3rd, Klaassen CD. Xenobiotic biotransformation in livestock: comparison to other species commonly used in toxicity testing.. J Anim Sci 1986 Sep;63(3):933-42.
            pubmed: 3759720doi: 10.2527/jas1986.633933xgoogle scholar: lookup
          33. Nousiainen U, Törrönen R, Hänninen O. Differential induction of various carboxylesterases by certain polycyclic aromatic hydrocarbons in the rat.. Toxicology 1984 Sep 14;32(3):243-51.
            pubmed: 6089379doi: 10.1016/0300-483x(84)90077-5google scholar: lookup
          34. Chauret N, Gauthier A, Martin J, Nicoll-Griffith DA. In vitro comparison of cytochrome P450-mediated metabolic activities in human, dog, cat, and horse.. Drug Metab Dispos 1997 Oct;25(10):1130-6.
            pubmed: 9321515
          35. Sivapathasundaram S, Sauer MJ, Ioannides C. Xenobiotic conjugation systems in deer compared with cattle and rat.. Comp Biochem Physiol C Toxicol Pharmacol 2003 Jan;134(1):169-73.
            pubmed: 12524029doi: 10.1016/s1532-0456(02)00224-7google scholar: lookup
          36. Atterberry TT, Burnett WT, Chambers JE. Age-related differences in parathion and chlorpyrifos toxicity in male rats: target and nontarget esterase sensitivity and cytochrome P450-mediated metabolism.. Toxicol Appl Pharmacol 1997 Dec;147(2):411-8.
            pubmed: 9439736doi: 10.1006/taap.1997.8303google scholar: lookup
          37. Short CR, Flory W, Hsieh LC, Aranas T, Ou SP, Weissinger J. Comparison of hepatic drug metabolizing enzyme activities in several agricultural species.. Comp Biochem Physiol C Comp Pharmacol Toxicol 1988;91(2):419-24.
            pubmed: 2905957doi: 10.1016/0742-8413(88)90053-9google scholar: lookup

          Citations

          This article has been cited 15 times.
          1. Ichinose P, Miró MV, Larsen K, Lanusse C, Lifschitz A, Virkel G. Medication with fenbendazole in feed: plasma concentrations and effects on hepatic xenobiotic metabolizing enzymes in swine. Vet Res Commun 2023 Jun;47(2):803-815.
            doi: 10.1007/s11259-022-10041-6pubmed: 36542192google scholar: lookup
          2. Cantiello M, Carletti M, Giantin M, Gardini G, Capolongo F, Cascio P, Pauletto M, Girolami F, Dacasto M, Nebbia C. Induction by Phenobarbital of Phase I and II Xenobiotic-Metabolizing Enzymes in Bovine Liver: An Overall Catalytic and Immunochemical Characterization. Int J Mol Sci 2022 Mar 24;23(7).
            doi: 10.3390/ijms23073564pubmed: 35408925google scholar: lookup
          3. Rychen G, Aquilina G, Azimonti G, Bampidis V, Bastos ML, Bories G, Cocconcelli PS, Flachowsky G, Gropp J, Kolar B, Kouba M, López Puente S, López-Alonso M, Mantovani A, Mayo B, Ramos F, Saarela M, Villa RE, Wallace RJ, Wester P, Brantom P, Dusemund B, Hogstrand C, Van Beelen P, Westendorf J, Gregoretti L, Manini P, Chesson A. Safety and efficacy of aryl-substituted primary alcohol, aldehyde, acid, ester and acetal derivatives belonging to chemical group 22 when used as flavourings for all animal species. EFSA J 2017 Feb;15(2):e04672.
            doi: 10.2903/j.efsa.2017.4672pubmed: 32625398google scholar: lookup
          4. Rychen G, Aquilina G, Azimonti G, Bampidis V, de Lourdes Bastos M, Bories G, Cocconcelli PS, Flachowsky G, Gropp J, Kolar B, Kouba M, López Puente S, López-Alonso M, Mantovani A, Mayo B, Ramos F, Saarela M, Villa RE, Wallace RJ, Wester P, Brantom P, Dusemund B, Hogstrand C, Van Beelen P, Westendorf J, Gregoretti L, Manini P, Chesson A. Safety and efficacy of pyrazine derivatives including saturated ones belonging to chemical group 24 when used as flavourings for all animal species. EFSA J 2017 Feb;15(2):e04671.
            doi: 10.2903/j.efsa.2017.4671pubmed: 32625397google scholar: lookup
          5. Gleich A, Kaiser B, Honscha W, Fuhrmann H, Schoeniger A. Evaluation of the hepatocyte-derived cell line BFH12 as an in vitro model for bovine biotransformation. Cytotechnology 2019 Feb;71(1):231-244.
            doi: 10.1007/s10616-018-0279-4pubmed: 30617848google scholar: lookup
          6. León Z, de Vlieger J, Chisvert A, Salvador A, Lingeman H, Irth H, Giera M. Identification of the Biotransformation Products of 2-Ethylhexyl 4-(N,N-Dimethylamino)benzoate. Chromatographia 2010 Jan;71(1-2):55-63.
            doi: 10.1365/s10337-009-1386-3pubmed: 20062819google scholar: lookup
          7. Sahin Z, Sonmez F, Avci D, Duran T, Darwich NA, Banerjee B. Bioactive Potential of Cydonia oblonga and Diospyros kaki Vinegars: Phenolic Content, Antioxidant and GST Inhibitory Activity, and Molecular Docking Studies. Biomed Res Int 2025;2025:6699595.
            doi: 10.1155/bmri/6699595pubmed: 41347041google scholar: lookup
          8. Serrano-Rodríguez JM, Miraz R, Saitua A, Díez de Castro E, Ledesma-Escobar C, Ferreiro-Vera C, Priego-Capote F, Sánchez de Medina V, Sánchez de Medina A. Metabolism, pharmacokinetics, and bioavailability of cannabigerol in horses following intravenous and oral administration with micellar and oil formulations. Front Vet Sci 2025;12:1688214.
            doi: 10.3389/fvets.2025.1688214pubmed: 41234397google scholar: lookup
          9. Villa RE, Azimonti G, Bonos E, Christensen H, Durjava M, Dusemund B, Gehring R, Glandorf B, Kouba M, López-Alonso M, Marcon F, Nebbia C, Pechová A, Prieto-Maradona M, Röhe I, Theodoridou K, Bastos M, Poiger T, Galobart J, Manini P, Tarrès-Call J, Vettori MV, Pizzo F. Safety and efficacy of a feed additive consisting of 4-hydroxy-2,5-dimethylfuran-3(2H)-one for all animal species other than dogs and cats (ADISSEO France SAS, ADM International Sàrl, Laboratoires Phodé S.A.S., LUCTA S.A., Norel, S.A.). EFSA J 2025 Jul;23(7):e9538.
            doi: 10.2903/j.efsa.2025.9538pubmed: 40671839google scholar: lookup
          10. . Safety and efficacy of secondary alicyclic saturated and unsaturated alcohols, ketones, ketals and esters with ketals containing alicyclic alcohols or ketones and esters containing secondary alicyclic alcohols from chemical group 8 when used as flavourings for all animal species. EFSA J 2016 Jun;14(6):e04475.
            doi: 10.2903/j.efsa.2016.4475pubmed: 40007846google scholar: lookup
          11. . Safety and efficacy of thiazoles, thiophene and thiazoline belonging to chemical group 29 when used as flavourings for all animal species. EFSA J 2016 Jun;14(6):e04441.
            doi: 10.2903/j.efsa.2016.4441pubmed: 40007844google scholar: lookup
          12. . Safety and efficacy of α,β-unsaturated straight-chain and branched-chain aliphatic primary alcohols, aldehydes, acids and esters belonging to chemical group 3 when used as flavourings for all animal species. EFSA J 2016 Jun;14(6):e04512.
            doi: 10.2903/j.efsa.2016.4512pubmed: 40007828google scholar: lookup
          13. Bampidis V, Azimonti G, Bastos ML, Christensen H, Durjava M, Kouba M, López-Alonso M, Puente SL, Marcon F, Mayo B, Pechová A, Petkova M, Ramos F, Villa RE, Woutersen R, Brantom P, Chesson A, Schlatter J, Westendorf J, Dirven Y, Manini P, Dusemund B. Safety and efficacy of a feed additive consisting of a tincture derived from the roots of Panax ginseng C.A.Mey. (ginseng tincture) for horses, dogs and cats (FEFANA asbl). EFSA J 2024 Apr;22(4):e8730.
            doi: 10.2903/j.efsa.2024.8730pubmed: 38591023google scholar: lookup
          14. Sun P, Lootens O, Kabeta T, Reckelbus D, Furman N, Cao X, Zhang S, Antonissen G, Croubels S, De Boevre M, De Saeger S. Exploration of Cytochrome P450-Related Interactions between Aflatoxin B1 and Tiamulin in Broiler Chickens. Toxins (Basel) 2024 Mar 20;16(3).
            doi: 10.3390/toxins16030160pubmed: 38535826google scholar: lookup
          15. Amminikutty N, Spalenza V, Jarriyawattanachaikul W, Badino P, Capucchio MT, Colombino E, Schiavone A, Greco D, D'Ascanio V, Avantaggiato G, Dabbou S, Nebbia C, Girolami F. Turmeric Powder Counteracts Oxidative Stress and Reduces AFB1 Content in the Liver of Broilers Exposed to the EU Maximum Levels of the Mycotoxin. Toxins (Basel) 2023 Dec 7;15(12).
            doi: 10.3390/toxins15120687pubmed: 38133191google scholar: lookup
          Subscribe to our newsletter
          Join 99,850 horse owners like you who receive our email updates on horse health and nutrition.