INVESTIGATION OF ZONULIN LEVELS IN DOGS INFECTED WITH CANINE DISTEMPER VIRUS

Year 2024, Volume: 5 Issue: 2, 55 - 61

Ethem Mert Çöllü , Tahir Özalp , Songül Erdoğan , Kerem Ural , Hasan Erdoğan

https://doi.org/10.58833/bozokvetsci.1545898

Abstract

This study aims to investigate the impact of Canine Distemper Virus (CDV) infection on plasma zonulin levels, focusing particularly on how this effect varies in patients exhibiting neurological symptoms. The research involved the evaluation of 20 infected dogs and 10 healthy control dogs, all of which were brought to the Internal Medicine Clinics of Aydın Adnan Menderes University Veterinary Faculty for diagnosis and treatment. The zonulin levels in the infected dogs were found to be significantly higher compared to the healthy controls. These findings suggest that the virus affects not only the gastrointestinal barrier but also the blood-brain barrier. This supports the hypothesis that these changes may contribute to the increased permeability of the blood-brain barrier.

Keywords

Distemper, Dog, Gut permeability, Zonulin

Project Number

This study was supported by the Scientific Research Projects Unit of Aydın Adnan Menderes University under project number VTF – 23022.

KANİN DİSTEMPER VİRUS İLE ENFEKTE KÖPEKLERDE ZONULİN SEVİYELERİNİN ARAŞTIRILMASI

Abstract

Bu çalışma, Canine Distemper Virüs (CDV) enfeksiyonunun plazma zonulin seviyeleri üzerindeki etkisini, özellikle nörolojik semptomlar gösteren hastalarda nasıl değiştiğini araştırmayı amaçlamaktadır. Araştırmada, Aydın Adnan Menderes Üniversitesi Veteriner Fakültesi İç Hastalıkları Klinikleri’ ne tanı ve tedavi için getirilen 20 enfekte köpek ve 10 sağlıklı kontrol köpeği değerlendirilmiştir. Enfekte köpeklerde zonulin seviyeleri, sağlıklı kontrollerden anlamlı derecede yüksek bulunmuştur. Bu bulgular, virüsün sadece gastrointestinal bariyeri değil, aynı zamanda kan-beyin bariyerini de etkilediğini önermektedir. Bu değişikliklerin kan-beyin bariyerinin artan geçirgenliğine katkıda bulunabileceği hipotezini desteklemektedir.

Keywords

Bağırsak geçirgenliği, Distemper, Köpek, Zonulin.

Ethical Statement

adü hadyek 64583101/2022/74

Supporting Institution

This study was supported by the Scientific Research Projects Unit of Aydın Adnan Menderes University under project number VTF – 23022.

Project Number

This study was supported by the Scientific Research Projects Unit of Aydın Adnan Menderes University under project number VTF – 23022.

References

• 1. Newbury S, Larson LJ, Schultz RD. Canine Distemper Virus. In: Infectious Disease Management in Animal Shelters, Wiley and Blackwell, 2009, p.161-173.
• 2. De Nardo TF, Bertolo PH, Bernardes PA, Munari DP, Machado GF, Jardim LS, et al. Contribution of astrocytes and macrophage migration inhibitory factor to immune-mediated canine encephalitis caused by the distemper virus. Veterinary immunology and immunopathology, 2020, 221, 110010.
• 3. Camara-Lemarroy CR, Silva C, Greenfield J, Liu WQ, Metz LM, Yong VW. Biomarkers of intestinal barrier function in multiple sclerosis are associated with disease activity. Multiple Sclerosis Journal, 2020, 26(11), 1340-1350.
• 4. Zißler J, Rothhammer V, Linnerbauer M. Gut–Brain Interactions and Their Impact on Astrocytes in the Context of Multiple Sclerosis and Beyond. Cells, 2024, 13(6), 497.
• 5. Veres-Székely A, Szász C, Pap D, Szebeni B, Bokrossy P, Vannay Á. Zonulin as a potential therapeutic target in microbiota-gut-brain axis disorders: encouraging results and emerging questions. International journal of molecular sciences, 2023, 24(8), 7548.
• 6. Arrieta MC, Bistritz L, Meddings JB. Alterations in intestinal permeability. Gut, 2006, 55(10), 1512-1520.
• 7. Sapone A, de Magistris L, Pietzak M, Clemente MG, Tripathi A, Cucca F, et al. Zonulin upregulation is associated with increased gut permeability in subjects with type 1 diabetes and their relatives. Diabetes, 2006, 55(5), 1443-1449.
• 8. Fasano A. Intestinal permeability and its regulation by zonulin: diagnostic and therapeutic implications. Clinical Gastroenterology and Hepatology, 2012, 10(10), 1096-1100.
• 9. Sturgeon C, Fasano A. Zonulin, a regulator of epithelial and endothelial barrier functions and its involvement in chronic inflammatory diseases. Tissue barriers, 2016, 4(4), e1251384.
• 10. Noris M, Benigni A, Remuzzi G. The case of complement activation in COVID-19 multiorgan impact. Kidney international, 2020, 98(2), 314-322.
• 11. Rittirsch D, Flierl MA, Nadeau BA, Day DE, Huber-Lang MS, Grailer JJ, et al. Zonulin as prehaptoglobin2 regulates lung permeability and activates the complement system. American Journal of Physiology-Lung Cellular and Molecular Physiology, 2013, 304(12), L863-L872.
• 12. Llorens S, Nava E, Muñoz-López M, Sánchez-Larsen Á, Segura T. Neurological Symptoms of COVID-19: The Zonulin Hypothesis. Frontiers in immunology, 2021, 12, 665300.
• 13. Widera D, Martínez Aguilar R, Cottrell GS. Toll-Like Receptor 4 and Protease-Activated Receptor 2 in Physiology and Pathophysiology of the Nervous System: More Than Just Receptor Cooperation?. Neural Regeneration Research, 2019, 14(7), 1196-1201.
• 14. Bocsik A, Walter FR, Gyebrovszki A, Fülöp L, Blasig I, Dabrowski S. Reversible Opening of Intercellular Junctions of Intestinal Epithelial and Brain Endothelial Cells With Tight Junction Modulator Peptides. Journal of Pharmaceutical Sciences, 2016, 105(2), 754-765.
• 15. Amude AM, Alfieri AA, Balarin MRS, Faria dos Reis AC, Alfieri AF. Cerebrospinal fluid from a 7-month-old dog with seizure-like episodes. Veterinary Clinical Pathology Journal, 2006a, 35, 119-122.
• 16. Tipold A, Vandevelde M, Jaggy A. Neurological manifestations of canine distemper virus infection. Journal of Small Animal Practice, 1992, 33(10), 466-470.
• 17. Amude AM, Carvalho GA, Balarin MRS, Arias MVB, Faria dos Reis AC, Alfieri AA, et al. Canine distemper encephalomyelitis in dogs without systemic signs of the disease – preliminary studies in three cases. Clinica Veterinaria, 2006b, 60, 60-66.
• 18. Dewey CW. Practical Guide To Canine and Feline Neurology (2nd ed.). Ames, Iowa, USA: Wiley Blackwell, 2008.
• 19. Amude AM, Alfieri AA, Arias MVB, Alfieri AF. Clinical syndromes of nervous distemper in dogs initially presented without conventional evidences of CDV infection. Semina-Ciencias Agrarias, 2012, 33(6), 2347-2358.
• 20. Schobesberger M, Summerfield A, Doherr MG, Zurbriggen A, Griot C. Canine distemper virus-induced depletion of uninfected lymphocytes is associated with apoptosis. Vet Immunology & Immunopathology, 2005, 104, 33-44.
• 21. Elia G, Camero M, Losurdo M, Lucente MS, Larocca V, Martella V, et al. Virological and serological findings in dogs with naturally occurring distemper. Journal of virological methods, 2015, 213, 127-130.
• 22. Koutinas AF, Polizopoulou ZS, Baumgaertner W, Lekkas S, Kontos V. Relation of clinical signs to pathological changes in 19 cases of canine distemper encephalomyelitis. Journal of comparative pathology, 2002, 126(1), 47-56.
• 23. Gebara CMS, Wosiacki SR, Negrao FJ, de Oliveira DB, Beloni SNE, Alfieri AA. Detection of canine distemper virus nucleoprotein gene by RT-PCR in urine of dogs with distemper clinical signs. Arquivo Brasileiro de Medicina Veterinaria e Zootecnia, 2004, 56(4), 480-487.
• 24. Martella V, Elia G, Buonavoglia C. Canine distemper virus. Veterinary Clinics of North America: Small Animal Practice, 2008, 38(4), 787-797.
• 25. Zhao J, Shi N, Sun Y, Martella V, Nikolin V, Zhu C. Pathogenesis of canine distemper virus in experimentally infected raccoon dogs, foxes and minks. Antiviral Research, 2015, 122(1), 11.
• 26. Saaed MM, Al-Obaidi QT. Clinical, Hematological and Some Biochemical Changes in Dogs Infected With Canine Distemper. Journal of Agriculture and Veterinary Science, 2021, 14(5), 26-33.
• 27. Buragohain M, Goswami S, Kalita DJ. Clinicopathological findings of canine distemper virus infection in dogs. Journal of Entomology and Zoology Studies, 2017, 5(6), 1817-1819.
• 28. Beineke A, Puff C, Seehusen F, Baumgärtner W. Pathogenesis and Immunopathology of Systemic and Nervous Canine Distemper. Veterinary Immunology & Immunopathology, 2009, 127, 1-18.
• 29. Berghoff N, Steiner JM. Laboratory tests for the diagnosis and management of chronic canine and feline enteropathies. Veterinary Clinics of North America-Small Animal Practice, 2011, 41, 311-328. 30. Yama T, Rajesh JB, Prasad H, Rajkhowa TK, Sarma K, Roychoudhury P, et al. Scholarly View of Canine Distemper Cases in Mizoram. International Journal of Current Microbiology and Applied Sciences, 2020, 9(9), 3260-3266.
• 31. Devi T, Asokkumar M, Bharathi MV, Ramesh A. Prognostic Factorial Index for Dogs with Canine Distemper. Indian Journal of Animal Research, 2024, 1(5).
• 32. Bohn AA. Diagnosis of disorders of iron metabolism in dogs and cats. Veterinary Clinics of North America-Small Animal Practice, 2013, 43(6), 1319-1330.
• 33. Carter CM. Alterations in Blood Components. Comprehensive Toxicology, 2018, 249-293.
• 34. Headley SA, Sukura A. Naturally occurring systemic canine distemper virus infection in a pup. Brazilian Journal of Veterinary Pathology, 2009, 2(2), 95-101.
• 35. Vandevelde M, Zurbriggen A, Higgins RJ, Palmer D. Spread and distribution of viral antigen in nervous canine distemper. Acta neuropathologica, 1985, 67(3-4), 211-218.
• 36. Müller CF, Fatzer RS, Beck K, Vandevelde M, Zurbriggen A. Studies on canine distemper virus persistence in the central nervous system. Acta Neuropathologica, 1995, 89(5), 438-445.
• 37. Delucchi L, Fraga M, Zunino P. Effect of the probiotic Lactobacillus murinus LbP2 on clinical parameters of dogs with distemper-associated diarrhea. Canadian Journal of Veterinary Research, 2017, 81(2), 118-121.
• 38. Paul AEH, Stayt J. The intestinal microbiome in dogs and cats with diarrhoea as detected by a faecal polymerase chain reaction‐based panel in Perth, Western Australia. Australian veterinary journal, 2019, 97(10), 418-421.
• 39. Şardağ D. Köpeklerde gastroenteritise neden olan bazı enfeksiyöz ve non-enfeksiyöz hastalıklarda serum ve fekal zonulin seviyelerinin tespiti. Doktora Tezi, Aydın Adnan Menderes Üniversitesi Sağlık Bilimleri Enstitüsü, 2022.
• 40. Macfarlane S, Dillon JF. Microbial biofilms in the human gastrointestinal tract. Journal of applied microbiology, 2007, 102(5), 1187-1196.
• 41. O’Hara JR, Ho W, Linden DR, Mawe GM, Sharkey KA. Enteroendocrine cells and 5-HT availability are altered in mucosa of guinea pigs with TNBS ileitis. American Journal of Physiology Liver Physiology, 2004, 287, 998-1007.
• 42. Rhee SH, Pothoulakis C, Mayer EA. Principles and clinical implications of the brain gut enteric microbiota axis. Nature Reviews Gastroenterology & Hepatology, 2009, 6, 306-314.
• 43. Idris F, Muharram SH, Zaini Z, Alonso S, Diah S. Invasion of a Murine in Vitro Blood-Brain Barrier Co-Culture Model by Dengue Virus Serotypes 1 to 4. Archives of Virology, 2019, 164(4), 1069-1083. doi: 10.1007/s00705-019-04175-3.
• 44. Robinson CP, Busl KM. Neurologic Manifestations of Severe Respiratory Viral Contagions. Critical Care Explorations Journal, 2020, 2(4), 107.
• 45. Daneman R, Rescigno M. The Gut Immune Barrier and the Blood-Brain Barrier: Are They So Different?. Immunity, 2009, 31(5), 722-735.
• 46. Zlokovic BV. The Blood-Brain Barrier in Health and Chronic Neurodegenerative Disorders. Neuron, 2008, 57(2), 178-201.
• 47. Sweeney MD, Zhao Z, Montagne A, Nelson AR, Zlokovic BV. Blood-Brain Barrier: From Physiology to Disease and Back. Physiological Reviews, 2019, 99(1), 21-78.
• 48. Chancharoenthana W, Leelahavanichkul A, Ariyanon W, Vadcharophaswattanakul S, Kamolratanakul S. Leaky gut syndrome is associated with endotoxemia and serum (1→3)-β-D-Glucan in severe dengue infection. Microorganisms, 2021, 9(11), 2390.
• 49. Giron LB, Dweep H, Yin X, Wang H, Damra M, Goldman AR. Plasma markers of disrupted gut permeability in severe COVID-19 patients. Frontiers in Immunology, 2021, 12, 779064. doi: 10.3389/fimmu.2021.686240.
• 50. Rahman MT, Ghosh C, Hossain M, Linfield D, Rezaee F, Janigro D, et al. IFN-γ, IL-17A, or zonulin rapidly increase the permeability of the blood-brain and small intestinal epithelial barriers: Relevance for neuro-inflammatory diseases. Biochemical and Biophysical Research Communications, 2018, 507(1-4), 274-279.
• 51. Şahin N. Gastrointestinal inflamasyonlu köpeklerde serum diamin oksidaz, zonulin, laktat ve D-dimer seviyelerinin tespiti. Doktora Tezi, Aydın Adnan Menderes Üniversitesi Sağlık Bilimleri Enstitüsü, 2023.
• 52. Şen T. İshalli köpeklerde gastrointestinal biyobelirteçlerin araştırılması. Yüksek Lisans Tezi, Aydın Adnan Menderes Üniversitesi Sağlık Bilimleri Enstitüsü, 2021.