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Evaluation of the effects of ribavirin and proanthocyanidin on the clinical outcome, hematological and biochemical parameters, and viral shedding in canine distemper

Year 2023, , 125 - 135, 27.03.2023

Şükrü Değirmençay

https://doi.org/10.46810/tdfd.1244940

Abstract

This study investigated the effects of ribavirin, proanthocyanidin, and ribavirin-proanthocyanidin in dogs naturally infected with canine distemper virus (CDV). Five groups were created, each with six dogs aged 2-6 months: one healthy control group and four patient groups. For ten days, the A group received classical treatment (CT) [fluid treatment and antibiotic], the A+R group received CT + ribavirin, the A+P group received CT + proanthocyanidin, A+R+P group received CT + ribavirin-proanthocyanidin. On days T0, T3, T7, and T10, hematological, biochemical, and clinical scores were done. These days and the fifth and tenth post-treatment days were also screened for CDV. Clinical improvement was best in the A+P, A+R, A, and A+R+P groups, respectively. The A+R group had fewer leucocytes, neutrophils, and monocytes (P<0.05). CK and CK-MB activity were significantly higher only in the A group (P<0.01), and decreased only in the A+R group as therapy progressed. CREA values were high in A+P and A+R groups (P<0.01). The lowest Ca value was in the A+R group (P<0.01). The least CDV presence was detected in the A+R group regarding viral shedding. As a result, using ribavirin or proanthocyanidin helped to lessen the severity of clinical findings, increase survival, and reduce viral shedding in dogs with CDV.

Keywords

antiviral ajanlar canine distemper virus proantosiyanidinler ribavirin.

Thanks

The author would like to express his gratitude to his thesis advisor, Prof. Dr M. Sinan Aktaş, for his guidance. The study's virological analysis was carried out by Assoc. Prof. Dr Mehmet Özkan Timurkan, for which the author is grateful.

References

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  • Kingsbury DW. Paramyxoviridae. Intervirology. 1978;10(3):137–52.
  • Greene CE, Vandevelde M. Canine distemper. In: Greene CE, editor. Infectious diseases of the dog and cat. 4 th. St Louis,: Saunders; 2012. p. 25–42.
  • Sykes JE. Canine distemper virus infection. In: Sykes JE, editor. Canine and feline infectious diseases. 1 st. St Louis: Saunders; 2014. p. 152–65.
  • Leisewitz AL, Carter A, van Vuuren M, van Blerk L. Canine distemper infections, with special reference to South Africa, with a review of the literature. J S Afr Vet Assoc. 2001;72(3):127–36. Martella V, Elia G, Buonavoglia C. Canine distemper virus. Vet Clin North Am Small Anim Pr. 2008;38(4):787–97, vii–viii.
  • Taylor S. Encephalitis, myelitis and meningitis. In: Couto CG, Nelson RW, editors. Small Animal Internal Medicine. 4th ed. St. Louis, Missouri: Mosby Elsevier; 2009. p. 1059–62.
  • Krakowka S, Axthelm MK, Johnson GC. Canine distemper virus. In: Olsen RG, Krakowka S, Blakeslee JR, editors. Comparative Pathobiology of Viral Diseases. Boca Raton: CRC Press; 1985. p. 137–64.
  • Shell LG. Canine distemper. Compend Contin Educ Pract Vet. 1990;12(2):173–9.
  • Ezeibe MCO, Udegbunam RI. Haematology of dogs infected with canine distemper virus. Sokoto J Vet Sci. 2008;7(2):32.
  • Greene GE, Appel M. Canine Distemper Virus. In: Greene GE, editor. Infectious Disease of the Dog and Cat. 2nd ed. Philadelphia, PA: Saunders; 1998. p. 1–22.
  • Appel MJ. Pathogenesis of canine distemper. Am J Vet Res. 1969;30(7):1167–82.
  • Weisbrode SE, Krakowka S. Canine distemper virus-associated hypocalcemia. Am J Vet Res. 1979;40(1):147–9.
  • Hartmann K. Antiviral and immunomodulatory chemotherapy. In: Greene CE, editor. Infectious diseases of the dog and cat. 2013. p. 10–24.
  • De Clercq E, Cools M, Balzarini J, Snoeck R, Andrei G, Hosoya M, et al. Antiviral activities of 5-ethynyl-1-beta-D-ribofuranosylimidazole-4- carboxamide and related compounds. Antimicrob Agents Chemother. 1991;35(4):679–84.
  • Shigeta S, Mori S, Baba M, Ito M, Honzumi K, Nakamura K, et al. Antiviral activities of ribavirin, 5-ethynyl-1-beta-D-ribofuranosylimidazole-4-carboxamide, and 6’-(R)-6’-C-methylneplanocin A against several ortho- and paramyxoviruses. Antimicrob Agents Chemother. 1992;36(2):435–9.
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  • Elia G, Belloli C, Cirone F, Lucente MS, Caruso M, Martella V, et al. In vitro efficacy of ribavirin against canine distemper virus. Antivir Res. 2008;77(2):108–13.
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  • Iwasawa A, Niwano Y, Mokudai T, Kohno M. Antiviral Activity of Proanthocyanidin against Feline Calicivirus Used as a Surrogate for Noroviruses, and Coxsackievirus Used as a Representative Enteric Virus. Biocontrol Sci. 2009;14(3):107–11.
  • Takeshita M, Ishida Y, Akamatsu E, Ohmori Y, Sudoh M, Uto H, et al. Proanthocyanidin from blueberry leaves suppresses expression of subgenomic hepatitis C virus RNA. J Biol Chem. 2009;284(32):21165–76.
  • Xu XY, Xie HH, Wang YF, Wei XY. A-Type Proanthocyanidins from Lychee Seeds and Their Antioxidant and Antiviral Activities. J Agric Food Chem. 2010;58(22):11667–72.
  • Zhang XY, Li WG, Wu YH, Zheng TZ, Li W, Qu SY, et al. Proanthocyanidin from grape seeds potentiates anti-tumor activity of doxorubicin via immunomodulatory mechanism. Int Immunopharmacol. 2005;5(7–8):1247–57.
  • Gallina L, Dal Pozzo F, Galligioni V, Bombardelli E, Scagliarini A. Inhibition of viral RNA synthesis in canine distemper virus infection by proanthocyanidin A2. Antivir Res. 2011;92(3):447–52.
  • Allerton F. BSAVA Small Animal Formulary Part A: Canine and Feline. 10th ed. Allerton F, editor. Gloucester: British Small Animal Veterinary Association; 2020. 98 p.
  • Mangia SH, Moraes LF, Takahira RK, Motta RG, Franco MMJ, Megid J, et al. The side effects of ribavirin, prednisone and DMSO in dogs naturally infected by canine distemper virus. Pesqui Vet Bras. 2014;34(5):449–54.
  • Martineau A, Leray V, Lepoudere A, Blanchard G, Bensalem J, Gaudout D, et al. A mixed grape and blueberry extract is safe for dogs to consume. BMC Vet Res. 2016;12(1):162.
  • Gill M, Srinivas J, Morozov I, Smith J, Anderson C, Glover S, et al. Three-year duration of immunity for canine distemper, adenovirus, and parvovirus after vaccination with a multivalent canine vaccine. J Appl Res Vet Med. 2004;2(4):227–34.
  • Trebbien R, Chriel M, Struve T, Hjulsager CK, Larsen G, Larsen LE. Wildlife reservoirs of canine distemper virus resulted in a major outbreak in Danish farmed mink (Neovison vison). PLoS One. 2014;9(1):e85598.
  • Gemma T, Watari T, Akiyama K, Miyashita N, Shin YS, Iwatsuki K, et al. Epidemiological observations on recent outbreaks of canine distemper in Tokyo area. J Vet Med Sci. 1996;58(6):547–50.
  • Salem NY. Canine viral diarrhea: clinical, hematologic and biochemical alterations with particular reference to in-clinic rapid diagnosis. Glob Vet. 2014;13(3):302–7.
  • Ertürk N. Köpeklerde parvoviral enteritisin tedavisinde antiviral kullanımının etkinliğinin değerlendirilmesi. Sağlık Bilimleri Enstitüsü, Veteriner İç Hastalıkları Anabilim Dalı. [Tez]: Erzurum: Atatürk Üniversitesi; 2015.
  • Ogbomo H, Michaelis M, Altenbrandt B, Doerr HW, Cinatl Jr. J. A novel immunomodulatory mechanism of ribavirin in suppressing natural killer cell function. Biochem Pharmacol. 2010;79(2):188–97.
  • Lindgren C, Grogaard J. [Ribavirin treatment of children with respiratory syncytial virus bronchiolitis]. Tidsskr Nor Laegeforen. 1994;114(17):1928–9.
  • Weiss RC, Cox NR, Boudreaux MK. Toxicologic effects of ribavirin in cats. J Vet Pharmacol Ther. 1993;16(3):301–16.
  • Axthelm MK, Krakowka S. Canine distemper virus-induced thrombocytopenia. Am J Vet Res. 1987;48(8):1269–75.
  • Aydın M, Aksöz E, Korkut O, Akhan S. Farklı Pegile İnterferon-α Molekülleriyle Ribavirin Kombinasyonlarının Hematolojik Yan Etkiler Açısından Karşılaştırılması. Klimik Derg. 2014;27(3):99–102.
  • Liu YZ, Cao YG, Ye JQ, Wang WG, Song KJ, Wang XL, et al. Immunomodulatory effects of proanthocyanidin A-1 derived in vitro from Rhododendron spiciferum. Fitoterapia. 2010;81(2):108–14.
  • Huang Y, Zhao H, Cao K, Sun D, Yang Y, Liu C, et al. Radioprotective Effect of Grape Seed Proanthocyanidins In Vitro and In Vivo. Oxid Med Cell Longev. 2016;2016:5706751.
  • Kowdley K V. Hematologic side effects of interferon and ribavirin therapy. J Clin Gastroenterol. 2005;39(1 Suppl):S3-8.
  • Canonico PG, Kastello MD, Spears CT, Brown JR, Jackson EA, Jenkins DE. Effects of ribavirin on red blood cells. Toxicol Appl Pharmacol. 1984;74(2):155–62.
  • Lin C-C, Yeh L-T, Luu T, Lourenco D, Lau JYN. Pharmacokinetics and metabolism of [(14)C]ribavirin in rats and cynomolgus monkeys. Antimicrob Agents Chemother. 2003;47(4):1395–8.
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Kanin distemperde ribavirin ve proantosiyanidin'in klinik bulgular, hematolojik ve biyokimyasal parametreler ve viral saçılım üzerine etkilerinin değerlendirilmesi

Year 2023, , 125 - 135, 27.03.2023

Şükrü Değirmençay

https://doi.org/10.46810/tdfd.1244940

Abstract

Bu çalışma, canine distemper virus (CDV) ile doğal olarak enfekte olan köpeklerde ribavirin, proantosiyanidin ve ribavirin-proantosiyanidin kombinasyonunun etkilerini araştırdı. Her biri 2-6 aylık yaşta altı köpekten oluşan bir sağlıklı kontrol ve dört hasta grubu olmak üzere beş grup oluşturuldu. On gün boyunca A grubuna klasik tedavi (KT) [sıvı tedavisi ve antibiyotik], A+R grubuna KT + ribavirin, A+P grubuna KT + proantosiyanidin, A+R+P grubuna KT + ribavirin-proantosiyanidin uygulandı. T0, T3, T7 ve T10 günlerinde hematolojik ve biyokimyasal analizler ve klinik skorlama yapıldı. Bu günlerde ve tedaviden sonraki beşinci ve onuncu günlerde CDV varlığına bakıldı. Klinik skorlama A+P, A+R, A ve A+R+P gruplarının sırasıyla en iyi klinik iyileşmeyi gösterdiğini ortaya koydu. A+R grubunda toplam lökosit, nötrofil ve monositlerde düşüş gözlendi (P<0.05). CK ve CK-MB aktivitesi sadece A grubunda anlamlı olarak yüksek bulunurken (P<0.01), bu değerler sadece A+R grubunda tedavi ilerledikçe azaldı. CREA değerleri A+P ve A+R gruplarında yüksekti (P<0.01). En düşük Ca değeri A+R grubundaydı (P<0.01). Viral saçılım açısından en az CDV varlığı A+R grubunda tespit edildi. Sonuç olarak, CDV'li köpeklerde ribavirin veya proantosiyanidin kullanımı, klinik bulguların ciddiyetini azaltmaya, hayatta kalma oranını artırmaya ve viral saçılımı azaltmaya yardımcı oldu.

Keywords

antiviral ajanlar canine distemper virus proantosiyanidinler ribavirin.

References

  • Beineke A, Puff C, Seehusen F, Baumgartner W. Pathogenesis and immunopathology of systemic and nervous canine distemper. Vet Immunol Immunopathol. 2009;127(1–2):1–18.
  • Carpenter MA, Appel MJ, Roelke-Parker ME, Munson L, Hofer H, East M, et al. Genetic characterization of canine distemper virus in Serengeti carnivores. Vet Immunol Immunopathol. 1998;65(2–4):259–66.
  • Kingsbury DW. Paramyxoviridae. Intervirology. 1978;10(3):137–52.
  • Greene CE, Vandevelde M. Canine distemper. In: Greene CE, editor. Infectious diseases of the dog and cat. 4 th. St Louis,: Saunders; 2012. p. 25–42.
  • Sykes JE. Canine distemper virus infection. In: Sykes JE, editor. Canine and feline infectious diseases. 1 st. St Louis: Saunders; 2014. p. 152–65.
  • Leisewitz AL, Carter A, van Vuuren M, van Blerk L. Canine distemper infections, with special reference to South Africa, with a review of the literature. J S Afr Vet Assoc. 2001;72(3):127–36. Martella V, Elia G, Buonavoglia C. Canine distemper virus. Vet Clin North Am Small Anim Pr. 2008;38(4):787–97, vii–viii.
  • Taylor S. Encephalitis, myelitis and meningitis. In: Couto CG, Nelson RW, editors. Small Animal Internal Medicine. 4th ed. St. Louis, Missouri: Mosby Elsevier; 2009. p. 1059–62.
  • Krakowka S, Axthelm MK, Johnson GC. Canine distemper virus. In: Olsen RG, Krakowka S, Blakeslee JR, editors. Comparative Pathobiology of Viral Diseases. Boca Raton: CRC Press; 1985. p. 137–64.
  • Shell LG. Canine distemper. Compend Contin Educ Pract Vet. 1990;12(2):173–9.
  • Ezeibe MCO, Udegbunam RI. Haematology of dogs infected with canine distemper virus. Sokoto J Vet Sci. 2008;7(2):32.
  • Greene GE, Appel M. Canine Distemper Virus. In: Greene GE, editor. Infectious Disease of the Dog and Cat. 2nd ed. Philadelphia, PA: Saunders; 1998. p. 1–22.
  • Appel MJ. Pathogenesis of canine distemper. Am J Vet Res. 1969;30(7):1167–82.
  • Weisbrode SE, Krakowka S. Canine distemper virus-associated hypocalcemia. Am J Vet Res. 1979;40(1):147–9.
  • Hartmann K. Antiviral and immunomodulatory chemotherapy. In: Greene CE, editor. Infectious diseases of the dog and cat. 2013. p. 10–24.
  • De Clercq E, Cools M, Balzarini J, Snoeck R, Andrei G, Hosoya M, et al. Antiviral activities of 5-ethynyl-1-beta-D-ribofuranosylimidazole-4- carboxamide and related compounds. Antimicrob Agents Chemother. 1991;35(4):679–84.
  • Shigeta S, Mori S, Baba M, Ito M, Honzumi K, Nakamura K, et al. Antiviral activities of ribavirin, 5-ethynyl-1-beta-D-ribofuranosylimidazole-4-carboxamide, and 6’-(R)-6’-C-methylneplanocin A against several ortho- and paramyxoviruses. Antimicrob Agents Chemother. 1992;36(2):435–9.
  • del Toro-Riera M, Macaya-Ruiz A, Raspall-Chaure M, Tallada-Serra M, Pasqual-Lopez I, Roig-Quilis M. [Subacute sclerosing panencephalitis: combined treatment with interferon alpha and intraventricular ribavirin]. Rev Neurol. 2006;42(5):277–81.
  • Elia G, Belloli C, Cirone F, Lucente MS, Caruso M, Martella V, et al. In vitro efficacy of ribavirin against canine distemper virus. Antivir Res. 2008;77(2):108–13.
  • Husain SR, Cillard J, Cillard P. Hydroxyl Radical Scavenging Activity of Flavonoids. Phytochemistry. 1987;26(9):2489–91.
  • Fine AM. Oligomeric proanthocyanidin complexes: history, structure, and phytopharmaceutical applications. Altern Med Rev. 2000;5(2):144–51.
  • Cheng HY, Lin CC, Lin TC. Antiviral properties of prodelphinidin B-2 3’-O-gallate from green tea leaf. Antivir Chem Chemother. 2002;13(4):223–9.
  • Iwasawa A, Niwano Y, Mokudai T, Kohno M. Antiviral Activity of Proanthocyanidin against Feline Calicivirus Used as a Surrogate for Noroviruses, and Coxsackievirus Used as a Representative Enteric Virus. Biocontrol Sci. 2009;14(3):107–11.
  • Takeshita M, Ishida Y, Akamatsu E, Ohmori Y, Sudoh M, Uto H, et al. Proanthocyanidin from blueberry leaves suppresses expression of subgenomic hepatitis C virus RNA. J Biol Chem. 2009;284(32):21165–76.
  • Xu XY, Xie HH, Wang YF, Wei XY. A-Type Proanthocyanidins from Lychee Seeds and Their Antioxidant and Antiviral Activities. J Agric Food Chem. 2010;58(22):11667–72.
  • Zhang XY, Li WG, Wu YH, Zheng TZ, Li W, Qu SY, et al. Proanthocyanidin from grape seeds potentiates anti-tumor activity of doxorubicin via immunomodulatory mechanism. Int Immunopharmacol. 2005;5(7–8):1247–57.
  • Gallina L, Dal Pozzo F, Galligioni V, Bombardelli E, Scagliarini A. Inhibition of viral RNA synthesis in canine distemper virus infection by proanthocyanidin A2. Antivir Res. 2011;92(3):447–52.
  • Allerton F. BSAVA Small Animal Formulary Part A: Canine and Feline. 10th ed. Allerton F, editor. Gloucester: British Small Animal Veterinary Association; 2020. 98 p.
  • Mangia SH, Moraes LF, Takahira RK, Motta RG, Franco MMJ, Megid J, et al. The side effects of ribavirin, prednisone and DMSO in dogs naturally infected by canine distemper virus. Pesqui Vet Bras. 2014;34(5):449–54.
  • Martineau A, Leray V, Lepoudere A, Blanchard G, Bensalem J, Gaudout D, et al. A mixed grape and blueberry extract is safe for dogs to consume. BMC Vet Res. 2016;12(1):162.
  • Gill M, Srinivas J, Morozov I, Smith J, Anderson C, Glover S, et al. Three-year duration of immunity for canine distemper, adenovirus, and parvovirus after vaccination with a multivalent canine vaccine. J Appl Res Vet Med. 2004;2(4):227–34.
  • Trebbien R, Chriel M, Struve T, Hjulsager CK, Larsen G, Larsen LE. Wildlife reservoirs of canine distemper virus resulted in a major outbreak in Danish farmed mink (Neovison vison). PLoS One. 2014;9(1):e85598.
  • Gemma T, Watari T, Akiyama K, Miyashita N, Shin YS, Iwatsuki K, et al. Epidemiological observations on recent outbreaks of canine distemper in Tokyo area. J Vet Med Sci. 1996;58(6):547–50.
  • Salem NY. Canine viral diarrhea: clinical, hematologic and biochemical alterations with particular reference to in-clinic rapid diagnosis. Glob Vet. 2014;13(3):302–7.
  • Ertürk N. Köpeklerde parvoviral enteritisin tedavisinde antiviral kullanımının etkinliğinin değerlendirilmesi. Sağlık Bilimleri Enstitüsü, Veteriner İç Hastalıkları Anabilim Dalı. [Tez]: Erzurum: Atatürk Üniversitesi; 2015.
  • Ogbomo H, Michaelis M, Altenbrandt B, Doerr HW, Cinatl Jr. J. A novel immunomodulatory mechanism of ribavirin in suppressing natural killer cell function. Biochem Pharmacol. 2010;79(2):188–97.
  • Lindgren C, Grogaard J. [Ribavirin treatment of children with respiratory syncytial virus bronchiolitis]. Tidsskr Nor Laegeforen. 1994;114(17):1928–9.
  • Weiss RC, Cox NR, Boudreaux MK. Toxicologic effects of ribavirin in cats. J Vet Pharmacol Ther. 1993;16(3):301–16.
  • Axthelm MK, Krakowka S. Canine distemper virus-induced thrombocytopenia. Am J Vet Res. 1987;48(8):1269–75.
  • Aydın M, Aksöz E, Korkut O, Akhan S. Farklı Pegile İnterferon-α Molekülleriyle Ribavirin Kombinasyonlarının Hematolojik Yan Etkiler Açısından Karşılaştırılması. Klimik Derg. 2014;27(3):99–102.
  • Liu YZ, Cao YG, Ye JQ, Wang WG, Song KJ, Wang XL, et al. Immunomodulatory effects of proanthocyanidin A-1 derived in vitro from Rhododendron spiciferum. Fitoterapia. 2010;81(2):108–14.
  • Huang Y, Zhao H, Cao K, Sun D, Yang Y, Liu C, et al. Radioprotective Effect of Grape Seed Proanthocyanidins In Vitro and In Vivo. Oxid Med Cell Longev. 2016;2016:5706751.
  • Kowdley K V. Hematologic side effects of interferon and ribavirin therapy. J Clin Gastroenterol. 2005;39(1 Suppl):S3-8.
  • Canonico PG, Kastello MD, Spears CT, Brown JR, Jackson EA, Jenkins DE. Effects of ribavirin on red blood cells. Toxicol Appl Pharmacol. 1984;74(2):155–62.
  • Lin C-C, Yeh L-T, Luu T, Lourenco D, Lau JYN. Pharmacokinetics and metabolism of [(14)C]ribavirin in rats and cynomolgus monkeys. Antimicrob Agents Chemother. 2003;47(4):1395–8.
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There are 63 citations in total.

Details

Primary Language English
Subjects Veterinary Surgery
Journal Section Articles
Authors

Şükrü Değirmençay 0000-0002-3920-6343

Publication Date March 27, 2023
Published in Issue Year 2023

Cite

APA Değirmençay, Ş. (2023). Evaluation of the effects of ribavirin and proanthocyanidin on the clinical outcome, hematological and biochemical parameters, and viral shedding in canine distemper. Türk Doğa Ve Fen Dergisi, 12(1), 125-135. https://doi.org/10.46810/tdfd.1244940
AMA Değirmençay Ş. Evaluation of the effects of ribavirin and proanthocyanidin on the clinical outcome, hematological and biochemical parameters, and viral shedding in canine distemper. TDFD. March 2023;12(1):125-135. doi:10.46810/tdfd.1244940
Chicago Değirmençay, Şükrü. “Evaluation of the Effects of Ribavirin and Proanthocyanidin on the Clinical Outcome, Hematological and Biochemical Parameters, and Viral Shedding in Canine Distemper”. Türk Doğa Ve Fen Dergisi 12, no. 1 (March 2023): 125-35. https://doi.org/10.46810/tdfd.1244940.
EndNote Değirmençay Ş (March 1, 2023) Evaluation of the effects of ribavirin and proanthocyanidin on the clinical outcome, hematological and biochemical parameters, and viral shedding in canine distemper. Türk Doğa ve Fen Dergisi 12 1 125–135.
IEEE Ş. Değirmençay, “Evaluation of the effects of ribavirin and proanthocyanidin on the clinical outcome, hematological and biochemical parameters, and viral shedding in canine distemper”, TDFD, vol. 12, no. 1, pp. 125–135, 2023, doi: 10.46810/tdfd.1244940.
ISNAD Değirmençay, Şükrü. “Evaluation of the Effects of Ribavirin and Proanthocyanidin on the Clinical Outcome, Hematological and Biochemical Parameters, and Viral Shedding in Canine Distemper”. Türk Doğa ve Fen Dergisi 12/1 (March 2023), 125-135. https://doi.org/10.46810/tdfd.1244940.
JAMA Değirmençay Ş. Evaluation of the effects of ribavirin and proanthocyanidin on the clinical outcome, hematological and biochemical parameters, and viral shedding in canine distemper. TDFD. 2023;12:125–135.
MLA Değirmençay, Şükrü. “Evaluation of the Effects of Ribavirin and Proanthocyanidin on the Clinical Outcome, Hematological and Biochemical Parameters, and Viral Shedding in Canine Distemper”. Türk Doğa Ve Fen Dergisi, vol. 12, no. 1, 2023, pp. 125-3, doi:10.46810/tdfd.1244940.
Vancouver Değirmençay Ş. Evaluation of the effects of ribavirin and proanthocyanidin on the clinical outcome, hematological and biochemical parameters, and viral shedding in canine distemper. TDFD. 2023;12(1):125-3.

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