Effect of Ozonized saline solution on oxidative stress in cats with Feline Infectious Peritonitis

• Rahşan Koc Akpinar Republic of Türkiye, Ministry of Agriculture and Forestry, Samsun Veterinary Control Institute, 55200, Samsun, Türkiye. https://orcid.org/0000-0003-0075-9247
• Büşra Sahin Ondokuz Mayıs University, Faculty of Veterınary, Department of Biochemistry, 55100, Samsun, Türkiye. https://orcid.org/0000-0002-5245-478X
• Medine Özlek Ondokuz Mayıs University, Faculty of Veterınary, Department of İnternal Medicine, 55100, Samsun, Türkiye. https://orcid.org/0009-0003-5139-6498
• Sercan Sever Ondokuz Mayıs University, Faculty of Veterınary, Department of İnternal Medicine, 55100, Samsun, Türkiye. https://orcid.org/0009-0005-6244-1236
• Yucel Meral Ondokuz Mayıs University, Faculty of Veterınary, Department of İnternal Medicine, 55100, Samsun, Türkiye. https://orcid.org/0000-0001-9099-5061
• Duygu Dalgın Ondokuz Mayıs University, Faculty of Veterınary, Department of İnternal Medicine, 55100, Samsun, Türkiye. https://orcid.org/0000-0001-5253-5232
• Sena Cenesiz Ondokuz Mayıs University, Faculty of Veterınary, Department of Biochemistry, 55100, Samsun, Türkiye. https://orcid.org/0000-0002-3544-503X

DOI: https://doi.org/10.52973/rcfcv-e362876

Keywords: Cat, Feline infectious peritonitis, oxidative stress, ozone, reverse transcription-polymerase chain reaction, Türkiye

Abstract

Feline infectious peritonitis is a viral disease in cats characterized by systemic involvement and a frequently fatal outcome. Diagnosis is established through a comprehensive assessment of clinical signs and laboratory findings. The aim of this study was to evaluate the efficacy of a single intravenous administration of 100 mL of 0.9 % isotonic sodium chloride solution, ozonated at a concentration of 5 μg/mL for 5 minutes using the Vetozone Medical Ozone Device, on oxidative stress parameters and survival time. In this context, oxidative stress markers were compared  before  and  after  treatment to provide scientific data on the potential therapeutic effects of ozonated saline in veterinary medicine. The study was conducted on a sample of 10 domestic cats diagnosed with Feline infectious peritonitis, all of which were monitored for a follow-up period of 6 months to assess clinical progression and survival. In the study conducted on cats diagnosed with Feline infectious peritonitis, administration of ozonated saline resulted in increased total antioxidant capacity and native thiol levels, accompanied by decreases in total oxidant capacity, oxidative stress index, and disulfide levels at the 1-hour mark. Although these changes were not statistically significant (P> 0.05), the findings suggest that ozone exerts a regulatory effect on oxidative stress and helps restore the thiol–disulfide balance toward an antioxidant state. In addition, the treatment markedly improved clinical signs, reduced oxidative stress markers, and achieved a 100 % survival rate in the treated cats. These results indicate that ozonated saline solution, by reducing free radical–induced cellular damage in cats with Feline infectious peritonitis, has the potential to be used as a supportive (adjuvant) approach rather than as a directly curative therapeutic agent. Nevertheless, larger controlled clinical studies with extended follow-up periods are required to validate these effects and to standardize the therapeutic protocol.

References

Pedersen NC. A review of feline infectious peritonitis virus infection: 1963–2008. J. Feline Med. Surg. [Internet]. 2009; 11(4):225–258. doi: https://doi.org/fjg9k5 DOI: https://doi.org/10.1016/j.jfms.2008.09.008

Simons FA, Vennema H, Rofina JE, Pol JM, Horzinek MC, Rottier PJ, Egberink HF. A mRNA PCR for the diagnosis of feline infectious peritonitis. J. Virol. Methods. [Internet]. 2005; 124(1-2):111-116. doi: https://doi.org/bspjb4 DOI: https://doi.org/10.1016/j.jviromet.2004.11.012

Tanaka Y, Sato Y, Takahashi D, Matsumoto H, Sasaki T. Treatment of a case of feline infectious peritonitis with cyclosporin A. Vet. Rec. Case Rep. [Internet]. 2015; 3(1):e000134. doi: https://doi.org/qsv2 DOI: https://doi.org/10.1136/vetreccr-2014-000134

Kennedy MA. Feline infectious peritonitis: update on pathogenesis, diagnostics, and treatment. Vet. Clin. N.Am. Small Anim. Pract. [Internet]. 2020; 50(5):1001- 1011. doi: https://doi.org/gn6d4riio DOI: https://doi.org/10.1016/j.cvsm.2020.05.002

Kipar A, Bellmann S, Gunn-Moore DA, Leukert W, Köhler K, Menger S, Reinacher M. Histopathological alterations of lymphatic tissues in cats without feline infectious peritonitis after long-term exposure to FIP virus. Vet. Microbiol. [Internet]. 1999; 69(1-2):131-137. doi: https://doi.org/b2xttb DOI: https://doi.org/10.1016/S0378-1135(99)00101-7

Hartmann K. Feline infectious peritonitis. Vet. Clin. N. Am. Small Anim. Pract. [Internet]. 2005; 35(1):39-79. doi: https://doi.org/cn39h4 DOI: https://doi.org/10.1016/j.cvsm.2004.10.011

Dye C, Siddell SG. Genomic RNA sequence of feline coronavirus strain FCoV C1Je. J. Feline Med. Surg. [Internet]. 2007; 9(3):202-213. doi: https://doi.org/btswzs DOI: https://doi.org/10.1016/j.jfms.2006.12.002

Shiba N, Maeda K, Kato H, Mochizuki M, Iwata H. Differentiation of feline coronavirus type I and II infections by virus neutralization test. Vet. Microbiol. [Internet]. 2007; 124(3-4):348-352. doi: https://doi.org/c9qz4h DOI: https://doi.org/10.1016/j.vetmic.2007.04.031

Addie D, Belák S, Boucraut-Baralon C, Egberink H, Frymus T, Gruffydd-Jones T, Hartmann K, Hosie MJ, Lloret A, Lutz H, Marsilio F, Pennisi MG, Radford AD, Thiry E, Truyen U, Horzinek MC. Feline infectious peritonitis. ABCD guidelines on prevention and management. J. Feline Med. Surg. [Internet]. 2009; 11(7):594-604. doi: https://doi.org/fsrxcs DOI: https://doi.org/10.1016/j.jfms.2009.05.008

Thayer V, Gogolski S, Felten S, Hartmann K, Kennedy M, Olah GA. 2022 AAFP/EveryCat feline infectious peritonitis diagnosis guidelines. J. Feline Med. Surg. [Internet]. 2022; 24(9):905-933. doi: https://doi.org/qswn DOI: https://doi.org/10.1177/1098612X221118761

Tsai HY, Chueh LL, Lin CN, Su BL. Clinicopathological findings and disease staging of feline infectious peritonitis: 51 cases from 2003 to 2009 in Taiwan. J. Feline Med. Surg. [Internet]. 2011; 13(2):74-80. doi. https://doi.org/btp5w4 DOI: https://doi.org/10.1016/j.jfms.2010.09.014

Moyadee W, Sunpongsri S, Choowongkomon K, Roytrakul S, Rattanasrisomporn A, Tansakul N, Rattanasrisomporn J. Feline infectious peritonitis: A comprehensive evaluation of clinical manifestations, laboratory diagnosis, and therapeutic approaches. J. Adv. Vet. Anim. Res. [Internet]. 2024; 11(1):19-26. doi: https://doi.org/qswp DOI: https://doi.org/10.5455/javar.2024.k742

Norris JM, Bosward KL, White JD, Baral RM, Catt MJ, Malik R. Clinicopathological findings associated with feline infectious peritonitis in Sydney, Australia: 42 cases (1990–2002). Aust. Vet. J. [Internet]. 2005; 83(11):666-673. doi: https://doi.org/d3bqhv DOI: https://doi.org/10.1111/j.1751-0813.2005.tb13044.x

Hartmann K, Hein J. Bartonellosis. In:Hartmann K, Hein J, eds. Infektionskrankheiten der Katze. 1st edition. Hannover, Deutschland: Schlütersche Verlagsgesellschaft mbH & Co KG.: 2008; 182–188.

Hartmann K, Binder C, Hirschberger J, Cole D, Reinacher M, Schroo S, Frost J, Egberink H, Lutz H, Hermanns W. Comparison of different tests to diagnose feline infectious peritonitis. J. Vet. Intern. Med. [Internet]. 2003; 17(6):781-790. doi: https://doi.org/bgt55z DOI: https://doi.org/10.1111/j.1939-1676.2003.tb02515.x

Marteles D, Lebrero ME, Fernández A, Ortín A, González A, Morell C, Villanueva MJ, Schäfer I, Quílez P, Verde M, Gómez A, Villanueva-Saz S. Impact of single versus multiple infection on serum protein fractions in cats. Vet. Res. Commun. [Internet]. 2025; 49(3):158. doi: https://doi.org/qsw5 DOI: https://doi.org/10.1007/s11259-025-10724-w

Nohl H, Gille L, Staniek K. Intracellular generation of reactive oxygen species by mitochondria. Biochem. Pharmacol. [Internet]. 2005; 69(5):719-723. doi: https://doi.org/c3fcf5 DOI: https://doi.org/10.1016/j.bcp.2004.12.002

Decaro N, Martella V, Saif LJ, Buonavoglia C. COVID-19 from veterinary medicine and one health perspectives: What animal coronaviruses have taught us. Res. Vet. Sci. [Internet]. 2020; 131:21-23. doi: https://doi.org/ggr26w DOI: https://doi.org/10.1016/j.rvsc.2020.04.009

Bocci V. Ozone: A New Medical Drug. 1st ed. Dordrecht: Springer Netherlands; 2005.

Kim HS, Noh SU, Han YW, Kim KM, Kang H, Kim HO, Park YM. Therapeutic effects of topical application of ozone on acute cutaneous wound healing. J. Korean Med. Sci. [Internet]. 2009; 24(3):368-374. doi: https://doi.org/cn8c8r DOI: https://doi.org/10.3346/jkms.2009.24.3.368

Travagli V, Zanardi I, Valacchi G, Bocci V. Ozone and ozonated oils in skin diseases: a review. Mediators Inflamm. [Internet]. 2010; 2010(1):610418. doi: https://doi.org/d88b4z DOI: https://doi.org/10.1155/2010/610418

Gao YY, Wang Q, Liang XY, Zhang S, Bao D, Zhao H, Li SB, Wang K, Hu GX, Gao FS. An updated review of feline coronavirus: Mind the two biotypes. Virus Res. 2023; 326:199059. doi: https://doi.org/grq9dr DOI: https://doi.org/10.1016/j.virusres.2023.199059

Riemer F, Kuehner KA, Ritz S, Sauter-Louis C, Hartmann K. Clinical and laboratory features of cats with feline infectious peritonitis–a retrospective study of 231confirmed cases (2000–2010). J. Feline Med. Surg. [Internet]. 2015; 18(4):348-356. doi: https://doi.org/f8g6hh DOI: https://doi.org/10.1177/1098612X15586209

Sparkes AH, Hopper CD, Millard WG, Gruffydd-Jones TJ, Harbour DA. Feline immunodeficiency virus infection clinicopathologic findings in 90 naturally occurring cases.J. Vet. Intern. Med. [Internet]. 1993; 7(2):85-90. doi: https://doi.org/dz4w52

Jeffery U, Deitz K, Hostetter S. Positive predictive value of albumin: globulin ratio for feline infectious peritonitis in a mid-western referral hospital population. J. Feline Med. Surg. [Internet]. 2012; 14(12):903-905. doi: https://doi.org/f4dz55

Sparkes AH, Hopper CD, Millard WG, Gruffydd-Jones TJ, Harbour DA. Feline immunodeficiency virus infection clinicopathologic findings in 90 naturally occurring cases. J. Vet. Intern. Med. [Internet]. 1993; 7(2):85-90. doi: https://doi.org/dz4w52 DOI: https://doi.org/10.1111/j.1939-1676.1993.tb03174.x

Jeffery U, Deitz K, Hostetter S. Positive predictive value of albumin: globulin ratio for feline infectious peritonitis in a mid-western referral hospital population. J. Feline Med. Surg. [Internet]. 2012; 14(12):903-905. doi: https://doi.org/f4dz55 DOI: https://doi.org/10.1177/1098612X12454862

Erel O, Neselioglu S. A novel and automated assay for thiol/disulphide homeostasis. Clin. Biochem. [Internet]. 2014; 47(18):326-332. doi: https://doi.org/f6r6dk DOI: https://doi.org/10.1016/j.clinbiochem.2014.09.026

Webb C, Lehman T, McCord K, Avery P, Dow S. Oxidative stress during acute FIV infection in cats. Vet. Immunol. Immunopathol. [Internet]. 2008; 122(1-2):16-24. doi: https://doi.org/b6gcmt DOI: https://doi.org/10.1016/j.vetimm.2007.11.004

Webb C, Bedwell C, Guth A, Avery P, Dow S. Use of flow cytometry and monochlorobimane to quantitate intracellular glutathione concentrations in feline leukocytes. Vet. Immunol. Immunopathol. [Internet]. 2006; 112(3-4):129-140. doi: https://doi.org/frpk5b DOI: https://doi.org/10.1016/j.vetimm.2006.02.009

Treitinger A, Spada C, Verdi JC Miranda AF, Oliveira OV, Silveira MV, Moriel P, Abdalla DS. Decreased antioxidant defence in individuals infected by the human immunodeficiency virus. Eur. J. Clin. Investig. [Internet]. 2000; 30(5):454-459. doi: https://doi.org/csqrcf DOI: https://doi.org/10.1046/j.1365-2362.2000.00642.x

Flohé L. Looking back at the early stages of redox biology. Antioxidants. [Internet]. 2020; 9(12):1254. doi: https://doi.org/gnw8km DOI: https://doi.org/10.3390/antiox9121254

Suresh DR, Annam V, Pratibha K, Prasad BM. Total antioxidant capacity–a novel early bio-chemical marker of oxidative stress in HIV infected individuals. J. Biomed. Sci. [Internet]. 2009; 16(1):61. doi: https://doi.org/bzfxbb DOI: https://doi.org/10.1186/1423-0127-16-61

Li C, Liu Q, Kong F, Guo D, Zhai J, Su M, Sun D. Circulation and genetic diversity of Feline coronavirus type I and II from clinically healthy and FIP-suspected cats in China. Transbound. Emerg. Dis. [Internet]. 2019; 66(2):763-775. doi: https://doi.org/qsx4 DOI: https://doi.org/10.1111/tbed.13081

Sase O, Iwami T, Sasaki T, Sano T. GS-441524 and molnupiravir are similarly effective for the treatment of cats with feline infectious peritonitis. Front. Vet. Sci. [Internet]. 2024; 11:1422408. doi: https://doi.org/qsx5 DOI: https://doi.org/10.3389/fvets.2024.1422408

Hu T, Zhang H, Zhang X, Hong X, Zhang T. Prevalence and risk factors associated with feline infectious peritonitis (FIP) in Mainland China between 2008 and 2023: A systematic review and meta-analysis. Animals. [Internet]. 2024; 14(8):1220. doi: https://doi.org/g9h6sn DOI: https://doi.org/10.3390/ani14081220

Roy M, Jacque N, Novicoff W, Li E, Negash R, Evans, SJ. Unlicensed Molnupiravir is an Effective Rescue Treatment Following Failure of Unlicensed GS-441524-like Therapy for Cats with Suspected Feline Infectious Peritonitis. Pathogens. [Internet]. 2022; 11(10):1209. doi: https://doi.org/qsx7 DOI: https://doi.org/10.3390/pathogens11101209

Negash R, Li E, Jacque N, Novicoff W, Evans SJ. Owner experience and veterinary involvement with unlicensed GS-441524 treatment of feline infectious peritonitis: A prospective cohort study. Front. Vet. Sci. [Internet]. 2024; 11:1377207. doi: https://doi.org/qsx8 DOI: https://doi.org/10.3389/fvets.2024.1377207

Green J, Syme H, Tayler S. Thirty-two cats with effusive or non-effusive feline infectious peritonitis treated with a combination of remdesivir and GS-441524. J. Vet. Intern. Med. [Internet]. 2023; 37(5):1784-1793. doi: https://doi.org/g7mvt4 DOI: https://doi.org/10.1111/jvim.16804

Coggins SJ, Norris JM, Malik R, Govendir M, Hall EJ, Kimble B, Thompson MF. Outcomes of treatment of cats with feline infectious peritonitis using parenterally administered remdesivir, with or without transition to orally administered GS-441524. J. Vet. Intern. Med. [Internet]. 2023; 37(5):1772-1783. doi: https://doi.org/qsx9 DOI: https://doi.org/10.1111/jvim.16803

Anwer AZ, Abdulkader MS, Massieh ESA. Outcomes of Treatment of Cats with Effusive Feline Infectious Peritonitis Using Parenterally Administered Remdesivir with Two Different Maintenance Dose Concentrations. Kafkas Univ. Vet. Fak. Derg. [Internet]. 2025; 31(2):259-266. doi: https://doi.org/qszc DOI: https://doi.org/10.9775/kvfd.2024.33487

Ritz S, Egberink H, Hartmann K. Effect of feline interferon- omega on the survival time and quality of life of cats with feline infectious peritonitis. J. Vet. Intern. Med. [Internet]. 2007; 21(6):1193-1197. doi: https://doi.org/c8sfrz DOI: https://doi.org/10.1111/j.1939-1676.2007.tb01937.x

Fischer Y, Ritz S, Weber K, Sauter-Louis C, Hartmann K. Randomized, placebo controlled study of the effect of propentofylline on survival time and quality of life of cats with feline infectious peritonitis. J. Vet. Intern. Med. [Internet]. 2011; 25(6):1270-1276. doi: https://doi.org/bg49h8 DOI: https://doi.org/10.1111/j.1939-1676.2011.00806.x

Ishida T, Shibanai A, Tanaka S, Uchida K, Mochizuki M. Use of recombinant feline interferon and glucocorticoid in the treatment of feline infectious peritonitis. J. Feline Med. Surg. [Internet]. 2004; 6(2):107-109. doi: https://doi.org/dzfk9q DOI: https://doi.org/10.1016/j.jfms.2003.08.011