{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T05:04:05Z","timestamp":1789535045205,"version":"build-2803163510"},"reference-count":101,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012550","name":"Nemzeti Kutat\u00e1si, Fejleszt\u00e9si \u00e9s Innovaci\u00f3s Alap","doi-asserted-by":"publisher","award":["RRF-2.3.1-21-2022-00001"],"award-info":[{"award-number":["RRF-2.3.1-21-2022-00001"]}],"id":[{"id":"10.13039\/501100012550","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      N-acetylcysteine (NAC) is used in small-animal medicine as an antidote, mucolytic, thiol donor, and cytoprotective adjunct, yet its evidentiary basis varies markedly among indications and between dogs and cats. We systematically evaluated species-specific pharmacokinetic, clinical, experimental, and\n                      <jats:italic>in vitro<\/jats:italic>\n                      evidence to distinguish established uses from extrapolated practice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A 104-record legacy evidence library was re-screened, and an update search of PubMed\/MEDLINE, Europe PMC, Crossref-resolved publisher records, Google Scholar, selected Hungarian databases and journal archives, and backward\/forward citations was completed through 1 August 2026. Eligible reports evaluated NAC in dogs or cats\n                      <jats:italic>in vivo<\/jats:italic>\n                      , or in canine- or feline-derived tissues, cells, or clinical isolates. Risk of bias was appraised with design-specific tools, and findings were synthesized narratively because interventions, models, doses, and outcomes were too heterogeneous for meta-analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Seventy-one reports were included in the qualitative synthesis. The strongest evidence supported early NAC administration for feline and canine acetaminophen toxicosis. Controlled or clinically direct evidence also supported redox restoration in hospitalized dogs, adjunctive treatment of canine parvoviral enteritis, short-course intravenous treatment in cats with acute-on-chronic kidney disease and selected topical ophthalmic applications. Antibacterial and antibiofilm activity against canine otitis and infectious-keratitis pathogens was reproducible\n                      <jats:italic>in vitro<\/jats:italic>\n                      , and a small clinical study supported multicomponent topical therapy for superficial pyoderma; however, NAC-specific effects and antimicrobial interactions remained formulation dependent. Experimental cardiopulmonary, renal, hepatic, and diabetic-organ-protection studies yielded biologically coherent but clinically immature signals. Conversely, perioperative neuroprotection, doxorubicin cardioprotection, and nebulized treatment of feline asthma were neutral or unfavorable. Conventional aqueous NAC pharmacokinetics remain undefined in dogs, and many widely quoted dosing schedules originate from expert synthesis rather than dose-ranging trials.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>NAC is therefore best regarded as an evidence-supported antidote and a context-dependent adjunct, not a generic antioxidant therapy. Future studies should prioritize canine pharmacokinetics, standardized formulations, clinically meaningful outcomes, and prospective validation of topical antimicrobial and renal indications.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fvets.2026.1959626","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T04:29:09Z","timestamp":1789532949000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["From antidote to multimodal adjunct: a systematic review of N-acetylcysteine in dogs and cats"],"prefix":"10.3389","volume":"13","author":[{"given":"Zsombor Tam\u00e1s","family":"T\u00f3th","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, University of Veterinary Medicine Budapest","place":["Budapest, Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"No\u00e9mi Katalin","family":"Tarpataki","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Veterinary Medicine Budapest","place":["Budapest, Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melinda","family":"Nemes-Ter\u00e9nyi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Veterinary Medicine Budapest","place":["Budapest, Hungary"]},{"name":"National Laboratory of Infectious Animal Diseases, Antimicrobial Resistance, Veterinary Public Health and Food Chain Safety, University of Veterinary Medicine Budapest","place":["Budapest, Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1kos","family":"Jerzsele","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Veterinary Medicine Budapest","place":["Budapest, Hungary"]},{"name":"National Laboratory of Infectious Animal Diseases, Antimicrobial Resistance, Veterinary Public Health and Food Chain Safety, University of Veterinary Medicine Budapest","place":["Budapest, Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1d\u00e1m","family":"Kerek","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Veterinary Medicine Budapest","place":["Budapest, Hungary"]},{"name":"National Laboratory of Infectious Animal Diseases, Antimicrobial Resistance, Veterinary Public Health and Food Chain Safety, University of Veterinary Medicine Budapest","place":["Budapest, Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1080\/10715762.2018.1468564","article-title":"N-Acetylcysteine as an antioxidant and disulphide breaking agent: the reasons why","volume":"52","author":"Aldini","year":"2018","journal-title":"Free Radic Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1016\/0891-5849(89)90066-X","article-title":"The antioxidant action of N-acetylcysteine: its reaction with hydrogen peroxide, hydroxyl radical, superoxide, and hypochlorous acid","volume":"6","author":"Aruoma","year":"1989","journal-title":"Free Radic Biol Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.mam.2008.05.005","article-title":"Regulation of glutathione synthesis","volume":"30","author":"Lu","year":"2009","journal-title":"Mol Aspects Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"4117","DOI":"10.1016\/j.bbagen.2013.04.016","article-title":"The chemistry and biological activities of N-acetylcysteine","volume":"1830","author":"Samuni","year":"2013","journal-title":"Biochim Biophys Acta."},{"key":"B5","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1007\/s000180300001","article-title":"Molecular mechanisms of N-acetylcysteine actions","volume":"60","author":"Zafarullah","year":"2003","journal-title":"Cell Mol Life Sci."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1867","DOI":"10.3390\/antiox12101867","article-title":"N-acetylcysteine and its immunomodulatory properties in humans and domesticated animals","volume":"12","author":"Tieu","year":"2023","journal-title":"Antioxidants."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.1016\/S0006-2952(97)00072-5","article-title":"Molecular basis for deficient acetaminophen glucuronidation in cats. 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