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Life sciences · Review
Frontiers in Veterinary Science · September 16, 2026
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Introduction 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 in vitro evidence to distinguish established uses from extrapolated practice. Methods 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 in vivo, 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. Results 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 in vitro, 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. Discussion 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.