Supplementary file 1_From antidote to multimodal adjunct: a systematic review of N-acetylcysteine in dogs and cats.docx

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.</p>Discussion<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.</p>