Srebro, Dragana (55601466500)Dragana (55601466500)SrebroDožić, Branko (6507142704)Branko (6507142704)DožićSavić Vujović, Katarina (57217857650)Katarina (57217857650)Savić VujovićMedić Brkić, Branislava (56029608400)Branislava (56029608400)Medić BrkićVučković, Sonja (7003869333)Sonja (7003869333)Vučković2025-06-122025-06-122023https://doi.org/10.1177/15593258231155788https://www.scopus.com/inward/record.uri?eid=2-s2.0-85147442717&doi=10.1177%2f15593258231155788&partnerID=40&md5=93bdc69b8691567a80fdc424a86d6e82https://remedy.med.bg.ac.rs/handle/123456789/3128Background: Magnesium is an antagonist of the N-methyl-D-aspartate receptor. This study aimed to investigate the anti-edematous effect of magnesium sulfate (MS) in different protocols of use and the possible mechanism of its action. Methods: In a rat model of carrageenan-induced paw inflammation, the anti-edematous activity of MS was assessed with a plethysmometer. The effects of the nonselective inhibitor (L-NAME), selective inhibitor of neuronal (L-NPA) and inducible (SMT) nitric oxide synthase on the effects of MS were evaluated. Results: MS administered systemically before or after inflammation reduced edema by 30% (5 mg/kg, P <.05) and 55% (30 mg/kg, P <.05). MS administered locally (.5 mg/paw, P <.05) significantly prevented the development of inflammatory edema by 60%. L-NAME, intraperitoneally administered before MS, potentiated (5 mg/kg, P <.05) or reduced (3 mg/kg, P <.05), while in the highest tested dose L-NPA (2 mg/kg, P <.01) and SMT (.015 mg/kg, P <.01) reduced the anti-edematous effect of MS. Conclusions: Magnesium is a more effective anti-edematous drug in therapy than for preventing inflammatory edema. The effect of MS is achieved after systemic and local peripheral administration and when MS is administered as a single drug in a single dose. This effect is mediated at least in part via the production of nitric oxide. © The Author(s) 2023.anti-edematousanti-inflammatoryemptive therapymagnesiumNOS inhibitorspreemptive therapy