Magnesium Sulfate Reduces Carrageenan-Induced Rat Paw Inflammatory Edema Via Nitric Oxide Production

Abstract

Background: 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.

Keywords: NOS inhibitors; anti-edematous; anti-inflammatory; emptive therapy; magnesium; preemptive therapy.

Figure 1.

The time-response curves represent the prophylactic effect of subcutaneous magnesium sulfate (MS) administered 5 minutes before the carrageenan (Carr)-induced hind paw inflammatory edema test. Each point is the mean ± SE of differences between paw volumes in ml (dv). Compared to .9% NaCl, MS applied on its own at a dose of 5 mg/kg significantly (*P < .05) reduced edema.

Figure 2.

The time-response curves represent the therapeutic effect of subcutaneous magnesium sulfate (MS) administered 2 hours after the carrageenan (Carr)-induced hind paw inflammatory edema test. Each point is the mean ± SE of differences between paw volumes in ml (dv). Compared to .9% NaCl, MS applied on its own at a dose of 30 mg/kg significantly (*P < .05, **P < .01) reduced edema. There was a significant difference (⁺P < .05, ⁺⁺P < .01) in comparison with doses of MS of 5 and 30 mg/kg.

Figure 3.

Time-response curves for the local peripheral effect of magnesium sulfate (MS) in the carrageenan (Carr)-induced hind paw inflammatory edema test. MS was co-administered with Carr. Each point is the mean ± SE of differences between paw volumes in ml (dv). Compared to .9% NaCl, MS applied on its own at a dose of .5 mg/paw significantly (*P < .05, **P < .01) reduced edema. There was a significant difference (⁺P < .05, ⁺⁺P < .01) in comparison with the curve for the dose of MS .5 of mg/paw.

Figure 4.

Time-response curves for the effect of L-NAME (3 or 5 mg/kg) and L-arginine (L-arg. .4 mg/kg) on the effect of prophylactically administered systemic magnesium sulfate (MS 5 mg/kg) in the carrageenan (Carr)-induced hind paw inflammatory edema test. Each point is the mean ± SE of differences between paw volumes in ml (dv). L-arginine significantly decreased the effect of L-NAME on the anti-edematous effect of MS. A – *P < .05, comparison with the curve for L-NAME 3 mg/kg + MS 5 mg/kg; B – ⁺⁺P < .01, comparison with the curve for .9% NaCl; *P < .05, comparison with the curve for the combination L-NAME 5 mg/kg + MS 5 mg/kg.

Figure 5.

Time-response curves for the effect of L-NPA on the anti-edematous effect of magnesium sulfate (MS) in the carrageenan (Carr)-induced hind paw inflammatory edema test. Results are the mean ± SE of differences between paw volumes in ml (dv). L-NPA (2 mg/kg) significantly reduced the anti-edematous effect of MS 5 mg/kg. *P < .05, comparison with the curve for .9% NaCl; ⁺P < .05, comparison with the curve for MS 5 mg/kg; ^#P < .05, comparison with the combination L-NPA 2 mg/kg + MS 5 mg/kg.

Figure 6.

Time-response curves for the effect of SMT on the anti-edematous effect of magnesium sulfate (MS) in the carrageenan (Carr)-induced hind paw inflammatory edema test. Results are the mean ± SE of differences between paw volumes in mL (dv). SMT (.015 mg/kg) significantly (*P < .05) reduced the anti-edematous effect of MS 5 mg/kg.