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Enhancement of anti-inflammatory effects of calcium channel blockers by allopurinol and dimethylsulphoxide

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Abstract

The effects of the calcium channel blockers, nifedipine, verapamil and flunarizine, and the antioxidants, allopurinol and dimethylsulphoxide, were investigated on carrageenan-induced rat paw oedema and changes in vascular permeability. Paw volume was measured by using a plethysmometer and vascular permeability was quantified by measuring the extravasated Evans blue dye 3 h after injecting the phlogistic agent. Intraperitoneal administration of nifedipine (1,2 and 4 mg/kg), verapamil (5, 10 and 20 mg/kg), flunarizine (2.5, 5 and 10 mg/kg), allopurinol (6.25, 12.5 and 25 mg/kg) and dimethylsulphoxide (20, 40 and 80 mg/kg) 30 min before carrageenan, dose dependently inhibited oedema formation and increased vascular permeability. Co-administration of the lowest doses of calcium channel blockers with the lowest doses of antioxidants produced synergistic inhibitory effects. These results indicate that both calcium influx and oxygen-derived free radicals are involved in carrageenan-induced inflammatory responses. Thus, the synergistic effects of their combination may be due to the blockade of calcium entry and reduction in the generation of oxygen-derived free radicals.

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Mobarok Ali, A.T.M., Al-Swayeh, O.A. & Al-Humayyd, M.S. Enhancement of anti-inflammatory effects of calcium channel blockers by allopurinol and dimethylsulphoxide. Inflammopharmacol 5, 397–406 (1997). https://doi.org/10.1007/s10787-997-0035-4

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  • DOI: https://doi.org/10.1007/s10787-997-0035-4

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