Effect of zinc on the anti-inflammatory and ulcerogenic activities of indometacin and diclofenac.
In the present study, the potential anti-inflammatory activity of zinc sulfate (zinc) has been examined in rats with acute and chronic inflammation. Additionally, we studied the effect of the concurrent administration of zinc on the anti-inflammatory activity of indometacin and diclofenac and their gastric side effects. Oral or subcutaneous administration of zinc (25 and 15 mg/kg, respectively) significantly reduced carrageenan-induced paw edema. Subcutaneous co-administration of zinc (15 mg/kg) and indometacin (5 mg/kg) or diclofenac (10 mg/kg) resulted in a further reduction in paw edema which was more than either that produced by either agent alone. However, after oral co-administration of zinc and diclofenac the reduction in paw edema was not significantly different from that produced by either zinc or diclofenac alone. In rats with chronic inflammation, the administration of zinc (5 mg/kg s.c. for 7 days) proved as effective as either indometacin (3 mg/kg) or diclofenac (5 mg/kg). Co-administration of zinc with indometacin or diclofenac did not affect the level of activity of either drug. Co-administration of zinc did not affect the ulcerogenic effect of indometacin expressed as the ulcer index. In contrast to indometacin, administration of zinc markedly reduced the ulcerative action of diclofenac. In conclusion, zinc supplementation may contribute significantly to the treatment of inflammation. The combination of zinc with other anti-inflammatory drugs may provide beneficial additive effects and reduce their gastric hazards, particularly with diclofenac.
Abou-Mohamed
G
G
Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta 30912, USA.
el-Kashef
H A
HA
Salem
H A
HA
Elmazar
M M
MM
D000704:Analysis of Variance; D000818:Animals; D004008:Diclofenac / Q000494:pharmacology* / Q000633:toxicity; D004347:Drug Interactions; D007213:Indomethacin / Q000494:pharmacology* / Q000633:toxicity; D008297:Male; D051381:Rats; D013276:Stomach Ulcer / Q000139:chemically induced*; D015032:Zinc / Q000494:pharmacology*
D004008:Diclofenac; D015032:Zinc; D007213:Indomethacin