Because of numerous indications and high availability, non-steroidal anti-inflammatory drugs (
NSAIDs) are among the most commonly prescribed and used medicines in the world. However, long-term
therapy with and improper use of
NSAIDs may lead to gastrointestinal damage. Therefore, improving the therapeutic index of the existing drugs has become a priority over the past decades. Considerable attention in the field has been concentrated on
metal complexes of non-steroidal anti-inflammatory drugs. The aim of this study is to evaluate the effect of complexation with
zinc on the anti-inflammatory and ulcerogenic effects of
ibuprofen and
naproxen after single and triple intragastric administration to rats. The anti-inflammatory effect was assessed in
carrageenan-induced inflammatory
edema in the hind paw of male albino Wistar rats. The mucosal lesions were inspected and evaluated for gross pathology. Single administration of both the investigated complexes, namely
zinc-
ibuprofen and
zinc-
naproxen (20 mg/kg equivalent to
ibuprofen and
naproxen, respectively) and their parent drugs and physical mixtures with
zinc hydroaspartate (ZHA doses: 16.05 and 14.37 mg/kg), caused a significant reduction of the
edema after the same time from the
carrageenan injection in comparison to the control groups. However, no statistically significant differences between the investigated drugs were observed after their single administration. The mean ulceration score for the mixture of
ibuprofen and ZHA was statistically lower than the mean score achieved in rats
after treatment with
ibuprofen alone. On the other hand, triple intragastric administration of the ZHA-
ibuprofen and ZHA-
naproxen combination showed substantial enhancement of the anti-inflammatory activity against control groups, as well as against the parent
NSAIDs. The most potent anti-inflammatory activity was demonstrated after 2 h from the
carrageenan injection in animals receiving ZHA together with
naproxen. The
edema growth was reduced in these animals by 80.9% as compared to the control group. This result was significantly higher than the results achieved in animals receiving
zinc-
naproxen (50.2%) or
naproxen alone (47.9%). Both
NSAID complexes with
zinc and mixtures with ZHA alleviated ulcerations caused by parent
NSAIDs; however, the mixtures of both
ibuprofen and
naproxen with ZHA after triple administration were the least damaging. In view of the above results,
zinc supplementation during
NSAID therapy may have a beneficial effect on
ulcer prevention and healing by reducing the effective dose of the parent
drug and increasing its potency.