Abstract
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.
Highlights
Since the ancient times, medicines derived from willow trees and other salicylate-rich plants have been used for relieving pain and reducing fever
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 non-steroidal anti-inflammatory drugs (NSAIDs) complexes with zinc and mixtures with zinc hydroaspartate (ZHA) alleviated ulcerations caused by parent NSAIDs; 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
Summary
Medicines derived from willow trees and other salicylate-rich plants have been used for relieving pain and reducing fever It was not until the isolation of salicin in 1828 and the subsequent development of the drug aspirin in 1899 that pharmacologists’ interest in non-steroidal anti-inflammatory drugs (NSAIDs) was awakened. The primary mechanism of action of NSAIDs is the inhibition of cyclooxygenase (COX) enzymes, leading to reduced prostaglandin biosynthesis, which determines their versatile effectiveness as analgesics, antipyretics, and anti-inflammatory agents (Capone et al 2007). This mechanism largely contributes to the gastrointestinal (GI) toxicity of NSAIDs (Watanabe et al 2002; Wallace 2008).
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