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.