36 research outputs found
Evaluation of anti-inflammatory and ulcerogenic potential of zinc-ibuprofen and zinc-naproxen complexes in rats
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
Berberine produces antidepressant-like effects in ovariectomized mice
Berberine has been reports to have antidepressant-like effects. However, it is seldom known whether berberine produces antidepressant-like effects in ovariectomized mice, which exhibit depressive-like responses. To examine the antidepressant-like effects of berberine in ovariectomized mice, behavioral tests were conducted, including the forced swimming test and the open field test. To elucidate the mechanisms, levels of BDNF, phosphorylated CREB and phosphorylated eEF2 were analyzed by western blotting, and c-Fos induction was examined by immunohistochemistry. In the forced swimming test, berberine decreased the immobility time in a dose-dependent manner, reversing the depressive-like effect observed in ovariectomized mice, and this effect was blocked by the 5-HT2 antagonist ketanserin. In addition, western blotting indicated that BDNF and peEF2 in the hippocampus, but not pCREB/CREB in the frontal cortex, were affected by berberine treatment. Furthermore, immunohistochemistry demonstrated that the reduction in c-Fos induced by ovariectomy were greater after berberine treatment. Ketanserin also antagonized the effect of berberine on the c-Fos expression. Our findings suggest that berberine exerts antidepressant-like effects in ovariectomized mice, and 5-HT2 receptor activation may be partially related to the antidepressant-like effects of the berberine by BDNF-CREB and eEF2 pathways
Zinc in the glutamatergic theory of depression
Depression is a serious psychiatric illness that affects millions of people worldwide. Weeks of antidepressant therapy are required to relieve depressive symptoms, and new drugs are still being extensively researched. The latest studies have shown that in depression, there is an imbalance between the main excitatory (glutamatergic) and inhibitory (GABAergic) systems. Administration of antagonists of the glutamatergic system, including zinc, has shown an antidepressant effect in preclinical as well as clinical studies. Zinc inhibits the NMDA receptor via its binding site located on one of its subunits. This is thought to be the main mechanism explaining the antidepressant properties of zinc. In the present review, a link between zinc and the glutamatergic system is discussed in the context of depressive disorder
Up-regulation of the GPR39 Zn(2+)-sensing receptor and CREB/BDNF/TrkB pathway after chronic but not acute antidepressant treatment in the frontal cortex of zinc-deficient mice
Zinc deficiency induces behavioral alterations in the tail suspension test in mice : effect of antidepressants
Background: Recently, experimental zinc deficiency has been correlated with depression-like alterations in rodents. Methods: In the first part of present study, the time course of zinc deficient diet induced alterations in the tail suspension test (TST) in mice was investigated. In the second part, the effect of imipramine and escitalopram in control and zinc-deprived for 3 weeks mice was examined in the TST. Results: A4- and 10-week administration of a Zn-deficient diet enhanced the immobility time in the TST (by 20 % and 57 %, respectively). By contrast, a 2-week period of a zinc deficient diet effected the reduction (by 24%) of the immobility time. Moreover, a 2- and 4-week (but not 10-week) of a Zn-deficient diet resulted in the reduction of the body weight (by 37 % and 18 %, respectively). These results indicate the developing response to zinc deficiency induced by a zinc-deficient diet. The antidepressant-like effect (reduction in the immobility time) of both drugs was significantly reduced in zinc-deprived mice, which suggests treatment-resistance induced by zinc deprivation. Conclusion: Zinc deprivation induces "pro-depressive" behavior and alters antidepressant efficacy