Ahmet Hacimuftuoglu

Comparative study on the gastroprotective potential of some antidepressants in indomethacin-induced ulcer in rats

Clinical studies have shown that anxiolytic and antidepressant drug therapy benefits patients with ulcers. Many antidepressant drugs have been shown experimentally to produce antiulcer activity in various ulcer models. This study investigated the antiulcer activities of tianeptine, trazodone, and venlafaxine on indomethacin-induced ulcers in rats; and evaluated tianeptines effects on oxidant and antioxidant parameters in rat stomach tissue. The results show that trazodone and venlafaxine did not prevent indomethacin-induced ulcers. Tianeptine, however, decreased indomethacin-induced ulcers significantly at all doses used (6, 12, and 25 mg/kg). Famotidine, an H(2) receptor blocker, showed the highest antiulcer activity. Tianeptine significantly prevented the decrease in glutathione (GSH) content that occurred in the indomethacin-only groups damaged stomach tissues. All doses of tianeptine, but especially the 25 mg/kg dose, significantly decreased catalase (CAT) activity in stomach tissue, compared to the control. All doses of tianeptine eliminated the decrease in superoxide dismutase (SOD) activity in the stomach tissue of rats given indomethacin. Although all doses of tianeptine significantly decreased the malondialdehyde (MDA) content, all doses of tianeptine, except 6 mg/kg, decreased myeloperoxidase (MPO) activities significantly compared to the control. Our results indicate that activating enzymatic and non-enzymatic antioxidant mechanisms and inhibiting some toxic oxidant mechanisms play a role in tianeptines antiulcer effect mechanism.

The effects of aqueous extract of Lavandula angustifolia flowers in glutamate-induced neurotoxicity of cerebellar granular cell culture of rat pups.

In the present study, neuroprotective effect of Lavandula angustifolia flower aqueous extract in glutamate-induced neurotoxicity in rat pups cerebellar granular cell culture was investigated. The extract at doses of 10 microg ml(-1), 100 microg ml(-1), 1 mg ml(-1) and 10 mg ml(-1) was applied to culture flasks. The extract at doses of 100 microg ml(-1) and 1 mg ml(-1) significantly blocked glutamate-induced neurotoxicity, with the most effective dose being 1 mg ml(-1). On the other hand, 10 mg ml(-1) dose of extract increased the dead cell with respect to glutamate group, despite being found insignificant statistically. As a result, L. angustifolia protected the neurons against glutamate toxicity.

A Review of Melatonin, Its Receptors and Drugs.

After a Turkish scientist took Nobel Prize due to his contributions to understand clock genes, melatonin, closely related to these genes, may begin to shine. Melatonin, a hormone secreted from the pineal gland at night, plays roles in regulating sleep-wake cycle, pubertal development and seasonal adaptation. Melatonin has antinociceptive, antidepressant, anxiolytic, antineophobic, locomotor activity-regulating, neuroprotective, anti-inflammatory, pain-modulating, blood pressure-reducing, retinal, vascular, anti-tumor and antioxidant effects. It is related with memory, ovarian physiology, and osteoblast differentiation. Pathologies associated with an increase or decrease in melatonin levels are summarized in the review. Melatonin affects by four mechanisms: 1) Binding to melatonin receptors in plasma membrane, 2) Binding to intracellular proteins such as calmoduline, 3) Binding to Orphan nuclear receptors, and 4) Antioxidant effect. Receptors associated with melatonin are as follows: 1) Melatonin receptor type 1a: MT1 (on cell membrane), 2) Melatonin receptor type 1b: MT2 (on cell membrane), 3) Melatonin receptor type 1c (found in fish, amphibians and birds), 4) Quinone reductase 2 enzyme (MT3 receptor, a detoxification enzyme), 5) RZR/RORα: Retinoid-related Orphan nuclear hormone receptor (with this receptor, melatonin binds to the transcription factors in nucleus), and 6) GPR50: X-linked Melatonin-related Orphan receptor (it is effective in binding of melatonin to MT1). Melatonin agonists such as ramelteon, agomelatine, circadin, TIK-301 and tasimelteon are introduced and side effects will be discussed. In conclusion, melatonin and related drugs is a new and promising era for medicine. Melatonin receptors and melatonin drugs will take attention with greater interest day by day in the future.

Mirtazapine protects against cisplatin-induced oxidative stress and DNA damage in the rat brain.

Cisplatin chemotherapy is associated with neurotoxicity, and oxidative stress might play an important role in the pathogenesis. Mirtazapine may be a preventative agent via its less‐known antioxidant properties. The aim of this study was to examine the potential chemoprotective effects of mirtazapine against cisplatin‐induced oxidative stress and DNA damage.

Indirect role of β2-adrenergic receptors in the mechanism of analgesic action of nonsteroidal antiinflammatory drugs

Objective:Adrenal gland hormones have been shown to have a role in the antiinflammatory effect mechanism of nonsteroidal antiinflammatory drugs. This study investigates whether the analgesic effects of indomethacin, diclofenac sodium, aspirin, and nimesulide (IDAN; upper case letters of the four drugs we used) are also related to adrenal gland hormones. Design:The analgesic effects of IDAN were studied in the carrageenan-induced inflammatory pain model using both intact and adrenalectomized rats. Paw withdrawal tests were performed in adrenalectomized rats that had been pretreated with phenoxybenzamine, propranolol, and metoprolol. Setting:This study was performed in Pharmacology and Biochemistry Laboratories of Faculty of Medicine. Patients/Subjects:A total of 306 (114 intact and 192 adrenalectomized) male Albino Wistar rats were used. Interventions:Adrernalectomy, drug administrations, pain model induction and pain threshold measurements were performed during the study. Measurements and Main Results:Although the analgesic effects of nonsteroidal antiinflammatory drugs were lost in adrenalectomized rats, they exerted significant analgesia in adrenalectomized rats that had been pretreated with prednisolone and adrenalin. All these drugs were found to decrease serum adrenalin concentration but did not change serum cortisole (corticosterone in rats) concentration. Prednisolone and adrenalin inhibited carrageenan-induced hyperalgesia in adrenalectomized rat groups pretreated with metoprolol or phenoxybenzamine, but not in rats given propranolol. Propranolol also negated the analgesic effects of IDAN in intact rats. The analgesic effects provided by either prednisolone or adrenalin could not be inhibited by the &agr;1, &agr;2, or &bgr;1 blockers but disappeared when &bgr;2 receptors were blocked. Conclusions:The analgesic effects of nonsteroidal antiinflammatory drugs appear to be related to endogenous adrenalin and cortisole. We have demonstrated that adrenalin and prednisolone play important roles in the analgesic effect mechanism of IDAN. Prednisolone and adrenalin produce analgesic effects through &bgr;2-adrenergic receptors, suggesting an indirect role for &bgr;2-adrenergic receptors in the analgesic effect mechanism of the nonsteroidal antiinflammatory drugs mentioned.

Cytotoxic and cytogenetic effects of α-copaene on rat neuron and N2a neuroblastoma cell lines

Alpha-copaene (α-COP), a tricyclic sesquiterpene, is present in several essential oils of medicinal and aromatic plants and has antioxidant and antigenotoxic features. Its cytotoxic, cytogenetic and oxidative effects have not been investigated in neuron and N2a neuroblastoma (NB) cell cultures. Therefore, we aimed to describe in vitro: (i) cytotoxic properties by 3-(4,5-dimetylthiazol-2-yl)-2,5-diphenlytetrazolium bromide test; (ii) antioxidant/oxidant activity by total antioxidant capacity (TAC) and total oxidative status (TOS) analysis; and (iii) genotoxic damage potential by single cell gel electrophoresis — of α-COP in healthy neuron and N2a-NB cell cultures for the first time. Significant (P < 0.05) decrease in cell proliferation were observed in cultured primary rat neurons starting with the concentration of 150 mg/L and in N2a-NB cells starting with 100 mg/L. In addition, 25 mg/L of α-COP treatment caused increase of TAC levels and α-COP treatments at higher doses led to increase of TOS levels in neuron N2a-NB cell cultures. Moreover, none of the tested concentrations of α-COP have shown a genotoxic effect on both cell lines. Our findings clearly demonstrate that α-COP exhibited mild cytotoxic effects on N2a-NB cell line. In conclusion, α-COP may have potential as an anticancer agent, which needs to be further studied.

Gastric anti-ulcerative and anti-inflammatory activity of metyrosine in rats

In this study, the anti-inflammatory and anti-ulcerative effects of metyrosine, a selective tyrosine hydroxylase enzyme inhibitor, were investigated in rats. For ulcer experiments, indomethacin-induced gastric ulcer tests and ethanol-induced gastric ulcer tests were used. For these experiments, rats were fasted for 24 h. Different doses of metyrosine and 25 mg/kg doses of ranitidine were administered to rats, followed by indomethacin at 25 mg/kg for the indomethacin-induced ulcer test, or 50% ethanol for the ethanol-induced test. Results have shown that at all of the doses used (50, 100 and 200 mg/kg), metyrosine had significant anti-ulcerative effects in both indomethacin and ethanol-induced ulcer tests. Metyrosine doses of 100 and 200 mg/kg (especially the 200 mg/kg dose) also inhibited carrageenan-induced paw inflammation even more effectively than indomethacin. In addition, to characterize the anti-inflammatory mechanism of metyrosine we investigated its effects on cyclooxygenase (COX) activity in inflammatory tissue (rat paw). The results showed that all doses of metyrosine significantly inhibited high COX-2 activity. The degree of COX-2 inhibition correlated with the increase in anti-inflammatory activity. In conclusion, we found that metyrosine has more anti-inflammatory effects than indomethacin and that these effects can be attributed to the selective inhibition of COX-2 enzymes by metyrosine. We also found that adrenalin levels are reduced upon metyrosine treatment, which may be the cause of the observed gastro-protective effects of this compound.

Reason for the aggravation of diseases caused by inflammation and the ineffectiveness of NSAIDs on these diseases in rainy weather

In this study, the anti-inflammatory activity of indomethacin, diclofenac, meloxicam and nimesulide were investigated on sunny and rainy days. Parallel to these experiments, the question of whether endogenous adrenaline and cortisol (corticosterone in rats) are factors that affect medicinal activity of these anti-inflammatory drugs on sunny and rainy days was examined. Our experimental results show that the drugs used produced significant anti-inflammatory effects on sunny days (76.5, 62.8, 56.9 and 64.7%, respectively) but were less effective on rainy days. On sunny days, adrenaline levels decreased by 83-86% in the groups that received indomethacin, diclofenac, meloxicam or nimesulide, compared to the control group. In contrast, there was no significant difference in corticosterone levels in any of these groups. In addition, the adrenaline and corticosterone levels of intact (versus adrenalectomized) rats decreased by 83% and 58.8%, respectively, on rainy days compared to sunny days. Indomethacin, diclofenac, meloxicam and nimesulide were found to exert anti-inflammatory effects by decreasing adrenaline levels but not affecting corticosterone levels. The anti-inflammatory effects of the tested drugs was eliminated on rainy days due to the low level of corticosterone.

Neuroprotective effect of ACE inhibitors in glutamate - induced neurotoxicity: rat neuron culture study.

AIM Glutamate is known to be neurotoxic at concentrations of 10-6M and 10-7M. Angiotensin converting enzyme (ACE) inhibitors can be assumed to be neuroprotective as they open the mitochondrial adenosine triphosphate-sensitive potassium channels by inhibiting the degradation of bradykinin. In this study, we investigated whether the ACE inhibitors captopril, ramipril and perindopril have protective effects in glutamate-induced neurotoxicity in newborn rat cerebral cortex cell cultures. MATERIAL AND METHODS Viability tests were performed among ACE inhibitors by constituting groups of control and 10-7M and 10-6M glutamate doses in newborn rat cortex cultures. RESULTS While the mean viable cell number was 0.47±0.06 in the control group, it was 0.37±0.03 in the group exposed to 10-7M glutamate (p < 0.05) and 0.37±0.01 in the group exposed to 10-6M glutamate (p < 0.05). Captopril was used at a dose of 10 μM, perindopril was used at a dose of 1 μM, and ramipril was used at a dose of 30 μM against 10-7M and 10-6M glutamate. Ramipril and perindopril reversed the toxicity against 10-6M glutamate (p < 0.05). The neuroprotective properties of captopril, perindopril and ramipril were not found to be statistically significant against 10-7M glutamate at the doses mentioned above. CONCLUSION Data obtained from this study indicate that ramipril and perindopril can prevent 10-6M glutamate-induced neurotoxicity.

Plasmapheresis is useful in phenprobamate overdose.

Although previous scientific articles claim that morbidity and mortality are low in pure skeletal muscle relaxant ingestion, this is the 10th leading cause of death recently; however, this represents only a 2.1% ratio in adult toxic exposures in the United States. We report the case of a patient with phenprobamate overdose whose neurologic and psychiatric symptoms were the dominant findings. We were unable to perform hemoperfusion because of insufficient equipment. Thus, the patient was taken to for hemodialysis for 3 hours. However, the clinical response was inadequate. Furthermore, plasmapheresis was applied using 12 U of fresh frozen plasma for the consecutive 2 days. This caused resolution of neurologic and psychiatric symptoms. The patient was released with no residual complication on the fifth day of admission. We conclude that in phenprobamate intoxication, if hemoperfusion is impossible, plasmapheresis seems to be the best modality.