Basar Sirmagul

Some Pyridazinone and Phthalazinone Derivatives and Their Vasodilator Activities

In this study, 6-[(4-arylidene-2-phenyl-5-oxoimidazolin-1-yl)phenyl]-4,5-dihydro-3(2H)-pyridazinone and 4-[(4-arylidene-2-phenyl-5-oxoimidazolin-1-yl)phenyl]-1(2H)-phthalazinone derivatives were synthesized by reacting 6-(4-aminophenyl)-4,5-dihydro-3(2H)-pyridazinone or 4-(4-aminophenyl)-1(2H)-phthalazinone compound with different 4-arylidene-2-phenyl-5(4H)-oxazolone derivatives. The vasodilator activities of the compounds were examined bothin vitro andin vivo. Some pyridazinone derivatives showed appreciable activity.

Effects of verapamil and nifedipine on different parameters in lipopolysaccharide-induced septic shock

Septic shock has a high mortality rate due to the hypotension and circulatory disorder that occurs during its pathogenesis. Recently, humoral factors such as cytokines and nitric oxide became important in the complex pathophysiology of septic shock because there is a close relationship between the determined levels of these humoral factors and the responses to the therapy and survival periods. Verapamil and nifedipine are calcium channel blockers commonly used in the pharmacotherapy of cardiovascular disorders. In the present study these drugs were investigated in the rat septic shock model. In vivo hemodynamic parameters were recorded using a data acquisition system in endotoxin-induced septic shock in rats. The animals were followed for 5 h and blood pressure, rectal temperature, and ECG were recorded. Blood samples were collected at 1 h and 5 h time points after the injection of endotoxin, and serological samples were stored at −25°C. Subsequently, tumor necrosis factor-α, interleukin-10 (enzyme-linked immunosorbent assay), and nitrite (Griess reagent) were determined in these serological samples. Significant correlations were observed between these humoral factors and the disordered hemodynamic factors. A reversal of changes was observed in the levels of serum cytokines, nitrite levels, and hemodynamic parameters with verapamil and nifedipine preadministration (P < 0.05). Additionally, superoxide dismutase (SOD), catalase, and malondialdehyde (MDA) were determined in livers obtained from these animals at the end of the experiments, and these results were compared to hemodynamic parameters and cytokines. Nifedipine and verapamil increased the levels of MDA and SOD but did not change catalase activity.

Preventive Effects of Ginkgo biloba Extract on Ischemia-Reperfusion Injury in Rat Bladder

Aims: The aim of this experimental study was to evaluate the effects of Ginkgo biloba (EGb 761) on ischemia-reperfusion (I-R) injury in the rat bladder. Methods: A bladder I-R injury was induced by abdominal aorta occlusion by ischemia for 30 min, followed by 45 min reperfusion in rats. The rats were divided into four groups of 7 rats each; the control, I-R, and I-R groups were pretreated intraperitoneally with 50 or 100 mg/kg G. biloba 60 min before ischemia induction. Contractile responses to carbachol through isolated organ bath studies were recorded, histological sections were evaluated by light microscopy, and TUNEL staining was performed for the evaluation of apoptosis. Results: In the I-R group, the contractile responses of the bladder strips were lower than those of the control group (p < 0.01–0.001) and were restored by pretreatment with 100 mg/kg G. biloba (p < 0.05–0.001). Decreased polymorphonuclear leukocyte infiltration was detected in the G. biloba pretreatment groups when compared to the I-R group during histological evaluation. The ratio of TUNEL-positive nuclei was 1.84% in the I-R group, whereas it was decreased in both of the G. biloba pretreatment groups (p < 0.01, p < 0.01). Conclusion: Our data indicated that G. biloba has a preventive effect on I-R injury in rat urinary bladder.

Effects of tadalafil on hemorrhagic cystitis and testicular dysfunction induced by cyclophosphamide in rats.

Introduction: The protective and/or therapeutic potential of tadalafil (TDL) on cyclophosphamide (CP)-induced hemorrhagic cystitis (HC) and testicular dysfunction in rats was evaluated. Materials and Methods: The animals except from the control group were divided into four groups and treated with saline, or 1, 5 or 10 mg/kg TDL orally (CP, TDL1, TDL5 and TDL10 groups, respectively) before and after CP injection. Body and organ weights, sperm count, cGMP, nitric oxide (NO), IL-6 and IL-10 levels in serum and bladder tissue, and serum testosterone (T), LH and FSH levels were determined. The histological analysis of bladder and testis was performed and the number of apoptotic cells was determined. Results and Conclusion: The CP group had decreased cGMP and NO levels in the bladder, serum T level (p < 0.05) and sperm count (p < 0.001) and higher IL-6 levels in serum and bladder (p < 0.01). Treatment with TDL resulted in increased cGMP (p < 0.001), NO (p < 0.05) and serum T (p < 0.05) levels. Histological analysis of the CP group showed severe HC in bladder and testicular damage. TDL-treated animals showed a dose-dependent improvement in all of these histological impairments. In conclusion, a selective inhibitor of phosphodiesterase-5 enzyme, TDL, showed a protective and/or therapeutic effect on CP-induced HC and testicular dysfunction in rats.

Putative antinociceptive effect of alpha-tocopherol in mice

AbstractAlpha-tocopherol is an antioxidant which has been suggested to have anti-inflammatory and analgesic activities in humans. However, the anti-inflamatory and analgesic effetcs of alpha-tocopherol in mice had not been studied. Therefore, this study was designed to determine the antinociceptive doses of alpha-tocopherol in mice. In addition, this study aims to compare the activity of alpha-tocopherol with those of dipyrone and aspirin and to investigate the role of nitric oxide (NO) in the antinociceptive activity of alpha-tocopherol in mice. Hot plate, tail clip and tail flick tests were applied to evaluate the central antinociceptive activity using 1, 5, 25 and 100 mg/kg intraperitoneal doses of alpha-tocopherol. A dose-dependent antinociceptive activity was observed at low doses, the most effective dose was 25 mg/kg. Furthermore, it was observed that co-administration of L-arginine (100 mg/kg) with alpha-tocopherol (25 mg/kg) reduced the antinociceptive activity and this activity was compared with ...

Functional Effects of Alagebrium (ALT-711)–Isolated Rat Carotid Artery

Objective In our study, the effects of glycosylated protein cross-link breaker, alagebrium was investigated on isolated rat carotid artery using myography. Alagebrium showed vasodilator effect on carotid artery rings; particularly, this effect was significantly increased in endothelium-intact rings. Materials and Methods To clarify the vasodilator mechanism of alagebrium, different antagonists such as N(G)-Nitro-L-arginine methyl ester (L-NAME), glibenclamide, indomethacin, metoprolol, propranolol, tetraethylammonium, and calcium channel activator BAYK-8644 were used to reverse this effect. Results Relaxation% responses to alagebrium were more significantly increased in intact endothelium than in denuded arteries. Blocking vasodilation related to channels (K-ATP, PGI2, BKca) and receptors (ß1, ß2) did not reverse the relaxation response to alagebrium. Vasodilator response to alagebrium was only slightly decreased after L-NAME incubation and significantly decreased after BAYK-8644 incubation. Conclusion Results of present study suggest that the mechanism of alagebrium-induced vasodilator effect may include the blockage of L-type calcium channels and partially of the nitric oxide synthase enzyme.

Chronopharmacological evaluation of the antinociceptive activities of aspirin and dipyrone in mice

AbstractA large number of physiological rhythms are controlled by the central nervous system, including hormone secretion. The potency and toxicity of many drugs also change according to the time when they are administered. There are also some studies of the biological rhythms in pain sensitivity. In the present study, central and peripheral antinociceptive effects of aspirin and dipyrone, commonly used analgesics, were evaluated chronopharmacologically in mice. The central antinociceptive activities of these drugs administered intraperiotoneally (100 mg/kg) were investigated in mice using tail clip, tail flick and hot plate tests, and the peripheral antinociceptive activities of these drugs were investigated using a stretching test with acetic acid when the drugs were administered at 9.00 a. m. or 9.00 p. m. The central nociception was not different between the two groups, while the sensitivity to pain was significantly greater with the acetic acid test (p < 0.05) at night than in the daylight in the con...