Effects of mirabegron on depression, anxiety, learning and memory in mice.

Mirabegron is the first b3-adrenoceptor agonist to enter clinical practice and has been approved for the treatment of symptoms of OAB. The aim of this study is to investigate whether the mirabegron has an effect on depression, anxiety, learning, and memory. We investigated the effects of mirabegron on depression, anxiety, learning and memory by using forced swimming test, elevated plus maze test, passive avoidance and Morris water maze in mice. Imipramine and mirabegron (3, 6 and 9 mg/kg) significantly reduced immobility time in forced swimming test. Diazepam and mirabegron (3, 6 and 9 mg/kg) significantly increased the time spent in open arms and the number of entries to the open arms in elevated plus maze test. Furthermore, cognitive performance impaired with scopolamine has been significantly improved with 9 mg/kg mirabegron. Mirabegron (6 and 9 mg/kg) significantly increased the time spent in the target quadrant in naive mice. While scopolamine significantly increased the swimming speed, mirabegron (9 mg/kg) significantly decreased the swimming speed in scopolamine-treated mice. Mirabegron might be clinically useful for the treatment of OAB in elderly patients that should use drugs against depression and anxiety, without disrupt learning and memory.

In vivo anti-ulcerogenic effect of okra (Abelmoschus esculentus) on ethanol-induced acute gastric mucosal lesions.

CONTEXT: Okra, Abelmoschus esculentus (L.) (Malvaceae), is a medicinal plant widely used in Turkish traditional medicine for the treatment of various diseases such as ulcers and gastritis. OBJECTIVE: In the present study, we evaluated the gastroprotective effect of okra against ethanol-induced acute gastric mucosal injury in animal models. MATERIALS AND METHODS: Wistar rats were treated with 500, 250 or 100 mg/kg okra; 20 mg/kg famotidine (Fam); and 75 mg/kg quercetin (Que). Following a 60 min period, all the rats were given 1 mL of ethanol (80%). One hour after the administration of ethanol, all groups were sacrificed. RESULTS: At 5000 mg/kg, the extract produced (okra) no signs of toxicity in animals. Okra 500, 250, 100, Fam 20 and Que 75 inhibited ulcer formation by 81.0, 67.5, 67.0, 76.3 and 72.4%, respectively. Okra 500 significantly decreased edema, hemorrhage and inflammation scores compared with the ethanol group (p < 0.05). The oxidant levels decreased significantly in the all study groups compared within ethanol group (p < 0.001). Serum ß-carotene and retinol levels significantly increased 40.2 and 45.4% in the okra 500 group. In okra 500, 250 and Fam 20 groups, apoptosis significantly decreased (p < 0.001), while okra 500, 250 and Fam 20 groups showed a higher percentage of cell proliferation compared with the ethanol group (p < 0.001). DISCUSSION AND CONCLUSIONS: Our in vivo data indicate that okra has a gastroprotective effect against ethanol and could reduce the gastric ulcer as seen from biochemical and histopathological results. We suggest that okra could be a possible therapeutic antiulcer agent.

Heparin for adhesion prevention: comparison of three different dosages with Seprafilm in a murine model.

BACKGROUND: This study aimed to assess the safety and effectiveness of different dosages of heparin for adhesion prevention by comparing with Seprafilm, in a murine model. MATERIALS AND METHODS: Seventy five Balb/c mice were randomized into five groups. Group C were reserved as controls, and 62.5 IU, 125 IU, 250 IU of heparin, and Seprafilm were intraperitoneally applied in studied groups. The severity and locations of adhesions were assessed after the sacrification on day 14. The cause of death was investigated to evaluate the side effects of the drugs. RESULTS: The death of 2 subjects due to peritonitis (1 in Group C, 1 in Group H62.5) left 14 subjects in Group C and Group H62.5 (P ≥ 0.05), and no hemorrhage related death was observed. The use of the products significantly reduced the severity score of adhesion and the number of animals, had adhesions in different locations of the abdominal cavity, when the results were compared with the control group (P < 0.05 for all comparisons). Higher dosages of heparin seemed to be more effective. The results in group S, groups H250 and H125 were quite similar. CONCLUSIONS: Relatively high doses (125 IU and 250 IU) of intra-abdominal heparin may be comparable in safety and effectiveness to Seprafilm in adhesion prevention in mice.

Contribution of the histaminergic receptor subtypes to histamine-induced cerebellar granular neurotoxicity.

In the present study, we investigated the effects of histamine and its specific H(1), H(2) and H(3) receptor blockers in cerebellar granular cell culture derived from rat pups. Histamine was applied at 10(-9),10(-8), 10(-7),10(-6), and 10(-5) M for 16 h into the cultures and the highest dose was found to be the most toxic one. Pheniramine (H(1) receptor blocker), ranitidine (H(2) receptor blocker) and thioperamide (H(3) receptor blocker) were applied at 10(-8), 10(-7), 10(-6), 10(-5) M into the flasks prior to histamine in the second step of the experiments. Also, the effect of all of the blockers together at 10(-5) M concentrations was tested on the toxicity induced by 10(-5) M histamine. The H(3) receptor blocker, thioperamide (10(-6) M) was demonstrated to be most effective histamine toxicity blocker. Histamine H(2) blocker, ranitidine, was found to attenuate histamine neurotoxicity at all doses tested, its most effective dose being the highest dose. On the other hand, H(1) blocker, pheniramine, was able to reverse the effect of histamine at 10(-6) and 10(-5) M, but it was found ineffective when given at 10(-9) and 10(-8) M. Combined application of H(1), H(2), and H(3) receptor blockers at 10(-5) M concentrations, 45 min before histamine addition into the flasks at 10(-5) M, was able to reduce cell death score but it was not as effective as H(3) blocker, thioperamide.

On the in vitro antioxidative properties of melatonin.

The aim of this study is to examine possible in vitro antioxidant effects of melatonin. Thus, the total in vitro antioxidant activity of melatonin was studied using a thiocyanate method. Additionally, the reducing power, the superoxide anion scavenging activity and free radical scavenging activity of melatonin were determined. Melatonin exhibited potent antioxidant activity in a linoleic acid emulsion system. The antioxidant activity increased with increasing concentrations of melatonin (50-500 microg). The 50, 100, 250 and 500 microg melatonin doses showed 41, 60, 86 and 99% inhibition of peroxidation of linoleic acid, respectively. On the other hand, a 500-microg dose of alpha-tocopherol showed 34% inhibition of peroxidation of linoleic acid. Like the total antioxidant activity, the reducing power of melatonin increased in a dose-dependent manner. The reducing power of melatonin was statistically significant versus control, but lower than butylated hydroxytoluene (BHT) or quercetin. Additionally, melatonin had potent superoxide radical scavenging activity and exhibited a higher superoxide radical scavenging activity than quercetin or BHT but lower than butylated hydroxyanisole (BHA). Melatonin's direct free radical scavenging actions may account, at least in part, for its ability to reduce lipid peroxidation. Melatonin may have utility in protecting stored foods from free radical-induced deterioration.

In vitro effects of some anesthetic drugs on enzymatic activity of human red blood cell glucose 6-phosphate dehydrogenase.

The study investigated in vitro effects of halothane, isoflurane, ketamine, sevoflurane, prilocaine, diazepam, and midazolam on enzymatic activity of human red blood cell glucose-6-phosphate dehydrogenase (G6PD; E.C. 1.1.1.49). G6PD was purified from human red blood cells by 2',5'-ADP-sepharose 4B affinity gel. Enzymatic activity was spectrophotometrically measured at 340 nm according to the method of Beutler. I50 values were determined from drug activity (%) - drug concentration curves. I50 values were as follows: 0.72 mM for isoflurane, 1.82 mM for sevoflurane, 0.38 mM for diazepam, and 0.0019 mM for midazolam. But halothane, ketamine and prilocaine had no inhibitory effect on the G6PD activity in in vitro.

Some drug effects on the activity of erythrocyte hexokinase and glucose 6-phosphate dehydrogenase enzymes in vitro and in vivo.

Effects of theophylline, lidocaine, cyclophosphamide, hyoscine N-butyl bromide, tranexamic acid and cytarabine on hexokinase (HK) from human erythrocytes have been investigated in vitro. In addition, in vivo effects of theophylline and lidocaine were investigated in rats. HK was purified from human red blood cells by DEAE-Sephadex A50 ion exchange chromatography. HK activity was measured spectrophotometrically at 25 degrees C in a system coupled with glucose 6-phosphate dehydrogenase, according to Beutler's method at 340 nm. Cyclophosphamide, hyoscine N-butyl bromide, tranexamic acid and cytarabine had no effects on human erythrocyte HK activity in in vitro conditions. On the other hand, human erythrocyte HK was inhibited by theophylline, but activated by lidocaine. IC50 value for theophylline was 0.013 M. In the case of in vivo studies, 6 mg kg(-1) of theophylline inhibited the rat HK activity by 43% at the first 1.5 h (p < 0.001). A dose of 5 mg kg(-1) of lidocaine activated the rat HK activity by 41% (p < 0.001), 22% (p < 0.001), and 11% (p < 0.05), at 1.5, 3 and 6 h, respectively.