Can dantrolene protect spinal cord against ischemia/reperfusion injury? An experimental study.

BACKGROUND: The aim of this experimental study was to investigate the possible protective effect of dantrolene on neuronal injury induced by aortic ischemia/reperfusion (I/R). METHODS: Nineteen rabbits were divided into three groups: sham (group 1, n = 5, no I/R), control (group 2, n = 7, only I/R) and dantrolene (group 3, n = 7, dantrolene + I/R). Abdominal aortic occlusion between the renal arteries and iliac bifurcations was carried out for 30 min. The spinal cord functions of the subjects were assessed using the Tarlov Scale. Blood and cord tissue samples were taken for biochemical and histopathological evaluation. RESULTS: Tarlov scores in group 3 were significantly higher than in group 2 ( P < 0.05). In group 3, the MDA levels of the spinal cord decreased significantly compared to those of group 2 ( P < 0.05). In rabbits with I/R (group 2), the GSH levels of the spinal cord decreased significantly compared to those of group 1 ( P < 0.01), but dantrolene pretreatment significantly prevented a decrease in GSH levels. Histopathological examination showed that group 3 had less vascular proliferation, hemorrhage, edema and neuron loss than group 2. CONCLUSIONS: It was concluded that dantrolene applied after ischemia might help protect the spinal cord against ischemia/reperfusion injury.

Effect of dantrolene on lipid peroxidation, lutathione and glutathione-dependent enzyme activities in experimental otitis media with effusion in guinea pigs.

The aims of our study were to assess whether the increased oxidative stress in experimental otitis media with effusion (OME) induced by histamine was reflected erythrocytes and middle ear effusion fluid by lipid peroxidation; to survey the alterations in antioxidant enzyme activities in experimental OME; and to determine the effect of dantrolene on this oxidative stress. Erythrocyte and middle ear effusion malondialdehyde (MDA) level, erythrocyte glutathione (GSH) and glutathione peroxidase (GSH-Px), glutathione reductase (GRD) and glutathione-S-transferase (GST) activities were measured in three groups of seven guinea pigs, 3 hours after injection of 0.1 mL of histamine (or saline) into the middle ear in guinea pigs with OME (experimental group), in a dantrolene sodium group and in a control group. Erythrocyte and effusion MDA levels in the dantrolene group were significantly lower than those of the experimental group. Erythrocyte GSH-Px, GST, GRD activities, and GSH levels were significantly higher in the dantrolene group than in the experimental group. Dantrolene sodium decreased the erythrocyte and effusion MDA levels, on the other hand, it increased the GSH and GSH-dependent enzymes. These findings suggest that reactive oxygen species (ROS) play a role in histamine-induced OME. Pre-treatment with dantrolene sodium increases antioxidant enzymes activities and decreases formation of MDA, the indicator of lipid peroxidation, in histamine-induced OME.

Sedative, anticonvulsant and behaviour modifying effects of Centranthus longiflorus ssp. longiflorus: a study of comparison to diazepam.

The aqueous extract of Centranthus longiflorus ssp. longiflorus (CLE) was investigated for sedative, anticonvulsant and behaviour modifying activity using thiopental sleeping, caffeine induced convulsion and forced swimming depression tests. When the effects of the aqueous extract of CLE (100 mg/kg) was compared to diazepam, it showed similar sedative and anticonvulsant effects to those produced by diazepam (5 mg/kg).

In vitro antioxidant properties of dantrolene sodium.

Dantrolene sodium is a skeletal muscle relaxant, which inhibits intracellular Ca2+ release from the sarcoplasmic reticulum. The aim of this study is to examine possible in vitro antioxidant effects of dantrolene sodium. For this reason, the in vitro antioxidant effects of dantrolene sodium were studied using thiocyanate methods. Additionally, the reducing power and free radical scavenging activity were determined. Dantrolene sodium showed strong antioxidant activity in the linoleic acid emulsion system. The antioxidant activity increased with an increasing amount of dantrolene sodium (50, 100, 250 microg). The 50, 100 and 250 microg samples of dantrolene sodium showed 55%, 70% and 82% inhibition on peroxidation of linoleic acid, respectively. On the other hand, the 250 microg sample of alpha-tocopherol showed 62% inhibition of peroxidation of linoleic acid. Like antioxidant activity, the reducing power of dantrolene sodium increased in a dose-dependent manner. The reducing power of dantrolene was statistically significant vs control, but lower than butylated hydroxytoluene (BHT) and quercetin. Although dantrolene sodium had free radical scavenging activity this was not statistically significant. In contrast to dantrolene sodium, quercetin and butylated hydroxyanisole (BHA) had highly potent free radical scavenging activities and those were statistically significant. According to the these results, it may be said that antioxidant effect of dantrolene sodium is more related to its antioxidant activity in linoleic acid emulsion and reducing power, than to its free radical scavenging activity. These properties may be major reasons for the inhibition of lipid peroxidation.

Antiulcerogenic effect of Hippophae rhamnoides L.

The antiulcerogenic effect of a hexane extract (HRe-1) from Hippophae rhamnoides (Eleagnaceae) was tested on indomethacin- and stress-induced ulcer models. As a result HRe-1 was found to be active in preventing gastric injury.

The effects of newly synthesized pyrazole derivatives on formaldehyde-, carrageenan-, and dextran-induced acute paw edema in rats.

The antiinflammatory effects of 10 newly synthesized pyrazole derivatives on formaldehyde-induced rat paw edema were investigated. The most effective of them (K-3) was investigated again in dextran- and carrageenan-induced paw edema. In formaldehyde-induced paw edema, K-3 50, 100, and 200 mg/kg p.o. inhibited the edema by 48.9% (p<0.002), 68.7% (p<0.001), and 79.1% (p<0.001), respectively, 3 h after administration. In dextran-induced paw edema, the same dose of K-3 produced 27.1% (p<0.05), 46.8% (p<0.01), and 63.8% (p<0.002) inhibition, respectively. In the carrageenan-induced paw edema test, K-3 100 mg/kg decreased the inflammatory response by 52.0% after 4 h. Acute toxicity studies revealed that K-3 was nontoxic up to an oral dose of 2500 mg/kg.

Effects of metamizol and magnesium sulfate on enzyme activity of glucose 6-phosphate dehydrogenase from human erythrocyte in vitro and rat erythrocyte in vivo.

OBJECTIVE: Effects of metamizol and magnesium sulfate on erythrocyte glucose 6-phosphate dehydrogenase enzyme activity were investigated in in vitro and in vivo conditions. METHODS: For in vitro studies, glucose 6-phosphate dehydrogenase was purified from human erythrocyte and rats were used for in vivo studies. Enzyme activity was determined according to the Beutler method by using a spectrophotometer at 340 nm. RESULTS: The results of in vitro study showed that their mean K(i) values were 6.35 x 10(-3) M for metamizol and 1.32 x 10(-2) M for magnesium sulfate and their inhibition types were uncompetitive. I(50) value was 17 mM for metamizol and 50 mM for magnesium sulfate in in vitro study. In the case of in vivo studies, 200 mg/kg metamizol inhibited the enzyme activity by 40% during the first 1.5 h (p < 0.05), and 225 mg/kg magnesium sulfate significantly inhibited the enzyme activity throughout 24 h (p < 0.01). CONCLUSION: The results of this study suggested that metamizol and magnesium sulfate have significant inhibition effect on the activity of glucose 6-phosphate dehydrogenase enzyme in both in vivo and in vitro.

Effect of the aqueous extract of Rumex patientia on xylol and hyaluronidase induced capillary permeability compared to indomethacin.

In this study, the effect of an aqueous extract of Rumex patientia L. (Polygonaceae) (D-1) on capillary permeability which was induced by xylol and hyaluronidase was investigated. Experiments were conducted on rabbits according to Monakova and Matusis methods. The effects of D-1 were compared to those of indomethacin, which was used as a control throughout the experiment. Both D-1 (100 mg/kg) and indomethacin (10 mg/kg) were administered orally. As a result, D-1 inhibited capillary permeability, which was induced by xylol and hyaluronidase, and it was found that it was as effective as indomethacin.

Effect of cefaperazone/sulbactam and ampicillin/sulbactam on the in vitro activity of human erythrocyte glucose-6-phosphate dehydrogenase.

We investigated the effects of the antibiotic drugs cefaperazone/sulbactam and ampicillin/sulbactam on the in vitro activity of the enzyme glucose-6-phosphate dehydrogenase (G6PD). The enzyme was purified from human erythocytes using 2',5' ADP-Sepharose 4B affinity gel. The enzymatic activity was measured spectrophotometrically at 340 nm, according to the method of Beutler. The I50 values were determined from Activity % - [Drug] graphs, and the Ki constants and inhibition types for each drug were determined using Lineweaver-Burk graphs. The I50 value was 13.5 mg/ml for cefaperazone/sulbactam and 36 mg/ml for ampicillin/sulbactam. The Ki constants were 10.16 for ampicillin/sulbactam and 38.22 for cefaperazone/sulbactam. Cefaperazone/sulbactam competitively inhibited G6PD activity, whereas ampicillin/sulbactam non-competitively inhibited the activity of the enzyme.

Effects of some medical drugs on enzyme activities of carbonic anhydrase from human erythrocytes in vitro and from rat erythrocytes in vivo.

In this study, firstly, the effects of sodium ampicillin, magnesium sulfate, and sodium dipyrone on human carbonic anhydrase (HCA) (EC 4.2.1.1.) isozymes have been investigated in vitro. Human erythrocyte CA-I and CA-II isozymes were separately purified by affinity chromatography. Inhibition or activation effects of three different medical drugs on HCA isozymes were determined using the CO(2)-Hydratase method by plotting activity %vs [medical drug]. I(50)values of the drugs exhibiting inhibition effects were found by means of these graphs. It was observed on HCA-I hydratase activity that sodium ampicillin and sodium dipyrone showed inhibition and activation effects, respectively. However, magnesium sulfate showed no effect. It was observed on HCA-II hydratase activity that sodium ampicillin and magnesium sulfate showed an inhibition effect, and sodium dipyrone showed an activation effect. In addition, in vivo studies were performed for these medical drugs in Sprague-Dawley rats. It was demonstrated that CA in erythrocytes was significantly inhibited by these drugs in 3 h.