The effect of early and long-term propranolol therapy on learning and memory in mice.

Propranolol is the treatment of choice for infantile hemangioma. We investigated the effects of long-term propranolol use in early infancy on learning and memory later in life in mice. At three weeks of age, mice were randomly divided into six experimental groups. Groups 1 and 2 (controls) received only saline for 21 days. Groups 3 and 4 received propranolol (2.5 mg/kg) for 21 days. Groups 5 and 6 received propranolol (5 mg/kg) for 21 days. Groups 1, 3 and 5 were tested at the end of 21 days of treatment (week 6). However, groups 2, 4 and 6 received a 2-week break and then (week 8) exposed to tests. In the Morris water maze test, propranolol (2.5 and 5 mg/kg) dose-dependently increased the time spent in the target quadrant in mice at weeks 6 and 8. However, propranolol did not affect the swimming speed in both time periods. There were no significant effects of propranolol on the number of errors evaluated during the radial arm maze tests. In conclusion, long-term use of propranolol in early infancy did not disrupt the learning and memory of mice.

Silibinin Effect on Methotrexate-Induced Hepatotoxicity in Rats.

OBJECTIVE: Hepatotoxicity is one of the major side effects of methotrexate and limits its use. In this study, we investigated the hepatoprotective effect of silibinin and the role of oxidative stress markers and cytokines on high-dose methotrexate-induced hepatotoxicity in rats. MATERIALS AND METHODS: In this study, rats were randomly divided into 5 groups (n=7). Methotrexate (20 mg/kg, intraperitoneally) was administered on the first day in all groups except control. Silibinin was injected for 5 days to methotrexate-silibinin25, methotrexate-silibinin50, and methotrexate-silibinin100 groups at a dose of 25, 50, and 100 mg/kg/day, respectively. On the sixth day, blood and liver samples were obtained and rats were sacrificed. Serum total antioxidant capacity, total oxidant status, total thiol, native thiol, alanine aminotransferase, aspartate transaminase, bilirubin, albumin, tumor necrosis factor-alpha, and interleukin-10 levels were measured. In addition, a histopathological evaluation of liver tissues was performed. RESULTS: Methotrexate reduced total antioxidant capacity and increased disulfide/total thiol ratio. Histopathologic examination revealed that methotrexate increased hepatic damage and 50 mg/kg/dose of silibinin prevented inflammatory cell infiltration in particular. CONCLUSION: Our results suggest that silibinin (50 mg/kg/day) may reduce the hepatic damage in methotrexate-induced hepatotoxicity in rats by increasing antioxidant capacity.

Bio-element status in children with acute rheumatic fever: before treatment and after clinical improvement.

Acute rheumatic fever (ARF) is an autoimmune multisystem disease. Bio-elements are required in different quantities by an organism to maintain its physiologic function. Monitoring the status of bio-elements is critical in human health. This study aimed to determine possible changes in levels of bio-elements in children with ARF before and after treatment. Levels of trace and major elements in children with ARF were investigated. The study included 33 children with ARF (17 boys and 16 girls) and 20 healthy control children (11 boys and 9 girls). The ages ranged from 5 to 16 years (mean 11.4 ± 3.82 years) in the study group and from 6 to 15 years (mean, 10.7 ± 3.22 years) in the control group. Trace and major element concentrations (total of 14 elements) in the serum were measured by inductively coupled plasma-optical emission spectroscopy. Before treatment, the levels of the major elements potassium (K) and magnesium (Mg) in children with ARF were higher than in the control group, whereas the calcium (Ca) level was lower. Before treatment, the levels of trace elements iron (Fe), selenium (Se), zinc (Zn), aluminum (Al), and barium (Ba) were lower, whereas the copper (Cu), beryllium (Be), cadmium (Cd), chromium (Cr), gallium (Ga), and strontium (Sr) levels were higher in the serum of the patients with ARF than in the control patients. The major findings show that the homeostasis of some trace and major elements were altered in the children with ARF and that these alterations may be a contributing factor in the pathogenesis of this disease.

Protective effect of Matricaria chamomilla on ethanol-induced acute gastric mucosal injury in rats.

The antiulcerogenic and antioxidant properties of Matricaria chamomilla L. (Compositae) hydroalcoholic extract (MCE) on ethanol-induced gastric mucosal injury were investigated in rats. After the induction of gastric mucosal injury, all groups were sacrificed; the gastric ulcer index was calculated, and malondialdehyde (MDA) and reduced glutathione (GSH) in whole blood and gastric tissue, and serum ascorbic acid, retinol, and beta-carotene levels were measured in all groups. Pretreatment with MCE at some doses significantly reduced gastric lesions. Again, some doses of MCE significantly reduced the MDA, and significantly increased GSH levels in gastric tissue or whole blood. Serum beta-carotene and retinol levels were significantly higher in the 200 mg/kg MCE-administered group with respect to control. As a result, MCE clearly has a protective effect against ethanol-induced gastric mucosal lesions, and this effect, at least in part, depends upon the reduction in lipid peroxidation and augmentation in antioxidant activity.

Does dexmedetomidine reduce secondary damage after spinal cord injury? An experimental study.

The aim of this experimental study was to investigate the possible protective effect of dexmedetomidine (DEX) on traumatic spinal cord injury (SCI). Twenty-two New Zealand rabbits were divided into three groups: sham (no drug or operation, n = 6), Control [SCI + single dose of 1 mL saline intraperitoneally (i.p), after trauma; n = 8] and DEX (SCI + 1 microg/kg dexmedetomidine in 1 mL, i.p, after trauma, n = 8). Laminectomy was performed at T10 and balloon angioplasty catheter was applied extradurally. Four and 24 h after surgery, rabbits were evaluated by an independent observer according to the Tarlov scoring system. Blood, cerebrospinal fluid (CSF), tissue samples from spinal cord were taken for biochemical and histopathological evaluations. After 4 h of SCI, all animals in control or DEX treated groups became paraparesic. On the other hand, 24 h after SCI, partial improvements were observed in both control and DEX treated groups. Traumatic SCI leads to increase in the lipid peroxidation and decreases enzymatic or nonenzymatic endogenous antioxidative defense systems. Again, SCI leads to apoptosis in spinal cord. DEX treatment slightly prevented lipid peroxidation and augmented endogenous antioxidative defense systems in CSF or spinal cord tissue, but failed to prevent apoptosis or neurodeficit after traumatic SCI. Therefore, it could be suggested that treatment with dexmedetomidine does not produce beneficial results in SCI.

Dantrolene can reduce secondary damage after spinal cord injury.

The aim of this experimental study was to investigate the possible protective effects of dantrolene on traumatic spinal cord injury (SCI). Twenty-four New Zealand rabbits were divided into three groups: Sham (no drug or operation, n = 8), Control (SCI + 1 mL saline intraperitoneally (i.p.), n = 8), and DNT (SCI + 10 mg/kg dantrolene in 1 mL, i.p., n = 8). Laminectomy was performed at T10 and balloon catheter was applied extradurally. Four and 24 h after surgery, rabbits were evaluated according to the Tarlov scoring system. Blood, cerebrospinal fluid and tissue sample from spinal cord were taken for measurements of antioxidant status or detection of apoptosis. After 4 h SCI, all animals in control or DNT-treated groups became paraparesic. Significant improvement was observed in DNT-treated group, 24 h after SCI, with respect to control. Traumatic SCI led to an increase in the lipid peroxidation and a decrease in enzymic or non-enzymic endogenous antioxidative defense systems, and increase in apoptotic cell numbers. DNT treatment prevented lipid peroxidation and augmented endogenous enzymic or non-enzymic antioxidative defense systems. Again, DNT treatment significantly decreased the apoptotic cell number induced by SCI. In conclusion, experimental results observed in this study suggest that treatment with dantrolene possess potential benefits for traumatic SCI.

Dantrolene exerts protective activity in double and triple combination with nimodipine, ruthenium red and basilene blue in bilirubin-induced neurotoxicity in cell culture of rats.

In the present study, dantrolene, nimodipine, basilen blue, and ruthenium red were tested in experimental bilirubin toxicity in cortical cell culture of rats. Neurotoxicity was induced by 10(-4) M bilirubin. Basilen blue in the highest concentration of 10(-4) M was determined as the most protective agent when applied alone. Dantrolene alone was found surprisingly ineffective in all doses tested. But it was found very protective both in double and triple combinations. Nimodipine, basilen blue, and ruthenim red neuroprotective potentials were enhanced by adding dantrolene into the media. Best double combination was determined as dantrolene plus ruthenium red. On the other hand, most useful triple combination was found as dantrolene plus nimodipine plus basilen blue. As a result, dantrolene wasn't found to be effective alone, while it seems most potential compound in combined application in bilirubin-induced neurotoxicity. The importance of calcium intrusion was confirmed in bilirubin-induced neurotoxicity.

Time-dependent effects of dantrolene on motor evoked potentials in experimental spinal cord injuries.

Objectives:Traumatic spinal cord injury (SCI) is a significant clinical problem with numerous secondary complications and perpetual deficits. No potent treatment is currently available to fully repair motor and other neurological functions. We studied the effects of dantrolene (DNT) at different time points, on the motor-evoked potentials (MEPs) and the apoptosis response in spinal cord injury. Methods:The study was conducted on a total of 38 rabbits divided into five main groups.These were group 1 (sham): only laminectomy (n = 6), group 2 (SCI): laminectomy and traumatic SCI (n = 8), group 3 (DNT 0h): just after the SCI, DNT 10 mg/kg I.P. (n = 8), group 4 (DNT 1h): 1 h after the SCI, DNT 10 mg/kg I.P. (n = 8), and group 5 (DNT 4h): 4 h after the SCI, DNT 10 mg/kg I.P. (n = 8). Results: DNT, which was administered as the treatment, had a therapeutic effect on the motor function. This effect was observed by recording neural transmission obtained via the Tarlov test and a transcranial magnetic stimulator by using the values of the MEPs. A significant decrease was histopathologically observed in the apoptotic cell count. Discussion: The electrophysiological efficacy of our model of trauma as SCI has been complemented with the significant differences between the control group and the SCI group. This creates a need for electrophysiological studies to be conducted in the future because effects, even at a minimum level, may play an important role in finding an applicable medicine for SCI.

Protective effects of dantrolene and methylprednisolone against spinal cord injury-induced early oxidative damage in rabbit bladder: A comparative experimental study.

BACKGROUND: Spinal cord injury (SCI) may cause dysfunction in the bladder and many distal organs due to systemic inflammatory response and oxidative stress-related injury. OBJECTIVES: We investigated the preventive effects of dantrolene (DNT) and methylprednisolone (MP) on stress-induced tissue damage in rabbit bladder with SCI. MATERIAL AND METHODS: A total of 35 rabbits were included in this study and they were divided into 5 groups: group 1 - control, group 2 - SCI only, group 3 - SCI and DNT, group 4 - SCI and MP, and group 5 - SCI and DNT+MP. Twenty-four hours after SCI, the bladders of these rabbits were removed and the histopathologic changes in the bladder were examined under a light microscope. Additionally, malondialdehyde (MDA), glutathione (GSH), and nitric oxide (NO) levels were evaluated as antioxidant agents both in bladder tissue and in blood. RESULTS: Compared to the control group, there was an increase in edema and congestion in all groups. The least amount of edema was observed in the group receiving DNT and the least amount of congestion was observed in the group receiving combined treatment (group 5). No superiority was found between the drug-receiving groups in terms of reducing MDA level in blood and tissue after SCI. The most successful group was the group receiving combined drug therapy in terms of increasing the blood GSH level, which was significantly decreased after SCI. After SCI, blood NO level increased significantly in all groups. Nitric oxide levels in the bladder tissue significantly decreased in the groups receiving DNT and combination therapy and fell in the control group. CONCLUSIONS: Dantrolene and MP may have potential benefits against oxidative damage in the bladder after SCIs because of their anti-inflammatory and antioxidant effects. In particular, the combined use of DNT and MP at different doses can be considered a treatment strategy.

Beneficial effects of Foeniculum vulgare on ethanol-induced acute gastric mucosal injury in rats.

AIM: To examine the anti-ulcerogenic and antioxidant effects of aqueous extracts of Foeniculum vulgare (FVE) on ethanol-induced gastric lesions in rats. METHODS: FVE was administered by gavage at doses of 75, 150 and 300 mg/kg, and famotidine was used at the dose of 20 mg/kg. Following a 60 min period, all the rats were given 1 mL of ethanol (80%) by gavage. One hour after the administration of ethanol, all groups were sacrificed, and the gastric ulcer index was calculated; whole blood malondialdehyde (MDA) and reduced glutathione (GSH), serum nitrate, nitrite, ascorbic acid, retinol and beta-carotene levels were measured in all the groups. RESULTS: It was found that pretreatment with FVE significantly reduced ethanol-induced gastric damage. This effect of FVE was highest and statistically significant in 300 mg/kg group compared with the control (4.18 +/- 2.81 vs 13.15 +/- 4.08, P < 0.001). Also, pretreatment with FVE significantly reduced the MDA levels, while significantly increased GSH, nitrite, nitrate, ascorbic acid, retinol and beta-carotene levels. CONCLUSION: FVE has clearly a protective effect against ethanol-induced gastric mucosal lesion, and this effect, at least in part, depends upon the reduction in lipid peroxidation and augmentation in the antioxidant activity.

Pyridoxine may protect the cerebellar granular cells against glutamate-induced toxicity.

In the present study, the possible protective effect of the pyridoxine against glutamate-induced neurotoxicity in cerebellar granular cell culture of rat pups is investigated for its therapeutic potential. Glutamate (10(-7) M) was administered to cerebellar granular cell cultures that were prepared from one-day-old Sprague-Dawley rats. The neuroprotective effect of pyridoxine was examined. Pyridoxine at the doses of 10(-8), 10(-7), 10(-6), and 10(-5) M was introduced into the culture flasks before inclusion of glutamate. Pyridoxine at the doses of 10(-8) M and 10(-7) M significantly reduced glutamate cytotoxicity. A 10(-7) M dose of pyridoxine proved to be more effective than a 10(-8) M dose. The present study demonstrates that pyridoxine may protect glutamate-induced neurotoxicity. Neuroprotective effect of pyridoxine, at least in part, may result from its anti-glutamatergic activity. Pyridoxine merits further investigation as a therapeutic option in hypoxic-ischemic brain injury.

Effects of long-term treatment with haloperidol, clozapine and aripiprazole on mice isolated vas deferens.

PURPOSE: Sexual dysfunction is a common condition in patients taking antipsychotics and is the most bothersome symptom and adverse drug effect, resulting in a negative effect on treatment compliance. Pharmacology research into human ejeculatory disorders is limited to clinical studies with registered drugs affecting the ejaculation process; therefore, animal research has become the need. We aimed to investigate the effects of haloperidol, clozapine and aripiprazole on serotonin, noradrenaline, adenosine triphosphate (ATP) and potassium chloride (KCl)-induced contractions of the vas deferens in order to evaluate the effect of haloperidol, clozapine and aripiprazole on the contraction of the vas deferens. METHODS: Male inbred BALB/c ByJ mice aged 7 weeks upon arrival to the laboratory were used in this study. Haloperidol, clozapine, aripiprazole, serotonin, noradrenaline, ATP and KCl were dissolved in 0.9% physiological saline. The mice were randomly divided into experimental groups as follows: saline; haloperidol 0.125 mg/kg; haloperidol 0.25 mg/kg; clozapine 1.25 mg/kg; clozapine 2.5 mg/kg; aripiprazole 3 mg/kg; aripiprazole 6 mg/kg. Mice were treated by ip injection of drugs during 21 days. Mice receiving only the vehicle ip (0.9% saline) during 21 days served as control group (n = 7). Each experimental group consisted of 7 mice. After 21 days of treatment, epididymal and prostatic portions of vas deferens were surgically dissected free and immersed in 20-mL organ baths containing Krebs' solution. The effects of chronic treatment with haloperidol (0.125 and 0.25 mg/kg), clozapine(1.25 and 2.5 mg/kg) and aripiprazole (3 and 6 mg/kg) were investigated on serotonin [10 (-8) to 10 (-4) M], noradrenaline [10 (-8) to 10 (-4) M], ATP [10 (-8) to 10 (-4) M] and 80 mM KCl-induced contractile responses in the epididymal and prostatic portions of mice isolated vas deferens strips. Statistical comparison between the groups was performed using ANOVA supported by Dunnett's post hoc test. RESULTS: Serotonin-induced contractile responses were significantly increased in the epididymal and prostatic portions of the vas deferens obtained from the haloperidol-treated group and clozapine-treated group. However, aripiprazole treatment had no effect on serotonin responses in both epididymal and prostatic portions of mice vas deferens. On the other hand, haloperidol and clozapine treatments significantly inhibited both noradrenaline and ATP-induced contractions of the prostatic and epididymal portions of the mice vas deferens, but had no effect on KCl-induced contractions of the vas deferens in both portions. There were no significant differences in KCl-induced contractile responses among the groups. CONCLUSIONS: These results revealed that induced contractions of vas deferens were affected after chronic treatment with haloperidol and clozapine but not aripiprazole. Serotonergic, noradrenergic and purinergic receptors may, at least in part, contribute to changes in vas deferens contractions in mice with chronic treatment of haloperidol and clozapine but not aripiprazole.

Protective effect of L-carnitine against bilirubin-induced neuronal cell death.

There is growing evidence that glutamate receptor-mediated injury plays a crucial role in bilirubin neurotoxicity. L-carnitine (LC) has been shown to prevent glutamate-induced toxicity in neuronal cell culture. The purpose of this study is to assess whether LC is able to prevent bilirubin neurotoxicity. Unconjugated bilirubin at different concentrations was administered to cerebellar granular cell cultures prepared from 1-day-old Sprague-Dawley rats. The neuroprotective effect of LC was examined. LC at doses of 10(-6), 10(-5), 10(-4) and 10(-3) M was applied to culture flasks. LC at a dose of 10(-4) M significantly blocked bilirubin neurotoxicity. On the other hand, LC significantly increased bilirubin toxicity at a higher dose (10(-3) M). LC at the doses of 10(-5) and 10(-6) M was found to be ineffective. 10(-4) M LC decreased bilirubin-induced neuronal cell death from 47.72+/-3.68 to 27.23+/-5.14%, (P=0.003). The present study demonstrates, for the first time, that LC protects against bilirubin neurotoxicity in a dose-dependent manner in cerebellar granular cell culture of rats. Further research is needed to confirm our findings and to clarify the mechanisms responsible for the protective effect of LC.

Protective effects of dantrolene against myocardial injury induced by isoproterenol in rats: biochemical and histological findings.

PURPOSE: We investigated whether dantrolene might protect the heart against myocardial injury (MI) induced by isoproterenol (ISO), using an experimental model in rats. METHODS: Twenty-eight rats were randomized to treatment with saline only (control group, n=8), ISO only (ISO group, n=8), low-dose dantrolene (LDD)+ISO (LDD group, n=6) and high-dose dantrolene (HDD)+ISO (HDD group, n=6). ISO (150 mg/kg/day, s.c.), LDD (5 mg/kg/day, i.p.) and HDD (10 mg/kg/day, i.p.) were given once a day for two consecutive days. At the end of the second day, blood samples were taken from abdominal aorta shortly after the rats were anesthetised for cardiac troponins T (cTnT) and I (cTnI) assay, and the hearts were removed and observed microscopically. RESULTS: cTnT and cTnI levels were increased in the ISO group when compared with the control group (p<0.001). LDD and HDD significantly reduced cTnT and cTnI levels when compared with the ISO group. Elevations of cTnT and cTnI appeared to relate to the severity of histological changes. The rate of animals that exhibited marked MI was higher in the ISO group than in the control group (p<0.001). The rats in both LDD and HDD groups showed less histological changes when compared to the ISO group (p<0.01). There was no significant difference between the control group and both LDD and HDD groups. CONCLUSIONS: This study shows that dantrolene has a significant effect in the protection of the heart against MI induced by ISO. We believe that pretreatment with dantrolene may contribute to developing novel strategies in the cardiotoxicity animal models and in the prevention of the cardiotoxic effects of elevated levels of catecholamines.

Effects of ziprasidone, SCH23390 and SB277011 on spatial memory in the Morris water maze test in naive and MK-801 treated mice.

Introduction: Patients with schizophrenia have cognitive dysfunctions; positive psychotic symptoms are the primary purposes for schizophrenia treatment. Improvements in cognitive function should be a characteristic of all newly developed drugs for the treatment of schizophreniawith dementia. Thus,we investigated the effects of the second-generation antipsychotic ziprasidone, dopamine D1 antagonist SCH-23390 and dopamine D3 antagonist SB-277011 on spatial learning and memory. Materials and methods: Male inbred mice were used. The effects of ziprasidone, SCH-23390 and SB-277011 were investigated using the Morris water maze test. Results: Ziprasidone (0.5 and 1mg/kg), SCH-23390 (0.05 and 0.1 mg/kg) and SB-277011 (10 and 20 mg/kg) had no effect on the time spent in the target quadrant in naive mice.MK-801 (0.1mg/kg) significantly decreased the time spent in the target quadrant. The time spent in the target quadrant was significantly prolonged by Ziprasidone (0.5 and 1 mg/kg) and SCH-23390 (0.1 mg/kg), but not with SB-277011 (20 mg/kg) in MK-801-treated mice. Ziprasidone (0.5 and 1mg/kg), SCH-23390 (0.05 and 0.1 mg/kg) and SB-277011 (10 and 20 mg/kg) had no effect on themean distance to the platformin naivemice.MK-801 significantly increased themean distance to the platform. Ziprasidone (1 mg/kg) and SCH-23390 (0.1 mg/kg) significantly decreased the mean distance to the platform in MK-801-treated mice, but SB-277011 (20 mg/kg) didn't. MK-801 significantly increased the total distance moved. Ziprasidone (0.5 and 1 mg/kg), SCH-23390 (0.05 and 0.1 mg/kg) and SB-277011 (10 and 20 mg/kg) had no effect on the total distance moved in naive mice. Ziprasidone (1 mg/kg) and SCH-23390 (0.1 mg/kg) significantly decreased the total distance moved in MK-801-treated mice, but SB-277011 (20 mg/kg) didn't. Conclusions: The second-generation antipsychotic drug ziprasidone and D1 antagonist SCH23390, but not the D3 antagonist SB277011, might be clinically useful for the treatment of cognitive impairments in patients with schizophrenia.

Melatonin protects rat liver against irradiation-induced oxidative injury.

The aim of this study was to investigate the antioxidant roles of different doses of melatonin (5 and 10 mg x kg (-1) ) against gamma-irradiation-caused oxidative damage in liver tissue after total body irradiation (TBI) with a single dose of 6.0 Gy. Fifty adult rats were divided into 5 equal groups, 10 rats each. Groups I and II were injected with 5 and 10 mg x kg (-1) of melatonin, and group III was injected with an isotonic NaCl solution. Group IV was injected with only 5 mg x kg (-1) of melatonin. Group V was reserved as a sham control. Following a 30-min-period, 6.0 Gy TBI was given to groups 1, 2 and 3 in a single fraction. The liver malondialdehyde (MDA) levels, super oxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were measured in all groups. TBI resulted in a significant increase in the liver tissue MDA levels and a decrease of SOD and GSH-Px activities. The results demonstrated that the liver tissue MDA levels in irradiated rats that were pretreated with melatonin (5 or 10 mg x kg (-1) ) were significantly decreased, while the SOD and GSH-Px activities were significantly increased. Decreasing the MDA levels by melatonin was dose dependent, but the liver tissue SOD and GSH activities were not. The data obtained in this study suggest that melatonin administration prior to irradiation may prevent liver damage by irradiation.

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.

Antioxidant, antimicrobial, antiulcer and analgesic activities of nettle (Urtica dioica L.).

In this study, water extract of nettle (Urtica dioica L.) (WEN) was studied for antioxidant, antimicrobial, antiulcer and analgesic properties. The antioxidant properties of WEN were evaluated using different antioxidant tests, including reducing power, free radical scavenging, superoxide anion radical scavenging, hydrogen peroxide scavenging, and metal chelating activities. WEN had powerful antioxidant activity. The 50, 100 and 250 microg amounts of WEN showed 39, 66 and 98% inhibition on peroxidation of linoleic acid emulsion, respectively, while 60 microg/ml of alpha-tocopherol, exhibited only 30% inhibition. Moreover, WEN had effective reducing power, free radical scavenging, superoxide anion radical scavenging, hydrogen peroxide scavenging, and metal chelating activities at the same concentrations. Those various antioxidant activities were compared to standard antioxidants such as butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), quercetin, and alpha-tocopherol. In addition, total phenolic compounds in the WEN were determined as pyrocatechol equivalent. WEN also showed antimicrobial activity against nine microorganisms, antiulcer activity against ethanol-induced ulcerogenesis and analgesic effect on acetic acid-induced stretching.

Prevention of acute adriamycin cardiotoxicity by dantrolene in rats.

Possible preventive effect of dantrolene against the peroxidative damage in rat heart which was induced by the administration of an acute dose of adriamycin (ADR, 20 mg/kg, i.p.) has been examined. Forty-eight hours after ADR administration, biochemical changes including the activities of serum creatine kinase isoenzyme (CK-MB), lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) and the levels of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in heart tissue were measured. Pretreatment of rats with dantrolene, given i.p. 30 min prior to ADR injection, substantially reduced the peroxidative damage in the myocardium, and markedly lowered the serum CK-MB, LDH and AST. The protective effects obtained by dantrolene administration, however, were not complete and did not reach those of the control group. Dantrolene, at 5 mg/kg, was useful to obtain significant protective effects, while the protector effect of higher dantrolene dosing level (10 mg/kg) was weak or absent. These results suggest that, at least in part, due to antioxidative properties, dantrolene may provide a significant protective effect against acute ADR-induced cardiotoxicity.

In vitro effects of dantrolene sodium and verapamil on noradrenaline-induced contractions of rabbit aorta and their interactions.

The effects of dantrolene sodium (0.1 to 10 microM) and verapamil (0.01 to 1 microM) administered alone or together (1 microM verapamil, 0.1 to 10 microM dantrolene sodium) were investigated in isolated rabbit thoracic aorta precontracted with 0.1 microM noradrenaline (NA). Verapamil plus dantrolene sodium produced a dose-dependent inhibition of aortic strips contractions evoked by NA, and all concentrations of dantrolene sodium significantly decreased the inhibitory effect of 1 microM verapamil (p < 0.001, ANOVA). In conclusion, dantrolene sodium and verapamil inhibited 0.1 microM noradrenaline-evoked aorta contractions, and all doses of dantrolene sodium decreased the inhibitory effect of 1 microM verapamil in a dose-dependent manner.