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.

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.

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.

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.

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.

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.

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.

Prevention of cyclophosphamide-induced hemorrhagic cystitis by resveratrol: a comparative experimental study with mesna.

PURPOSE: Hemorrhagic cystitis (HC) is the most common urotoxic side effect of cyclophosphamide (CP). The aim of this study was to compare the classical efficacy of mesna (2-mercaptoethane sulfonate sodium) with three different doses of resveratrol (RES) on cyclophosphamide-induced HC in rats. METHODS: Forty-six male Sprague-Dawley rats were divided into six groups. Group 1 served as a negative control (sham). Five groups received a single dose of cyclophosphamide (150 mg/kg) intraperitoneally at the same time. Groups 2, 3, 4, 5, and 6 received only CP, CP + 20 mg/kg RES, CP + 40 mg/kg RES, CP + 80 mg/kg RES, and CP + classical protocol of three doses of mesna (30 mg/kg three times), respectively. Antioxidants, cytokines, and malondialdehyde levels were measured in all groups. In addition, histopathological alterations in tissues were examined. RESULTS: CP administration induced severe HC with marked edema, hemorrhage, and inflammation in group 2. RES 20 mg/kg showed meaningful protection against bladder damage compared to the control group. It was seen that RES 40 mg/kg gave weaker protection but RES 80 mg/kg was not found to be effective. CONCLUSION: In conclusion, marked bladder protection was found in 20 and 40 mg/kg RES applications compared to the control group, but this protection was weaker than with mesna.

Evidence that the anxiolytic-like effects of the beta3 receptor agonist amibegron involve serotoninergic receptor activity.

Anxiety disorders are the most common behavioral disorders, and they exhibit high comorbidity rates. The aim of the present study was to confirm the effects of Amibegron, the first selective beta 3 adrenergic agent, on anxiety and to demonstrate that different serotoninergic receptor subtypes are involved in this effect. We administered the serotonin 5-HT1A receptor antagonist WAY-100635, the serotonin 5-HT2A receptor antagonist Ketanserin and the serotonin 5-HT3 receptor antagonist Ondansetron in mice and evaluated their performance in the elevated plus-maze test. Mice administered with Amibegron (5 and 10 mg/kg) showed a dose-dependent prolonged time spent in the open arms and an increase in the number of entries into the open arms during the elevated plus-maze (EPM) test. However, in the control mice, administration of WAY, Ketanserin and Ondansetron demonstrated no effect on the time spent in the open arms and the number of entries into the open arms. In addition, these treatments all significantly reversed the effect of the Amibegron-induced (10 mg/kg) increase in the time spent in the open arms. However, only WAY and Ketanserin treatments reversed the Amibegron-induced increase in the number of entries into the open arms. In conclusion, Amibegron exerted a significant anxiolytic effect, which was as effective as Diazepam, in mice during the EPM test. This effect of Amibegron may be mediated by interactions with the serotonin 5-HT1A, 5-HT2A and 5-HT3 receptors.

Involvement of serotonin receptor subtypes in the antidepressant-like effect of beta receptor agonist Amibegron (SR 58611A): an experimental study.

New therapeutic strategies against depression, with less side effects and thus greater efficacy in larger proportion of depressed patients, are needed. Amibegron (SR58611A) is the first selective ß3 adrenergic agent that has been shown to possess a profile of antidepressant activity in rodents. To investigate the involvement of serotonin receptors in the effects of amibegron, we used the serotonin 5HT1A receptor antagonist WAY-100635 (WAY) or serotonin 5HT2A-2C receptor antagonist ketanserin or serotonin 5HT3 receptor antagonist ondansetron in mice forced swimming test (FST). The locomotor activity was evaluated by measuring the total distance moved in the apparatus and the speed of the animals in the open field test. Imipramine (30mg/kg) significantly reduced immobility time compared to vehicle-treated group while amibegron (5 and 10mg/kg) dose dependently reduced immobility time in the FST. WAY(0.1mg/kg), ondansetron (1mg/kg), ketanserin(5mg/kg) had no effect on immobility time in naive mice while all of the drugs partially and significantly reversed amibegron (10mg/kg) induced decreasement in the immobility time in FST. None of the drugs alter locomotor activity in the open field test. The antidepressant-like effect of amibegron in the FST seems to be mediated by an interaction with serotonin 5-HT1A, serotonin 5-HT2A-2C and serotonin 5-HT3 receptors.

Royal jelly can diminish secondary neuronal damage after experimental spinal cord injury in rabbits.

The aim of this experimental study was to investigate the neuroprotective effect of Royal jelly (RJ) on traumatic spinal cord injury (SCI). Twenty-one New Zealand male rabbits, weighing between 2.5 and 3.0 kg were divided into three groups: Sham (no drug or operation, n = 7), Control (laminectomy+single dose of 1 ml/kg saline orally, after trauma; n = 7) and RJ (laminectomy+100mg/kg RJ, orally, after trauma, n = 7). Laminectomy was perfor med at T10 and balloon catheter was applied extradurally for traumatic SCI. Four and 24h 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. Four hours after SCI, all animals in control or RJ treated groups became paraparesic. Significant improvement was observed in RJ treated group, 24h after SCI, with respect to control. Traumatic SCI led to increase in the lipid peroxidation and decrease enzymic or non-enzymic endogenous antioxidative defense systems, and increase in apoptotic cell numbers. RJ treatment mostly prevented lipid peroxidation and also augmented endogenous enzymic or non-enzymic antioxidative defense systems. Again, RJ treatment significantly decreased the apoptotic cell number induced by SCI.

Serum and liver tissue bio-element levels, and antioxidant enzyme activities in carbon tetrachloride-induced hepatotoxicity: protective effects of royal jelly.

The liver is a vital organ, and its function is generally impaired by chemicals. Some natural compounds have a protective role against liver diseases such as royal jelly (RJ). To our knowledge, there are no data available on the effect of RJ therapy on the levels of bio-element metabolisms and antioxidant enzyme activities in the carbon tetrachloride (CCl(4))-induced liver damage. Therefore, in the present study, we have investigated the role of RJ therapy in the trace and major elements and antioxidant enzymes in CCl(4)-induced hepatotoxicity in rats. Antioxidant enzyme activities decreased in the CCl(4)-treated group more than they did in the sham and RJ-administered groups. Many bio-element levels were also reduced in only the CCl(4)-treated group. This showed that the depletion of trace elements was related to erythrocyte antioxidant enzyme activities. RJ administration clearly increased the trace and major element levels and antioxidant enzyme activities in RJ groups. RJ may be used as functional foods because of their naturally high antioxidant potential and rich element content.

The roles of melatonin and vitamin E plus selenium in prevention of oxidative stress induced by naloxone-precipitated withdrawal in heroin-addicted rats.

The therapeutic effects of melatonin or vitamin E plus Se (vE + Se) on the restrain of the heroin withdrawal-induced oxidative stress were studied. For this, rats were divided into ten groups. The rats were injected by fixed or variable doses of heroin for 16 consecutive days, and naloxone was given 1 h after the last heroin injection. One hour after naloxone administration, some groups were treated with melatonin or vE + Se. After 1 h this, blood samples were taken, and the levels of malondialdehyde (MDA) and reduced glutathione (GSH) in whole blood, ascorbic acid, α-tocopherol, retinol, ß-carotene, nitrite, nitrate, and ceruloplasmin levels in the serum were measured. Our findings showed that, naloxone administration precipitated the heroin withdrawal. This also increased the level of MDA and decreased the levels of GSH in blood. Melatonin or vE + Se administration prevented the rise in MDA levels and increased the GSH levels. On the other hand, there were some significant differences between α-tocopherol, retinol, ß-carotene, nitrite, nitrate, and ceruloplasmin levels of experimental groups. Results of present study showed that heroin withdrawal increased the lipid peroxidation and depressed endogenous antioxidative systems. Additionally, melatonin or vE + Se administrations prevented lipid peroxidation and augmented endogenous antioxidant defense systems.

Antioxidant enzyme and element status in heroin addiction or heroin withdrawal in rats: effect of melatonin and vitamin E plus Se.

Heroin use, withdrawal syndrome, and heroin-related deaths are still the most serious public health problems. Antioxidants and bio-elements are essential for metabolism in living organisms. To our knowledge, there are no data about the effect of antioxidant therapy on the levels of bio-elements and antioxidant enzymes in the naloxone (NX)-induced heroin withdrawal syndrome. Therefore, in the present study for the first time, we have investigated the role of antioxidant therapy, melatonin, and vitamin E plus Se, on the trace and major elements and antioxidant enzymes in the heroin addiction or heroin withdrawal in rats. Glutathione peroxidase levels were increased and catalase levels were decreased in the all study groups when compared to the sham group. The level of superoxide dismutase (SOD) in the fixed dose of heroin (FDH) given group was lower; however, in the variable doses of heroin (VDH) given group SOD level was higher. Furthermore, in withdrawal syndrome, Fe, Mg, Mn, and Ti levels were diminished and Al, Ca, and Cu levels were increased in the FDH+NX group. Moreover, Mg, Mn, and Se levels were also diminished and Al level was increased in the VDH+NX group. In conclusion, our results obviously indicated that heroin effected both bio-element status and antioxidant enzyme activities and, exogenous melatonin or vE+Se therapy might relieve on the element and antioxidant enzyme the destructive activity caused by heroin.

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.

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.

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 potential of Royal Jelly against carbon tetrachloride induced-toxicity and changes in the serum sialic acid levels.

Royal Jelly (RJ) is used in the Turkish folk medicine for the treatment of number of disorders. The present study describes the hepatoprotective and antioxidant activities of the RJ against carbon tetrachloride (CCl(4))-induced acute liver damage. Sprague-Dawley rats were used for the experiment. CCl(4) (0.8 ml/kg; s.c.) and RJ (50, 100, 200mg/kg; orally) were given every other day, for 20 days. Malondialdehyde, reduced glutathione in whole blood and tissues; ceruloplasmin, sialic acid, ascorbic acid, retinol, ß-carotene and liver enzymes levels in serum were measured. Additionally, histopathological alterations in the liver were examined. RJ exerted the significant protective effect on liver damage as well as on oxidative stress induced by CCl(4), resulting in reduced lipid peroxidation and improved endogenous antioxidant defence systems. It also reduced the elevated levels of liver enzymes. Histopathological study further confirmed the hepatoprotective effect of RJ, when compared with the CCl(4) treated control groups. In conclusion, present study reveals biological evidence that supports the use of RJ in the treatment of chemical-induced hepatotoxicity.

Tissue trace and major element levels in organophosphate insecticide fenthion (Lebaycid) toxicity in rats: prophylactic and therapeutic effect of exogenous melatonin.

Organophosphate compounds are very toxic chemicals and used in widespread applications. The present study was designed to examine the role of exogenous melatonin against organophosphate toxicity in tissues (brain, heart, jejunum, kidney, liver, lung, muscle and pancreas) trace and major element levels of rats. Trace and major element concentrations in the tissues were measured in the sham group, the control group, prophylaxis with the melatonin group and therapy with the melatonin group (TM) by inductively coupled plasma-optical emission spectroscopy. Statistically significant differences among the experimental groups were detected for some tissue trace and major element concentrations. In the brain tissue, the Al, Mn and Se concentrations in the sham group were significantly higher than those in the control group (p<0.05). In the heart tissue, the Cu, Mn and Se concentrations in the sham group were significantly increased than those in the control group (p<0.05). In the kidney tissue, trace and major element concentrations in the TM group were significantly lower than those in the sham group (Fe and Mn; p<0.05, Cu, Mo, Ni, Ti, V and Zn; p<0.01). In the liver, Mg, Al, Zn and Ca concentrations in the TM group were significantly higher than those in the fenthion-treated control group (p<0.01). In the muscle tissue, element concentrations in the TM group were significantly lower when compared with the sham groups (Ca and Si; p<0.01). The Al, Cr, Mo, Ni, Si and Zn element concentrations were markedly decreased in the control group as compared with the TM group in the pancreas tissue (p<0.01). In conclusion, according to the results of the present study the major findings are that the fenthion-treated rat's tissue element levels were effected and the melatonin may normalize the altered levels of some trace and major elements of the tissues in organophosphate toxicity.