Gastro protecting influence of Topiramate in ethanol produced gastric ulcers in rats.

BACKGROUND: Topiramate (TPM), an antiepileptic drug, is also effective against alcohol dependency, a crucial factor in forming gastric ulcers. There is an increased possibility of patients with compromised gastric conditions getting exposed to TPM, but its effect on gastric ulcers is unknown. This study investigates the implication of acute TPM in ethanol-produced gastric ulceration in rats. MATERIAL AND METHODS: The effect of TPM studied in male 200-225 g Sprague Dawley rats against ethanol-induced gastric ulcers and for gastric secretion and acidity. The factors assessed include gastric secretion and acidity, gastric ulcer score, biochemical and histological changes, NF-kB, and p53 expression. The analysis of data performed by using the Kruskal Wallis test and Dunnett's multiple comparison tests. RESULTS: TPM pretreatment showed gastroprotective effects. It significantly reduced ethanol-induced increased gastric secretion, acidity, and gastric ulcer index and prevented gastric mucus depletion. The ethanol-induced inflammation and apoptosis were also significantly decreased by reducing the increased gastric myeloperoxidase activity and the expression of NF-kB and p53. TPM pretreatment also reduced the ethanol-induced damage to the gastric histology in rats. CONCLUSION: TPM exerted a gastro-protective effect against ethanol-induced gastric ulcers mediated by reducing the gastric ulcer index, preventing a decrease of the mucus levels, reduction in inflammation, damage to gastric histology, and a decrease in the enhanced expression of NF-kB and TPM. Further detailed investigations are essential to understand the chronic influence of TPM on gastric ulcers.

Low-dose acute vanillin is beneficial against harmaline-induced tremors in rats.

OBJECTIVE: To study the effect of pretreatment with low doses of vanillin, a flavoring agent used as a food additive, on harmaline-induced tremor in rats. METHODS: Sprague Dawley rats (110 ± 5 g) were divided into groups of six animals each. Vanillin (6.25 mg, 12.5 mg, and 25 mg/kg) was administered by gavage to different groups of rats, 30 minutes before the induction of tremor. Harmaline (10 mg/kg, i.p.) was used for the induction of tremor. The latency of onset, duration, tremor intensity, tremor index, and spontaneous locomotor activity were recorded. A separate batch of animals was used for the determination of serotonin (5HT) and 5 hydroxyindole acetic acid (5HIAA) levels in the brain. RESULTS: Harmaline treatment resulted in characteristic tremor that lasted for more than 2 hours and decreased the locomotor activity of rats. Pre-treatment with vanillin significantly reduced the duration, intensity, and tremor index of harmaline-treated animals. Vanillin treatment also significantly attenuated harmaline-induced decrease in the locomotor activity. An increase in 5HT levels and the changes in 5HIAA/5HT ratio observed in harmaline treated rats were significantly corrected in vanillin pretreated animals. DISCUSSION: Vanillin in low doses reduces harmaline-induced tremor in rats, probably through its modulating effect on serotonin levels in the brain. These findings suggest a beneficial effect of vanillin in essential tremor.

Scorpion (Androctonus bicolor) venom exhibits cytotoxicity and induces cell cycle arrest and apoptosis in breast and colorectal cancer cell lines.

OBJECTIVES: The defective apoptosis is believed to play a major role in the survival and proliferation of neoplastic cells. Hence, the induction of apoptosis in cancer cells is one of the targets for cancer treatment. Researchers are considering scorpion venom as a potent natural source for cancer treatment because it contains many bioactive compounds. The main objective of the current study is to evaluate the anticancer property of Androctonus bicolor scorpion venom on cancer cells. MATERIALS AND METHODS: Scorpions were milked by electrical stimulation of telsons and lyophilized. The breast (MDA-MB-231) and colorectal (HCT-8) cancer cells were maintained in appropriate condition. The venom cytotoxicity was assessed by 3-(4,5-di-methylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay, and the cellular and nuclear changes were studied with propidium iodide and 4',6-diamidino-2-phenylindole stain, respectively. The cell cycle arrest was examined using muse cell analyzer. RESULTS: The A. bicolor venom exerted cytotoxic effects on MDA-MB-231 and HCT-8 cells in a dose- and duration-dependent manner and induced apoptotic cell death. The treatment with this venom arrests the cancer cells in G0/G1 phase of cell cycle. CONCLUSIONS: The venom selectively induces the rate of apoptosis in MDA-MB-231 and HCT-8 cells as reflected by morphological and cell cycle studies. To the best of our knowledge, this is the first scientific evidence demonstrating the induction of apoptosis and cell cycle arrest by A. bicolor scorpion venom.

Vanillin abrogates ethanol induced gastric injury in rats via modulation of gastric secretion, oxidative stress and inflammation.

Vanillin is commonly used as an additive in food, medicine and cosmetics, but its effect has not yet been studied in gastric injury. Therefore the effect of vanillin was studied in experimental gastric ulcer. Gastric secretion and acidity were studied in pylorus ligated rats. Ulcer index, levels of gastric mucus, malondialdehyde (MDA), myeloperoxidase activity (MPO), expression of nuclear factor kappa B (NF-κB) p65, and histopathological changes were determined in ethanol induced gastric ulcer. Pre treatment with vanillin significantly reduced gastric secretion (P < 0.001) and acidity (P < 0.0001) and gastric ulcer index scores (P < 0.001). and augmented the gastric mucosal defense. Vanillin significantly restored the depleted gastric wall mucus levels (P < 0.0001) induced by ethanol and also significantly attenuated ethanol induced inflammation and oxidative stress by the suppression of gastric MPO activity (P < 0.001), reducing the expression of NF-κB p65 and the increased MDA levels (P < 0.001). Vanillin was also effective in alleviating the damage to the histological architecture and the activation of mast cells induced by ethanol. Together the results of this study highlight the gastroprotective activity of vanillin in gastric ulcers of rats through multiple actions that include inhibition of gastric secretion and acidity, reduction of inflammation and oxidative stress, suppression of expression of NF-κB, and restoration of the histological architecture.

Aripiprazole an atypical antipsychotic protects against ethanol induced gastric ulcers in rats.

The present investigation was undertaken, to study the gastro-protective potential of aripiprazole (ARI) an atypical antipsychotic drug in ethanol induced gastric ulcers in rats. ARI (10, 30, 100 mg/kg) was tested for gastric secretion and antiulcer activity in different groups of male Sprague Dawley rats. Gastric secretion and acidity studies were performed in pylorus ligated rats while indices of gastric ulcers were measured in ethanol (1 ml-100%) induced gastric ulcers. Histological changes and the levels of gastric wall mucus, malondialdehyde (MDA), non-protein sulfhydryls (NP-SH), myeloperoxidase (MPO), and serotonin were used to assess ethanol induced gastric mucosal injuries. Exposure of rats to ethanol resulted in gastric mucosal injury and a high index of ulcer. Pretreatment with ARI significantly (P < 0.001), reduced the gastric lesions induced by ethanol and also resulted in a significant decrease in the gastric secretion, and total acidity in pylorus ligated rats. ARI also significantly attenuated the ethanol induced reduction in the levels of gastric wall mucus, and NP-SH (P < 0.001). The histological changes and the increased MDA and MPO activity were also significantly (P < 0.001) inhibited by ARI. Ethanol induced depletion in the levels of serotonin in the gastric tissue were also significantly restored by pretreatment with ARI (p < 0.001). ARI showed significant antiulcer and gastroprotective activity against ethanol induced gastric ulcers. The gastroprotective effects of ARI may be due to its anti-secretory, antioxidant and anti-inflammatory action and also due to the restoration of the depleted gastric serotonin levels.

Gastroprotective effect of minocycline in experimentally induced gastric ulcers in rats.

Minocycline (MCN), a semi-synthetic tetracycline derivative possesses pleiotropic effects and provides protection against a number of disease models. However its effect on gastric ulcers has not been studied. The present investigation was undertaken, to study the gastro-protective potential of MCN in experimentally induced gastric ulcers in rats. MCN (10, 30, 100 mg/Kg) was tested for gastric secretion and antiulcer activity in different groups of Wistar rats. Gastric secretion and acidity studies were performed in pylorus ligated rats while indices of gastric ulcers were measured in ethanol (1 ml-100%) and indomethacin (30 mg/kg), induced gastric ulcers. Histological changes and the levels of gastric wall mucus, malondialdehyde (MDA), non-protein sulfhydryl (NP-SH), and myeloperoxidase (MPO), were used to assess ethanol induced gastric mucosal injuries. Exposure of rats to ulcerogens resulted in gastric mucosal injury and a significant increase in the indices of ulcer. MCN conferred a protective effect against ethanol, and indomethacin induced gastric mucosal injuries. Treatment with MCN, resulted in a significant decrease in the amount of gastric secretion, and total acidity and significantly (P<0.001), reduced the gastric lesions induced by ethanol and indomethacin. MCN also significantly attenuated the ethanol induced reduction in the levels of gastric wall mucus, and NP-SH (P<0.001). The histological changes and the increased MDA and MPO activity were also significantly (P<0.001) inhibited by MCN. Minocycline showed significant antiulcer and gastroprotective activity against experimentally induced gastric ulcers. The gastroprotective effects of minocycline may be due to its anti-secretory, antioxidant and anti inflammatory action.

Clinical aspects and frequency of scorpion stings in the Riyadh region of Saudi Arabia.

OBJECTIVES: To study the clinical aspects and frequency of scorpion stings in Riyadh region of Saudi Arabia. METHODS: Clinical aspects and frequency of scorpion sting cases reporting to 2 referral hospitals in the Riyadh region of Saudi Arabia were analyzed during May 2006 to April 2008. Data on demographic status, date and time of sting, sting site, scorpion color, clinical manifestations, and treatment were collected. RESULTS: A total of 391 cases of scorpion stings were recorded from the 2-referral hospitals, 248 (63.4%) of were men and 143 (36.6%) were women. The 21-30 years age group was the worst affected, followed by 31-40 years, 11-20 years, and <10 years age groups. Larger number of stings occurred during the summer months, at nights, and on distal limbs. Most of the patients reached the hospital within one hour of the sting. The yellow scorpions were responsible for a larger number of stings than the black scorpions. Seventy-five percent of the patients showed local signs and symptoms and 25% demonstrated systemic manifestations of poisoning. Most of the patients were treated with antivenom. CONCLUSION: The high prevalence of scorpion stings largely with mild signs/symptoms and without any mortality suggests the predominance of weak venomous scorpion species in the Riyadh region. Therefore, the protocol of managing scorpion-sting patients with anti-venom irrespective of the intensity of manifestations warrants a detailed review.

Trolox ameliorates 3-nitropropionic acid-induced neurotoxicity in rats.

3-nitropropionic acid (3-NPA) is a naturally occurring neurotoxin produced by legumes of the genus Astragalus and Arthrium fungi. Acute exposure to 3-NPA results in striatal astrocytic death and variety of behavior dysfunction in rats. Oxidative stress has been reported to play an important role in 3-NPA-induced neurotoxicity. Trolox is a potent free radical chain breaking antioxidant which has been shown to restore structure and function of the nervous system following oxidative stress. This rapid and efficient antioxidant property of trolox was attributed to its enhanced water solubility as compared with alpha-tocopherol. This investigation was aimed to study the effect of trolox against 3-NPA-induced neurotoxicity in female Wistar rats. The animals received trolox (0, 40 mg, 80 mg and 160 mg/kg, orally) daily for 7 days. 3-NPA (25mg/kg, i.p.) was administered daily 30 min after trolox for the same duration. One additional group of rats served as control (vehicle only). On day 8, the animals were observed for neurobehavioral performance. Immediately after behavioral studies, the animal's brains were dissected out for histological studies. Lesions in the striatal dopaminergic neurons were assessed by immunohistochemical method using tyrosine hydroxylase immunostaining. Administration of 3-NPA alone caused significant depletion of striatal dopamine and glutathione, whereas, the levels of thiobarbituric acid reactive substance (TBARS) and nitric oxide (NO) were significantly increased suggesting an elevated level of oxidative stress. Trolox significantly and dose-dependently protected animals against 3-NPA-induced neurobehavioral, neurochemical and structural abnormalities. These results clearly suggest that protective effect of trolox against 3-NPA-induced neurotoxicity is mediated through its free radical scavenging activity.

Exacerbation of harmaline-induced tremor by imipramine.

Imipramine is a well-established tricyclic antidepressant which was first approved for the treatment of depression in the late fifties. Antidepressant effect of imipramine is attributed to inhibition of serotonin (5HT) and noradrenaline (NA) reuptake in brain. These monoamines have been implicated in a variety of neurological disorders including tremor. In the present investigation attempt was made to study the effect of imipramine on harmaline-induced tremor in rats. Male Sprague Dawley rats weighing 115+/-2.5 g were given harmaline (10 mg/kg, i.p.) alone or along with imipramine (30 min before harmaline) in doses of 60 and 90 mg/kg respectively. The latency of onset, intensity and duration of tremor and EMG were recorded. To substantiate the role of 5HT in aetiopathology of tremor the above experiment was repeated in the rats pretreated with P-chlorophenylalanine (PCPA), a potent 5HT depleter. The levels of 5HT and 5-hydroxyindole acetic acid (5HIAA) in the brain stem were measured using high performance liquid chromatography. Imipramine dose-dependently exacerbated the duration, intensity and amplitude of EMG following harmaline-induced tremor. Imipramine treatment further decreased harmaline-induced 5HT turnover in the brain stem. However, this was statistically insignificant. Depletion of 5HT produced a significant reduction in the intensity and duration of harmaline-induced tremor. In conclusion, this study suggests that imipramine exacerbates harmaline-induced tremor. Clinical use of imipramine for the treatment of depression in patients who also suffer from tremors may require a close monitoring.

Citalopram, a selective serotonin reuptake inhibitor augments harmaline-induced tremor in rats.

Citalopram, a serotonin reuptake inhibitor (SSRI) is one of the widely used antidepressants. Apart from its antidepressant activity citalopram is also used for anxiety, panic disorders, obsessive-compulsive disorder and behavioral disturbances of dementia. Tremor is the second most common neurological adverse effect in patients receiving treatment with SSRIs. Use of these agents in depressed patients with essential tremor has not been studied. The present study was undertaken to investigate the effect of chronic citalopram treatment on harmaline-induced tremors in rats. Female Sprague-Dawley rats weighing 70+/-2 g were given citalopram in doses of 0, 10, 20 and 40 mg/kg by gavage for 2 weeks. On the 15th day, the rats were given harmaline (10 mg/kg, i.p.) 30 min after the last dose of citalopram. The latency of onset, intensity and duration of tremor and EMG were recorded. Serotonin (5HT) and 5-hydroxy indole acetic acid (5HIAA) were measured in brain stem. Citalopram dose dependently exacerbated the duration, intensity and amplitude of EMG of harmaline-induced tremor. A significant decrease in 5HT turnover (5HIAA/5HT ratio) in the brain stem was observed suggesting a possible role of serotoninergic impairment in citalopram-induced augmentation of harmaline-induced tremor. Clinical implications of these observations warrant further investigation.

Fluconazole attenuates lung injury and mortality in a rat peritonitis model.

OBJECTIVE: Acute lung injury following peritonitis constitutes an enigmatic clinical problem with no specific therapy. Recently, immunomodulators such as azole compounds have been shown to attenuate shock-related tissue injury. The present investigation was undertaken to study the effect of fluconazole on acute lung injury and survival following faecal peritonitis in rats. SUBJECTS: Male Wistar rats weighing 225-235 g. DESIGN AND SETTING: Faecal peritonitis (Fp) was produced in four groups of adult male Wistar rats by intraperitoneal administration of non-sterile faecal suspension (1:1 w/v saline). A fifth group of rats was given sterile faecal material (SFM), which served as control. INTERVENTIONS: Rats in Fp groups were given fluconazole in doses of 0 mg/kg, 3 mg/kg, 10 mg/kg, and 30 mg/kg by gavage 30 min before induction of peritonitis. The control animals received an equal volume of distilled water. MEASUREMENTS AND RESULTS: Survival over a period of 72 h, oxidative stress, neutrophil activity, and lung injury were measured. This study showed a 90% survival in the fluconazole-treated group compared to only 20% survival in untreated rats (P<0.008 log-rank test). The lungs of animals with Fp showed massive pathological changes including intraalveolar oedema, fibrosis, and mixed inflammatory cell infiltrate. These changes were dose-dependently attenuated by fluconazole. Enhanced oxidative stress (P<0.001) and neutrophil activity in the peritoneal fluid and lung (P<0.001) in Fp animals was dose-dependently reduced by fluconazole. CONCLUSION: This study clearly suggests the role of neutrophils in Fp-induced tissue injury/mortality, which may be dose-dependently, attenuated by fluconazole.

2-deoxy-D-glucose attenuates harmaline induced tremors in rats.

Neuronal hyperactivity in essential tremor is accompanied by high energy demand in cerebellum, medulla and the thalamus. It has been suggested that brain regions that have increased metabolic demands are highly vulnerable to interruptions in glucose metabolism. In the present investigation attempt was made to study the effect of 2-deoxyglucose (2DG) a glycolytic pathway inhibitor on harmaline induced tremor in rats. Wistar rats of either sex weighing 100+/-3 g were given harmaline (10 mg/kg, i.p.) alone or along with 2DG (15 min before harmaline) in doses of 300, 600 and 900 mg/kg, respectively. The latency of onset, intensity and duration of tremor following harmaline administration were recorded. Neurobehavioral responses, electromyography (EMG) and levels of blood glucose and cerebellar serotonin (5HT) were determined after 40 min of harmaline administration. 2DG significantly and dose dependently attenuated severity of harmaline induced tremors and amplitude of EMG. Treatment of rats with 2DG alone reduced the locomotor activity, however, no significant change was observed in grip strength, landing foot splay, air righting reflex and response to tactile stimuli. Harmaline alone and along with 2DG had no effect on behavioral parameters except a decrease in landing foot splay. 2DG produced a dose-dependent hyperglycemia and attenuated harmaline induced increase in cerebellar 5HT levels. Our results clearly suggest the protective effect of 2DG in harmaline induced tremor. Further studies are warranted to assess the role of glucoprivation in the suppression of neuronal excitability in tremors.

Effect of acute caffeine on severity of harmaline induced tremor in rats.

Recent studies suggest an association between caffeine consumption and tremor. However, the available literature is scanty and inconclusive. The present study was undertaken to investigate the effect of acute caffeine treatment on harmaline induced tremors in the rat. Four groups of male Sprague-Dawley rats (six animals in each group) weighing 88+/-2 g were administered harmaline (10 mg/kg, intraperitoneally (i.p.)) for inducing experimental tremors. The rats in group 1 served as controls and received normal saline, whereas the animals in groups 2, 3 and 4 were given caffeine (i.p.) at doses of 50, 100 and 150 mg/kg, respectively 60 min after harmaline administration. The latency of onset, intensity and duration of tremor and electromyographic (EMG) responses were recorded. Treatment of rats with caffeine resulted in a significant increase in the intensity and duration of harmaline induced tremors. Caffeine also enhanced the EMG amplitude in harmaline treated animals. In conclusion, the results of this study suggest that acute treatment with caffeine significantly potentiates the severity of harmaline induced tremors in rats.

Diethyldithiocarbamate (DEDC) impairs neuronal recovery following sciatic nerve injury in rats.

Purpose: Diethyldithiocarbamate (DEDC) is a substituted dithiocarbamate that is metabolically interconvertible with disulfiram (Ant-abuse). In recent years DEDC has received considerable attention because of its clinical applications and potential role in mediating both the toxic and therapeutic actions of disulfiram which is frequently used for alcohol aversion therapy. DEDC is known for its multiplicity of action that exerts both pro- and antioxidant effects. In rodents DEDC has been shown to produce neuroprotective as well as neurotoxic effects. The purpose of this study was to examine the effect of DEDC on neurological recovery following sciatic nerve crush injury (SNCI) in rats. Methods: Adult female Wistar rats were subjected to SNCI with a haemostat under deep anaesthesia. The animals were orally treated with DEDC at the doses of 250 mg/kg, 500 mg/kg and 750 mg/kg body weight 1 hr before SNCI and then once daily for 60 days. The animals were observed for sciatic functional index (walking deficit), electrophysiological and histological changes. Vitamin E level was measured to deter-mine antioxidant status of sciatic nerve. Results: Crush injury to the sciatic nerve resulted in a significant impairment of functional response which gradually recovered over a period of 22 days. Treatment of animals with DEDC caused a significant delay in functional recovery which was accompanied by poor histo-logical and electrophysiological outcome. Prooxidant effect of DEDC is quite evident from a significant decrease in vitamin E levels in both injured and uninjured sciatic nerves. Conclusions: Our results demonstrate that exposure to DEDC adversely affects recovery from peripheral nerve injury. The delay may to some extent be attributed to DEDC induced oxidative stress.