Mohammed Arshaduddin

Vitamin E decreases valproic acid induced neural tube defects in mice

The present study was undertaken to investigate the effect of vitamin E on valproic acid (VPA) induced teratogenesis. Pregnant Balb mice were divided into six groups of 10-11 animals each. The mice in group 1 served as control and were injected with saline subcutaneously on day 8 of gestation, whereas, animals in group 2 received a single injection of VPA (700 mg/kg (s.c.)). Groups 3 and 4 received an oral administration of vitamin E in the doses of 250 and 500 mg/kg, respectively, 1 h before VPA injection. Group 5 and 6 were given vitamin E only, in the same doses as group 3 and 4. On day 18 of gestation, the mice were killed by cervical dislocation. Embryotoxicity was assessed by counting the number of implants, live and dead fetuses, resorptions, crown rump length and fetal body weight. The fetuses were observed for malformations including neural tube defects (excencephaly), open eye lid and micrognathae. VPA administration resulted in a significant reduction of the average live fetuses/litter, fetal weight and crown rump length and a significant increase in malformations (excencephaly, open eye lid and micrognathae). Concomitant administration of vitamin E significantly attenuated VPA induced decrease in the fetal weight, crown rump length and malformations.

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.

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 animals 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.

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.

Baclofen attenuates harmaline induced tremors in rats

Recent experimental and clinical studies clearly suggest the role of gamma-aminobutyric acid (GABA) in the pathogenesis of tremors. The present study was undertaken to investigate the effect of baclofen, a GABA B receptor agonist on harmaline induced tremors. Four groups of female Wistar rats weighing 100+/-15 g were injected with harmaline (10 mg/kg, intraperitoneally) for inducing experimental tremors. The animals in groups 2, 3 and 4 were given baclofen by gavage at doses of 2.5, 5 and 10 mg/kg, respectively, half an hour before harmaline administration, whereas, the rats in group 1 served as control and received water. The latency of onset, intensity and duration of tremor and electromyographic (EMG) responses were recorded. Treatment with baclofen resulted in a dose dependent decrease in the intensity of tremor. Our EMG study also revealed a significant decrease in the amplitude of tremors in baclofen treated rats. A highly significant increase in latency of onset of tremor was observed in the rats treated with high dose (10 mg/kg) of baclofen only. This study clearly suggests beneficial effects of baclofen in harmaline induced tremors.

Functional recovery and vitamin E level following sciatic nerve crush injury in normal and diabetic rats.

Extensive biochemical data document the involvement of oxygen derived free radicals (ODFR) in recovery following neurotrauma as well as diabetic neuropathy. Vitamin E is considered as one of the principle protective mechanism against oxidative damage in neuronal tissue. The present study was undertaken to determine the association between functional recovery and vitamin E levels following sciatic nerve crush injury in normal and diabetic rats. The sciatic nerve of normal and streptozotocin (STZ) induced diabetic rats was crushed using a haemostat. The walking track analysis and vitamin E levels were recorded on 10, 20 and 30th day. Maximum functional deficiency and depletion of vitamin E in sciatic nerve was observed on 10th day following crush injury in both normal and diabetic animals. A progressive motor recovery and repletion of vitamin E was observed on day 20 and 30 following injury in both diabetic and normal rats. The functional recovery was slower whereas vitamin E level was higher in diabetic animals as compared to normal injured rats during healing phase suggesting that vitamin E alone may not be an efficient indicator of oxidative stress during regeneration of axons following trauma in diabetic rats.

Effect of Selenium and Vitamin E on Iminodipropionitrile Induced Dyskinesia in Rats

The present study was undertaken to determine the effect of combination of selenium and vitamin E on experimentally induced dyskinesia in rats. The dyskinetic syndrome was produced in 4 groups of 6 male rats each weighing 250-300g by intraperitoneal (ip) administration of iminodipropionitrile (IDPN) in doses of 100 mg/kg body weight daily for 12 days. A group of 6 rats (group 1) served as control and received normal saline only. The rats in group 2 (IDPN only) received normal saline (ip) 30 minutes before the administration of IDPN. The animals in groups 3, 4 and 5 received selenous acid (5 mumol/kg), vitamin E (500 mg/kg p.o.) and a combination of selenous acid and vitamin E respectively, daily, 30 minutes before IDPN for 12 days. Twenty four hours after the last dose of IDPN, the dyskinetic behavior including vertical head movements (retrocollis), horizontal head movements (laterocollis), circling and backwalking of each rat was studied for a period of 10 minutes. Immediately after behavioral studies, the animals were sacrificed and brains were dissected out for the analysis of conjugated dienes, lipid hydroperoxides and vitamin E. The results of this study showed that treatment of rats with IDPN only for 12 days produced dyskinetic syndrome in all the rats characterized by vertical and horizontal head movements, circling and backwalking. Concomitant treatment of rats with vitamin E and selenium individually reduced IDPN induced dyskinesia, and the symptoms were almost completely absent when the combination of these two agents was used.(ABSTRACT TRUNCATED AT 250 WORDS)

Dipyridamole attenuates the development of iminodipropionitrile-induced dyskinetic abnormalities in rats

The present investigation was undertaken to study the effect of dipyridamole on experimental dyskinesia in rats. The movement disorders were produced by intraperitoneal administration of iminodipropionitrile (IDPN) in the dose of 100 mg/kg per day for 12 days. Dipyridamole was administered orally, daily 30 min before IDPN in the doses of 0.5 g/kg, 1 g/kg, and 1.5 g/kg bodyweight in three different groups of rats. Twenty-four hours after the last dose of IDPN, animals were observed for neurobehavioral changes including vertical and horizontal head weaving, circling, backwalking, grip strength, and righting reflex. Immediately after behavioral studies brain specimens were collected for analysis of vitamin E, conjugated dienes, and lipid hydroperoxides as indices of oxygen-derived free radical (OFR) production. Our results showed that concurrent use of dipyridamole significantly protected rats against IDPN-induced neurobehavioral changes in a dose-dependent manner. Treatment of rats with dipyridamole inhibited IDPN-induced decrease of vitamin E and increase in conjugated dienes and lipid hydroperoxides in brain. These findings suggest the involvement of OFR in dipyridamole induced protection against the development of IDPN dyskinesia. Further studies are warranted to determine the role of dipyridamole as a prophylactic agent against the drug induced dyskinetic abnormalities.

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.

Effect of lidocaine on harmaline-induced tremors in the rat.

The present study was undertaken to investigate the effect of lidocaine on harmaline-induced tremors in the rat. Four groups of Wistar rats weighing 45-50 g were injected with harmaline (50 mg/kg i.p.) for inducing experimental tremors. The rats in group 1 served as control, whereas the animals in groups 2, 3, and 4 were also given lidocaine i.p. at doses of 12.5, 25, and 50 mg/kg, respectively, 10 min after the onset of tremors (therapeutic study). In a separate four groups of animals intraperitoneal lidocaine injection was given 10 min before harmaline (prophylactic study) in the same dose regimen as mentioned above. The latency of onset, intensity, and duration of tremor and electromyographic responses were recorded. Lidocaine dose dependently attenuated harmaline-induced tremors in rats. The latency period was increased, and duration and intensity of harmaline-induced tremors was reduced by lidocaine. Our electromyography (EMG) study also revealed a decrease in the amplitude of harmaline-induced tremors in lidocaine-treated rats. In conclusion, the results of this study clearly suggest beneficial effects of lidocaine in harmaline-induced tremors.