Article

Effect of chronic treatment of carvedilol on oxidative stress in an intracerebroventricular streptozotocin induced model of dementia in rats

Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh, India.
The Journal of pharmacy and pharmacology 12/2009; 61(12):1665-72. DOI: 10.1211/jpp/61.12.0012
Source: PubMed

ABSTRACT Oxidative stress is emerging as an important issue in the pathogenesis of dementia. This study was conducted to investigate the possible neuroprotective effects of carvedilol against streptozotocin induced behavioural alterations and oxidative damage in rats.
An intracerbroventricular cannula was implanted in the lateral ventricles of male Wistar rats. Various behavioural (locomotor activity, Morris water maze task) and biochemical parameters (lipid peroxidation, nitrate concentration, catalase, acetylcholinesterase, reduced glutathione and protein) were assessed.
Intracerebroventricular administration of streptozotocin caused a significant memory deficit as evaluated in the Morris water maze task paradigms, and caused marked oxidative damage as indicated by significant increases in malondialdehyde and nitrite levels, and depletion of superoxide dismutase, catalase and reduced glutathione levels. It also caused a significant increase in acetylcholinesterase activity. Chronic administration of carvedilol (1 and 2 mg/kg, i.p.) for a period of 25 days starting 4 days before streptozotocin administration resulted in an improvement in memory retention, and attenuation of oxidative damage and acetylcholinesterase activity.
This study demonstrates the effectiveness of carvedilol in preventing cognitive deficits as well as the oxidative stress caused by intracerbroventicular administration of streptozotocin in rats. Carvedilol may have potential in the treatment of neurodegenerative diseases.

Download full-text

Full-text

Available from: Atish Prakash, May 07, 2014
0 Followers
 · 
81 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cerebral aging is often associated with the occurrence of neurodegenerative diseases leading to dementia. Animal models are critical to elucidate mechanisms associated to dementia and to evaluate neuroprotective drugs. Rats that received intracerebroventricular injection of streptozotocin (icv-STZ) have been reported as a model of dementia. In these animals, this drug induces oxidative stress and brain glucose metabolism impairments associated to insulin signal transduction failure. These mechanisms are reported to be involved in the pathogenesis of Alzheimer's disease and other dementia. Icv-STZ rats also display memory impairments. However, little is known about the precise location of the lesions induced by STZ administration. In this context, the present study characterized the cerebral lesions induced by two-doses of icv-STZ by using high-field magnetic resonance imaging to easily and longitudinally detect cerebral abnormalities and by using immunohistochemistry to evaluate neuronal loss and neuroinflammation (astrocytosis and microgliosis). We showed that, at high doses, icv-STZ induces severe and acute neurodegenerative lesions in the septum and corpus callosum. The lesions are associated with an inflammation process. They are less severe and more progressive at low doses. The relevance of high and low doses of icv-STZ to mimic dementia and evaluate new drugs is discussed in the final part of this article.
    PLoS ONE 09/2012; 7(9):e46196. DOI:10.1371/journal.pone.0046196 · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: New effective strategies and new highly effective neuroprotective agents are being searched for the therapy of human stroke and cerebral ischemia. The compound SMe1EC2 is a new derivative of stobadine, with enhanced antioxidant properties compared to the maternal drug. Carvedilol, a non-selective beta-blocker, possesses besides its cardioprotective and vasculoprotective properties also an antioxidant effect. We compared the effect of carvedilol and SMe1EC2, antioxidants with a similar chemical structure, in two experimental models of oxidative stress in young and adult rat brain tissue. SMe1EC2 was found to improve the resistance of hippocampal neurons to ischemia in vitro in young and even in 18-month-old rats and inhibited formation of protein carbonyl groups induced by the Fe(2+)/ascorbic acid pro-oxidative system in brain cortex homogenates of young rats. Carvedilol exerted a protective effect only in the hippocampus of 2-month-old rats and that at the concentration 10-times higher than did SMe1EC2. The inhibitory effect of carvedilol on protein carbonyl formation induced by the pro-oxidative system was not proved in the cortex of either young or adult rats. An increased baseline level of the content of protein carbonyl groups in the adult versus young rat brain cortex confirmed age-related changes in neuronal tissue and may be due to increased production of reactive oxygen species and low antioxidant defense mechanisms in the adult rat brain. The results revealed the new pyridoindole SMe1EC2 to be more effective than carvedilol in neuroprotection of rat brain tissue in both experimental models involving oxidative stress.
    Interdisciplinary toxicology 12/2010; 3(4):122-6. DOI:10.2478/v10102-010-0051-x
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective This study evaluated the effect of carvedilol (CRV) commonly used antihypertensive drugs on the antiepileptic drug sodium valproate (SVP) along with neurobehavioural co-morbidities in various models of epilepsy.Methods For this purpose, we used the Increasing Current Electroshock Seizure (ICES) test and Pentylenetetrazole (PTZ) test in mice. Additionally, adverse effects of combined treatment with the drugs in the Spontaneous Alternation Behavior (SAB) and rotarod were assessed. The levels of TBARS and the Reduced Glutathione (GSH) were determined in brains of mice for investigation of the oxidative stress. All drugs were administered orally.ResultsSVP (50 & 100 mg/kg) and CRV (1.25, 2.5 & 5.0 mg/kg) alone as well as in combination significantly enhanced the seizure threshold in the ICES test and PTZ test. CRV significantly increase the percentage alternation scores as compared to control group whereas combination of SVP with CRV did not affect the percentage alternation scores. In the present study, CRV and SVP alone as well as in combinations had no significant effect on motor parameters, at any of the given doses. CRV and SVP alone as well as in combination shown to inhibit the lipid peroxidation and increase in the level of GSH in brain tissue in a dose dependent manner which showed that it reduces the oxidative stress.Conclusion The current study suggests that CRV potentiate the anticonvulsant activity of VPA. Therefore, the observed interaction could be pharmacodynamics in nature.
    06/2013; 5(2):87–91. DOI:10.1016/j.dit.2013.05.003