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.

0 Bookmarks
 · 
58 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Alzheimer's disease (AD), the most common form of dementia, is characterized by the loss of normal functions of brain cells and neuronal death, ultimately leading to memory loss. Recent accumulating evidences have demonstrated the therapeutic potential of anti-diabetic agents, such as dipeptidyl peptidase-4 (DPP-4) inhibitors, for the treatment of Alzheimer's disease (AD), providing opportunities to explore and test the DPP-4 inhibitors for treating this fatal disease. Prior studies determining the efficacy of Pterocarpus marsupium (PM; Fabaceae) and Eugenia jambolana (EJ, Myrtaceae) extracts for ameliorating type 2 diabetes have demonstrated the DPP-4 inhibitory properties indicating the possibility of using of these extracts even for the treating AD. Therefore, in the present study, the neuroprotective roles of PM and EJ for ameliorating the streptozotocin (STZ) induced AD have been tested in rat model. Experimentally, PM and EJ extracts, at a dose range of 200 and 400mg/kg, were administered orally to STZ induced AD Wistar rats and cognitive evaluation tests were performed using radial arm maze and hole-board apparatus. Following 30 days of treatment with the extracts, a dose- and time-dependent attenuation of AD pathology, as evidenced by decreasing amyloid beta 42, total tau, phosphorylated tau and neuro-inflammation with an increase in glucagon-like peptide-1 (GLP-1) levels was observed. Therefore, PM and EJ extracts contain cognitive enhancers as well as neuroprotective agents against STZ induced AD.
    Behavioural brain research 03/2014; · 3.22 Impact Factor
  • 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.
    Drug Invention Today. 06/2013; 5(2):87–91.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Lycopene has attracted significant research interest due to its beneficial therapeutic effects, which include anti-oxidant, neuro-protective and anti-cancer effects, but the mechanisms of its beneficial action is not clear so far. The present study was carried out to elucidate the neuroprotective effect of lycopene against the β-amyloid induced cognitive impairment and mitochondria oxidative damage in rats. β-amyloid (β-A1-42) was administered through intracerebroventricular (ICV) by using stereotaxic instrument in male Wistar rats. Lycopene (2.5 and 5mg/kg) was administrated for three weeks. Behavioral performances were conducted during the study. The rats were sacrificed on the 21(st) day following the last behavioral test and cytoplasmic fractions of hippocampus were prepared for the quantification of acetylcholinesterase, oxidative stress parameter, mitochondrial enzymes, and inflammatory mediator like TNF-α, Il-6 activities, caspase-3 and BDNF. ICV β-A1-42 resulted in poor memory retention in Morris water maze and caused marked oxidative stress as indicated by significant increase in oxidative, mitochondria damage, TNF-α, IL-6 and Caspase-3 activity. We also found that β-A1-42 induced animal altered BDNF level than control animals. Chronic administration of lycopene resulted in an improvement in memory retention, attenuation of mitochondrial-oxidative damage, reduced neuro-inflammation and restoration of BDNF level in β-A1-42 treated rats. These studies indicated that lycopene helps to protect β-A1-42 induced cognitive dysfunction and modulates amyloidogenesis.
    European journal of pharmacology. 07/2014;

Full-text

Download
12 Downloads
Available from
May 31, 2014