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

Article (PDF Available) · December 2009with62 Reads
DOI: 10.1211/jpp/61.12.0012 · Source: PubMed
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.
    • "The present study clearly demonstrated that ICV-STZ produced memory impairment as indicated by the delay in escape latency and retention latency to find out the hidden platform in the Morris water maze task. We have also found that ICV-STZ showed a significant increase in acetylcholinesterase (AChE) activity suggesting cholinergic deficiency in the brain (Prakash and Kumar 2009). Furthermore, it has been reported that administration of STZ altered mRNA expression of AChE and α7 nicotinic acetylcholine receptor (α7 nAChR) in mice brain (Tota et al. 2011). "
    [Show abstract] [Hide abstract] ABSTRACT: Alzheimer’s disease (AD) is a neurodegenerative disease characterized by impaired memory function and oxidative damage. NO is a major signaling molecule produced in the central nervous system to modulate neurological activity through modulating nitric oxide synthase. Recently, PPAR-γ agonists have shown neuroprotective effects in neurodegenerative disorders. However, there have been only a few studies identifying mechanisms through which cognitive benefits may be exerted. The present study was designed to investigate the possible nitric oxide mechanism in the protective effect of pioglitazone against streptozotocin (STZ)-induced memory dysfunction. Wistar rats were intracerebroventricularly (ICV) injected with STZ. Then rats were treated with pioglitazone, NO modulators [l-arginine and nitro-l-arginine methyl ester (L-NAME)] for 21 days. Behavioral alterations were assessed in between the study period. Animals were sacrificed immediately after behavioral session, and mito-oxidative parameters, TNF-α, IL-6, and caspase-3 activity were measured. STZ-treated rats showed a memory deficit and significantly increased in mito-oxidative damage and inflammatory mediators and apoptosis in the hippocampus. Chronic treatment of pioglitazone significantly improved memory retention and attenuated mito-oxidative damage parameters, inflammatory markers, and apoptosis in STZ-treated rats. However, l-arginine pretreatment with lower dose of pioglitazone has not produced any protective effect as compared to per se. Furthermore, pretreatment of L-NAME significantly potentiated its protective effect, which indicates the involvement of nitric oxide for activation of PPAR-γ action. These results demonstrate that pioglitazone offers protection against STZ-induced memory dysfunction possibly due to its antioxidant, anti-inflammatory, and anti-apoptotic action mediating nitric oxide pathways and, therefore, could have a therapeutic potential in AD.
    Full-text · Article · Feb 2015
    Atish PrakashAtish PrakashAnil KumarAnil KumarLong Chiau Ming+1 more author ...Abu Bakar Abdul MajeedAbu Bakar Abdul Majeed
    • "Decreases of CAT activity, but unchanged SOD activity in the parietal cortex, putamen, amygdala, caudate nucleus and temporal cortex of patients with AD (Gsell et al. 1995) were found. In agreement, decreased CAT activity was found in the rat brain 3 weeks following the STZ-icv treatment (Khan et al. 2012; Misra et al. 2011; Tiwari et al. 2009; Veerendra Kumar and Gupta 2003; Prakash and Kumar 2009; Agrawal et al. 2009). In line with this, our results presented here demonstrate that CAT activity was regionally specifically decreased following the STZ-icv treatment (-60 % in HPC, -18 % in BS, -15 % in CB) with the HPC appearing more affected than BS and CB. "
    [Show abstract] [Hide abstract] ABSTRACT: Low intracerebroventricular (icv) doses of streptozotocin (STZ) produce regionally specific brain neurochemical changes in rats that are similar to those found in the brain of patients with sporadic Alzheimer's disease (sAD). Since oxidative stress is thought to be one of the major pathologic processes in sAD, catalase (CAT) activity was estimated in the regional brain tissue of animals treated intracerebroventricularly with STZ and the multitarget iron chelator, antioxidant and MAO-inhibitor M30 [5-(N-methyl-N-propargylaminomethyl)-8-hydroxyquinoline]. Five-day oral pre-treatment of adult male Wistar rats with 10 mg/kg/day M30 dose was followed by a single injection of STZ (1 mg/kg, icv). CAT activity was measured colorimetrically in the hippocampus (HPC), brain stem (BS) and cerebellum (CB) of the control, STZ-, M30- and STZ + M30-treated rats, respectively, 4 weeks after the STZ treatment. STZ-treated rats demonstrated significantly lower CAT activity in all three brain regions in comparison to the controls (p < 0.05 for BS and CB, p < 0.01 for HPC). M30 pre-treatment of the control rats did not influence the CAT activity in HPC and CB, but significantly increased it in BS (p < 0.05). M30 pre-treatment of STZ-treated rats significantly increased CAT activity in the HPC in comparison to the STZ treatment alone (p < 0.05) and normalized to the control values. These findings are in line with the assumption that reactive oxygen species contribute to the pathogenesis of STZ in a rat model of sAD and indicate that multifunctional iron chelators such as M30 might also have beneficial effects in this non-transgenic sAD model.
    Full-text · Article · Sep 2014
    • "Behavioral parameters 2.4.1. Assessment of cognitive performance (Morris water maze task) The acquisition and retention of memory was evaluated by using Morris water maze (Prakash and Kumar, 2009). Morris water maze consisted of large circular pool (150 cm in diameter, 45 cm in height, filled to a depth of 30 cm with water at 2871 1C). "
    [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.
    Full-text · Article · Jul 2014
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