Effect of chronic treatment of carvedilol on oxidative stress in an intracerebroventricular streptozotocin induced model of dementia in rats.
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.
[show abstract] [hide abstract]
ABSTRACT: Better understanding of the effect of ageing on mitochondrial metabolism and of the mechanisms of action of various drugs is required to allow optimization of the treatment of many diseases with minimized risk of dangerous impairment of mitochondrial function. Numerous reports show that efficacy of medical treatment depends on the age of treated subjects. This applies particularly to the effect of drugs on various senescence-prone cellular pathways. In this review, we demonstrate how ageing affects various mitochondria-associated pathways and their response to a variety of factors. These factors include registered drugs and other chemicals, and account for diverse consequences which vary depending on the physiological condition. Pharmacological treatments aimed at improving mitochondrial function should thus have in mind the subject age.Current drug targets 01/2011; 12(6):827-49. · 3.93 Impact Factor