ABSTRACT
Lead toxicity is of major health concern due to its persistence in environment that induces cognitive impairment and neuronal degeneration. The present study was conducted to investigate the efficacy of quercetin, a ubiquitous bioflavonoid against lead-induced neurotoxicity in Wistar rats. Briefly, lead acetate (20mg/kg) was injected i.p., followed by oral administration of quercetin (50 and 100mg/kg) once daily for five consecutive days. On 6th day, rats were assessed for motor co-ordination, grip strength and sensorimotor impairment (by adhesive removal test). Lead treated rats have shown marked behavioral impairment with increased oxidative stress. Quercetin reduced lead-induced oxidative burden in brain, thus maintained the normal behavioral functions of lead-intoxicated rats. The lead administered group showed severely vacuolated and pyknotic nuclei with high expressions of Bak and Hsp-70. The expression of anti-apoptotic Bcl-2 was observed to be reduced in lead intoxicated group. Quercetin however, restored the normal morphology of brain and the expressions of Bak, Bcl-2 and Hsp-70. In conclusion, quercetin mitigates the toxic effect of lead effectively and thus, may be an important compound for developing effective therapeutic intervention against metal toxicity.
Subject(s)
HSP70 Heat-Shock Proteins/metabolism , Organometallic Compounds/toxicity , Oxidative Stress/drug effects , Quercetin/pharmacology , bcl-2 Homologous Antagonist-Killer Protein/metabolism , bcl-2-Associated X Protein/metabolism , Animals , Brain/drug effects , Brain/pathology , Cognition Disorders/drug therapy , Cognition Disorders/etiology , HSP70 Heat-Shock Proteins/genetics , Lead Poisoning/drug therapy , Lead Poisoning/etiology , Male , Rats , Rats, Wistar , Up-Regulation , bcl-2 Homologous Antagonist-Killer Protein/genetics , bcl-2-Associated X Protein/geneticsABSTRACT
Alzheimer's disease (AD) is a progressive neurodegenerative disorder resulting in cognitive decline and enhancement of oxidative loads in the brain. Flavonoids have been considered to exert human health benefits by anti-oxidant and anti-inflammatory properties. The present study is aimed to elucidate the neuroprotective effect of catechin hydrate (CH), a natural flavanoid with potential antioxidant and anti-inflammatory properties, on intracerebroventricular streptozotocin (ICV-STZ) induced neuronal loss and memory impairment. To test this hypothesis, male Wistar rats were pretreated with CH (10 and 20mg/kgb wt) orally once daily for 21 days and then bilaterally injected with ICV-STZ (3mg/kgb wt), while sham group rats receive the same volume of vehicle. After 2 weeks of ICV-STZ infusion, rats were tested for cognitive performance using Morris water maze (MWM) test and then sacrifice for biochemical and histopathological assays. CH was found to be successful in upregulating the antioxidant status and prevented the memory loss. The expression of choline acetyl transferase (ChAT) was decreased in ICV-STZ group and CH pretreatment increases the expression of ChAT. Moreover, inflammatory mediators like TNF-α, IL-1ß levels and expression of iNOS were significantly attenuated by CH pretreatment. The study suggests that CH is effective in preventing memory loss, ameliorating the oxidative stress and might be beneficial for the treatment of sporadic dementia of Alzheimer's type (SDAT).
Subject(s)
Alzheimer Disease/drug therapy , Catechin/therapeutic use , Cognition Disorders/drug therapy , Disease Models, Animal , Acetylcholinesterase/metabolism , Alzheimer Disease/pathology , Alzheimer Disease/psychology , Animals , Behavior, Animal , Choline O-Acetyltransferase/metabolism , Glutathione/metabolism , Hippocampus/enzymology , Hippocampus/metabolism , Interleukin-1beta/metabolism , Male , Maze Learning , Nitric Oxide Synthase Type II/metabolism , Rats , Rats, Wistar , Streptozocin , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Centella asiatica has been used as psychoactive and antioxidant herbal medicine since ancient time. The present study was design to evaluate the preventive role of ethanolic extract of C. asiatica in middle cerebral artery occlusion (MCAO) in rats. Male Wistar rats were gavaged orally with C. asiatica extract (100, 200 and 300 mg/kg body weight once daily) for 21 days and thereafter subjected to right MCAO for 2 h followed by 22-h reperfusion. Brain injury was evaluated by 2,3,5-triphenyltetrazolium chloride and hematoxylin and eosin staining. Behavioural outcomes as neurological deficit, rota rod test, and grip strength were assessed. In addition, lipid peroxidation, enzymatic and non enzymatic antioxidants were analyzed to assess the oxidative stress. Our results revealed that C. asiatica administration greatly improved neurobehavioral activity and diminished infarction volume along with the restored histological morphology of brain in MCAO rats. Furthermore, supplementation with this extract to MCAO group has reduced the level of thiobarbituric acid reactive species, restored glutathione content and augmented the activities of antioxidant enzymes-catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase and superoxide dismutase in a dose-dependent manner in ischemic rats. The remarkable antioxidant activity of C. asiatica may be attributed to its bioactive triterpenes, asiatic acid, asiaticoside, madecassic acid and madecosside and may be translated to clinical level for prevention of ischemic stroke.
