title: Quercetin attenuates neuronal death against aluminum-induced neurodegeneration in the rat hippocampus.
abstract: Aluminum is a light weight and toxic metal present ubiquitously on earth, which has gained considerable attention due to its neurotoxic effects. It also has been linked ecologically and epidemiologically to several neurological disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), Guamanian-Parkinsonian complex and Amyotrophic lateral sclerosis (ALS). The mechanism of aluminum neurotoxicity is poorly understood, but it is well documented that aluminum generates reactive oxygen species (ROS). Enhanced ROS production leads to disruption of cellular antioxidant defense systems and release of cytochrome c (cyt-c) from mitochondria to cytosol resulting in apoptotic cell death. Quercetin (a natural flavonoid) protects it from oxidative damage and has been shown to decrease mitochondrial damage in various animal models of oxidative stress. We hypothesized that if oxidative damage to mitochondria does play a significant role in aluminum-induced neurodegeneration, and then quercetin should ameliorate neuronal apoptosis. Administration of quercetin (10 mg/kg body wt/day) reduced aluminum (10 mg/kg body wt/day)-induced oxidative stress (decreased ROS production, increased mitochondrial superoxide dismutase (MnSOD) activity). In addition, quercetin also prevents aluminum-induced translocation of cyt-c, and up-regulates Bcl-2, down-regulates Bax, p53, caspase-3 activation and reduces DNA fragmentation. Quercetin also obstructs aluminum-induced neurodegenerative changes in aluminum-treated rats as seen by Hematoxylin and Eosin (H&E) staining. Further electron microscopic studies revealed that quercetin attenuates aluminum-induced mitochondrial swelling, loss of cristae and chromatin condensation. These results indicate that treatment with quercetin may represent a therapeutic strategy to attenuate the neuronal death against aluminum-induced neurodegeneration.
authors.affiliation: Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
authors.forename: D R
authors.initials: DR
authors.lastname: Sharma
authors.affiliation: Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
authors.forename: W Y
authors.initials: WY
authors.lastname: Wani
authors.affiliation: Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
authors.forename: A
authors.initials: A
authors.lastname: Sunkaria
authors.affiliation: Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
authors.forename: R J
authors.initials: RJ
authors.lastname: Kandimalla
authors.affiliation: Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
authors.forename: R K
authors.initials: RK
authors.lastname: Sharma
authors.affiliation: Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
authors.forename: D
authors.initials: D
authors.lastname: Verma
authors.affiliation: Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: A
authors.initials: A
authors.lastname: Bal
authors.affiliation: Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India. Electronic address: kdgill2002@yahoo.co.in.
authors.forename: K D
authors.initials: KD
authors.lastname: Gill
mesh_terms: D000535:Aluminum / Q000097:blood / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D002843:Chromatin / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011794:Quercetin / Q000494:pharmacology*; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D002843:Chromatin; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D045304:Cytochromes c; D011794:Quercetin; D000535:Aluminum; D013482:Superoxide Dismutase; C505410:Casp3 protein, rat; D053148:Caspase 3
keywords: aluminum; apoptosis; hippocampus; neurodegeneration; quercetin; reactive oxygen species