title: Curcumin attenuates aluminum-induced oxidative stress and mitochondrial dysfunction in rat brain.
abstract: Aluminum is neurotoxic both in animals and human beings primarily because of its interference with biological enzymes in key mechanisms of metabolic pathways. Mitochondrial dysfunction is one such mechanism that has been implicated in the pathogenesis of neurodegenerative diseases like Alzheimer's disease. Aluminum toxicity is very closely related to Alzheimer's disease. We evaluated the potentials of curcumin, a known cytoprotectant, against neurotoxic consequences of aluminum that acts through a wide range of mechanisms. Curcumin has been reported to be an antioxidant, and it is this property that is widely held to be responsible for its protective effects in tissue. Aluminum was administered by oral gavage at a dose level of 100 mg/kg body wt/day for a period of 8 weeks. Curcumin was administered in conjunction with aluminum at a dose of 50 mg/kg of body wt i.p. for a period of 8 weeks on alternate days. The effects of different treatments were studied on oxidative phosphorylation and reduced glutathione of different regions of rat brain. The study indicates reduced activity of NADH dehydrogenase (complex I), succinic dehydrogenase (complex II), and cytochrome oxidize (Complex IV) in all the three regions of rat brain, i.e., cerebral cortex, mid brain, and cerebellum. Curcumin supplementation to aluminum-treated rats was able to normalize significantly the activities of all the three mitochondrial complexes as well as reduced glutathione content in all the three regions of brain which were altered following aluminum treatment. We conclude that curcumin, by attenuating oxidative stress, as evident by hypoxia in histological observations and mitochondrial dysfunction holds a promise as an agent that can potentially reduce aluminum-induced adverse effects in brain.
authors.affiliation: Department of Biophysics, Panjab University, Chandigarh, India 160014.
authors.forename: Pooja Khanna
authors.initials: PK
authors.lastname: Sood
authors.forename: Uma
authors.initials: U
authors.lastname: Nahar
authors.forename: Bimla
authors.initials: B
authors.lastname: Nehru
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000535:Aluminum / Q000633:toxicity*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000648:ultrastructure*; D003474:Curcumin / Q000494:pharmacology*; D003576:Electron Transport Complex IV / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D050884:HSP72 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology; D009245:NADH Dehydrogenase / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013385:Succinate Dehydrogenase / Q000378:metabolism; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D050884:HSP72 Heat-Shock Proteins; D012333:RNA, Messenger; D013778:Tetrazolium Salts; D013844:Thiazoles; D000255:Adenosine Triphosphate; D000535:Aluminum; D013385:Succinate Dehydrogenase; D009245:NADH Dehydrogenase; D003576:Electron Transport Complex IV; D000251:Adenosine Triphosphatases; C022616:thiazolyl blue; D005978:Glutathione; D003474:Curcumin