title: Lead Intoxication Synergies of the Ethanol-Induced Toxic Responses in Neuronal Cells--PC12.
abstract: Lead (Pb)-induced neurodegeneration and its link with widespread neurobehavioral changes are well documented. Experimental evidences suggest that ethanol could enhance the absorption of metals in the body, and alcohol consumption may increase the susceptibility to metal intoxication in the brain. However, the underlying mechanism of ethanol action in affecting metal toxicity in brain cells is poorly understood. Thus, an attempt was made to investigate the modulatory effect of ethanol on Pb intoxication in PC12 cells, a rat pheochromocytoma. Cells were co-exposed to biological safe doses of Pb (10 μM) and ethanol (200 mM), and data were compared to the response of cells which received independent exposure to these chemicals at similar doses. Ethanol (200 mM) exposure significantly aggravated the Pb-induced alterations in the end points associated with oxidative stress and apoptosis. The finding confirms the involvement of reactive oxygen species (ROS)-mediated oxidative stress, and impairment of mitochondrial membrane potential, which subsequently facilitate the translocation of triggering proteins between cytoplasm and mitochondria. We further confirmed the apoptotic changes due to induction of mitochondria-mediated caspase cascade. These cellular changes were found to recover significantly, if the cells are exposed to N-acetyl cysteine (NAC), a known antioxidant. Our data suggest that ethanol may potentiate Pb-induced cellular damage in brain cells, but such damaging effects could be recovered by inhibition of ROS generation. These results open up further possibilities for the design of new therapeutics based on antioxidants to prevent neurodegeneration and associated health problems.
authors.affiliation: In Vitro Toxicology Laboratory, Indian Institute of Toxicology Research, P.O. Box: 80, MG Marg, Lucknow, 226001, UP, India.|Council of Scientific & Industrial Research, New Delhi, India.
authors.forename: V
authors.initials: V
authors.lastname: Kumar
authors.affiliation: In Vitro Toxicology Laboratory, Indian Institute of Toxicology Research, P.O. Box: 80, MG Marg, Lucknow, 226001, UP, India.|Council of Scientific & Industrial Research, New Delhi, India.
authors.forename: V K
authors.initials: VK
authors.lastname: Tripathi
authors.affiliation: In Vitro Toxicology Laboratory, Indian Institute of Toxicology Research, P.O. Box: 80, MG Marg, Lucknow, 226001, UP, India.|Council of Scientific & Industrial Research, New Delhi, India.
authors.forename: S
authors.initials: S
authors.lastname: Jahan
authors.affiliation: In Vitro Toxicology Laboratory, Indian Institute of Toxicology Research, P.O. Box: 80, MG Marg, Lucknow, 226001, UP, India.|Council of Scientific & Industrial Research, New Delhi, India.
authors.forename: M
authors.initials: M
authors.lastname: Agrawal
authors.affiliation: In Vitro Toxicology Laboratory, Indian Institute of Toxicology Research, P.O. Box: 80, MG Marg, Lucknow, 226001, UP, India.|Council of Scientific & Industrial Research, New Delhi, India.
authors.forename: A
authors.initials: A
authors.lastname: Pandey
authors.affiliation: In Vitro Toxicology Laboratory, Indian Institute of Toxicology Research, P.O. Box: 80, MG Marg, Lucknow, 226001, UP, India.|Council of Scientific & Industrial Research, New Delhi, India.
authors.forename: V K
authors.initials: VK
authors.lastname: Khanna
authors.affiliation: In Vitro Toxicology Laboratory, Indian Institute of Toxicology Research, P.O. Box: 80, MG Marg, Lucknow, 226001, UP, India. abpant@rediffmail.com.|Council of Scientific & Industrial Research, New Delhi, India. abpant@rediffmail.com.
authors.forename: A B
authors.initials: AB
authors.lastname: Pant
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D020013:Calcium Signaling / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D000431:Ethanol / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D007854:Lead / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells / Q000187:drug effects* / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins; D017382:Reactive Oxygen Species; D007854:Lead; D000431:Ethanol; D005978:Glutathione; D000111:Acetylcysteine
keywords: Ethanol; Neurotoxicity; PC12 cells; Pb