title: Sodium tungstate induced neurological alterations in rat brain regions and their response to antioxidants.
abstract: Tungsten, recognized recently as an environmental contaminant, is being used in arms and ammunitions as substitute to depleted uranium. We studied the effects of sodium tungstate on oxidative stress, few selected neurological variables like acetylcholinesterase, biogenic amines in rat brain regions (cerebral cortex, hippocampus and cerebellum) and their prevention following co-administration of N-acetylcysteine (NAC), naringenin and quercetin. Animals were sub-chronically exposed to sodium tungstate (100 ppm in drinking water) and orally co-supplemented with different antioxidants (0.30 mM) for three months. Sodium tungstate significantly decreased the activity of acetylcholinesterase, dopamine, nor-epinephrine and 5-hydroxytryptamine levels while it increased monoamine oxidase activity in different brain regions. Tungstate exposure produced a significant increase in biochemical variables indicative of oxidative stress while, neurological alterations were more pronounced in the cerebral cortex compared to other regions. Co-administration of NAC and flavonoids with sodium tungstate significantly restored glutathione, prevented changes in the brain biogenic amines, reactive oxygen species (ROS) and TBARS levels in the different brain regions. The protection was more prominent in the animals co-administered with NAC. We can thus conclude that sodium tungstate induced brain oxidative stress and the alterations in some neurological variables can effectively be reduced by co-supplementation of NAC.
authors.affiliation: Division of Regulatory Toxicology, Defence Research and Development Establishment, Gwalior, Madhya Pradesh, India.
authors.forename: Sherry
authors.initials: S
authors.lastname: Sachdeva
authors.affiliation: Division of Regulatory Toxicology, Defence Research and Development Establishment, Gwalior, Madhya Pradesh, India.
authors.forename: Satish C
authors.initials: SC
authors.lastname: Pant
authors.affiliation: Division of Regulatory Toxicology, Defence Research and Development Establishment, Gwalior, Madhya Pradesh, India.
authors.forename: Pramod
authors.initials: P
authors.lastname: Kushwaha
authors.affiliation: Division of Regulatory Toxicology, Defence Research and Development Establishment, Gwalior, Madhya Pradesh, India.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Bhargava
authors.affiliation: Division of Regulatory Toxicology, Defence Research and Development Establishment, Gwalior, Madhya Pradesh, India. Electronic address: sjsflora@drde.drdo.in.
authors.forename: Swaran J S
authors.initials: SJ
authors.lastname: Flora
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000111:Acetylcysteine / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D044950:Flavanones / Q000494:pharmacology; D005979:Glutathione Peroxidase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D017208:Rats, Wistar; D059550:Toxicity Tests, Subchronic / Q000379:methods; D017973:Tungsten Compounds / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D000975:Antioxidants; D044950:Flavanones; D018377:Neurotransmitter Agents; D017973:Tungsten Compounds; D005979:Glutathione Peroxidase; D008995:Monoamine Oxidase; D005982:Glutathione Transferase; D000110:Acetylcholinesterase; C005273:naringenin; C045951:tungstate; D004298:Dopamine; D000111:Acetylcysteine
keywords: Antioxidants; Brain regions; Flavonoids; Neurotoxicity; Oxidative stress; Sodium tungstate toxicity