Decreased nitric oxide markers and morphological changes in the brain of arsenic-exposed rats

• Published in: Toxicology (Amsterdam) Vol. 261; no. 1; pp. 68 - 75
• Main Authors: Ríos, R, Zarazúa, S, Santoyo, M.E, Sepúlveda-Saavedra, J, Romero-Díaz, V, Jiménez, V, Pérez-Severiano, F, Vidal-Cantú, G, Delgado, J.M, Jiménez-Capdeville, M.E
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ireland Ltd 30.06.2009; Elsevier
• Subjects: Animals; Arsenic neurotoxicity; Arsenites - toxicity; Biological and medical sciences; Carcinogenesis, carcinogens and anticarcinogens; Chemical agents; Chemical and industrial products toxicology. Toxic occupational diseases; Corpus Striatum - drug effects; Corpus Striatum - enzymology; Corpus Striatum - pathology; Emergency; Excitatory Amino Acid Agonists - toxicity; Female; Gestational Age; Kainic Acid - toxicity; Lactation; Lipid Peroxidation - drug effects; Medical sciences; Metals and various inorganic compounds; Nitrates - metabolism; Nitrergic Neurons - drug effects; Nitrergic Neurons - enzymology; Nitrergic Neurons - pathology; Nitric oxide; Nitric Oxide - metabolism; Nitric oxide synthase; Nitric Oxide Synthase - metabolism; Nitric Oxide Synthase Type I; Nitrites - metabolism; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar; Reactive Oxygen Species - metabolism; RNA, Messenger - metabolism; Sodium Compounds - toxicity; Toxicology; Tumors; Water Pollutants, Chemical - toxicity; Nitric oxide synthase; Arsenic neurotoxicity; Nitric oxide; Nervous system diseases; Arsenic; Rat; Enzyme; Toxicity; Rodentia; Central nervous system; Biological marker; Nitric-oxide synthase; Encephalon; Carcinogen; Vertebrata; Neurotoxicity; Mammalia; Animal; Morphological change; Oxidoreductases
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/j.tox.2009.04.055

Abstract Epidemiological studies demonstrate an association between chronic consumption of arsenic contaminated water and cognitive deficits, especially when the exposure takes place during childhood. This study documents structural changes and nitrergic deficits in the striatum of adult female Wistar rats exposed to arsenic in drinking water (3 ppm, approximately 0.4 mg/kg per day) from gestation, throughout lactation and development until the age of 4 months. Kainic acid injected animals (10 mg/kg, i.p.) were also analyzed as positive controls of neural cell damage. Morphological characteristics of cells, fiber tracts and axons were analyzed by means of light microscopy as well as immunoreactivity to neuronal nitric oxide synthase (nNOS). As nitrergic markers, nitrite/nitrate concentrations, nNOS levels and expression of nNOS-mRNA were quantified in striatal tissue. Reactive oxygen species (ROS) and lipid peroxidation (LPx) were determined as oxidative stress markers. Arsenic exposure resulted in moderate to severe alterations of thickness, organization, surrounding space and shape of fiber tracts and axons, while cell bodies remained healthy. These anomalies were not accompanied by ROS and/or LPx increases. By contrast, except the expression of nNOS-mRNA, all nitrergic markers including striatal nNOS immunoreactivity presented a significant decrease. These results indicate that arsenic targets the central nitrergic system and disturbs brain structural organization at low exposure levels.