Decreased nitric oxide markers and morphological changes in the brain of arsenic-exposed rats.
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 (10mg/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.
Ríos
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Departamento de Bioquímica, Facultad de Medicina, Universidad Autónoma de San Luis Potosí, Av. V. Carranza 2405, Col. Los Filtros, 78210 San Luis Potosí, S.L.P., Mexico.
Zarazúa
S
S
Santoyo
M E
ME
Sepúlveda-Saavedra
J
J
Romero-Díaz
V
V
Jiménez
V
V
Pérez-Severiano
F
F
Vidal-Cantú
G
G
Delgado
J M
JM
Jiménez-Capdeville
M E
ME
D000818:Animals; D018053:Arsenites / Q000633:toxicity*; D003342:Corpus Striatum / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D005260:Female; D005865:Gestational Age; D007608:Kainic Acid / Q000633:toxicity; D007774:Lactation; D015227:Lipid Peroxidation / Q000187:drug effects; D009566:Nitrates / Q000378:metabolism; D026602:Nitrergic Neurons / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D009573:Nitrites / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D017670:Sodium Compounds / Q000633:toxicity*; D014874:Water Pollutants, Chemical / Q000633:toxicity*
D018053:Arsenites; D018690:Excitatory Amino Acid Agonists; D009566:Nitrates; D009573:Nitrites; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D017670:Sodium Compounds; D014874:Water Pollutants, Chemical; D009569:Nitric Oxide; C017947:sodium arsenite; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D007608:Kainic Acid