Abnormal Expression of 8-Nitroguanine in the Brain of Mice Exposed to Arsenic Subchronically

Abstract

Arsenic (As) is a well-known carcinogen and a notorious health killer on the earth. The regional As toxicosis is becoming a global problem of public health. An anthropogenic source of arsenic exposure stems from the widespread use of arsenical drugs in food-animal production in the United States and China. This use results in residual contamination of food products from animals raised with the drugs, as well as environmental contamination associated with disposal of wastes from these animals 1) . Chronic exposure to As resulting in neurotoxicity to nervous system has been receiving more and more attention. The intelligence quotient (IQ) of children in As-rich region was found to be lower than that of children in low As area, and the difference was remarkable 2) . It was shown in animal experiments that As could pass through blood-brain barrier and invade the brain parenchyma, and there was a noticeable correlation between the extent of As exposure and the concentration of As in the brain of guinea pigs and rats 3) . Chaudhuri et al. discovered that even if the As concentration fell into the provisional guideline issued by World Health Organization's (WHO), As could impair the oxidation-reduction equilibrium, enhance the peroxidation level of cephalopin, decrease the glutathione concentration and render the brain tissue vulnerable Abstract: To provide molecular toxicological evidences for exploring the mechanism of arsenicinduced neurotoxicity the accumulation of arsenic (As), the formation of 8-nitroguanine (8-NO 2 -G) were examined in brain tissue of mice exposed to arsenic. And the gene expressions of inducible NOS (iNOS), superoxide dismutase 1 (SOD1) and peroxiredoxin 2 (Prdx2) were also analyzed by GeneChip. In the result, the concentration of As in the brain tissue of mice was 4.00, 13.70, 21.48 and 29.88 ng/g in the controls and experimental groups exposed to 1, 2 and 4 mg/l As 2 O 3 , respectively and increased in dose-response manner. Nervous cells in the brain of mice exposed to As showed disappearances of axons, vacuolar degeneration in cytoplasm and karyolysis, whereas no such pathological changes were observed in the control group. Weak immunoreactivity against 8-NO 2 -G was observed in the brain tissue of mice given 1 or 2 ppm arsenic trioxide. More intensive immunoreactivity was found in cells at 4 ppm and it was mainly distributed in cytoplasm. The expressions of SOD1 and Prdx2 were down-regulated in the brain of mice exposed to As, but iNOS expression was not disturbed by As exposure. No the 8-NO 2 -G immunoreactivity or abnormal expressions of these genes in brain tissue were observed in controls. These results indicate that As induces high expression of 8-NO 2 -G in brain tissues of mice and that RNA in the cells may be modified by overproduced reactive nitrogen species.

Low arsenic concentrations impair memory in rat offpring exposed during pregnancy and lactation: Role of α7 nicotinic receptor, glutamate and oxidative stress

“…targets of arsenic neurotoxicity and show myelin damage, disappearance of axons, vacuolar degeneration, and loss of cell-cell junction (Ma et al, 2010;Piao et al, 2011;Zarazua et al, 2010). Arsenic has been found to cause cholinergic dysfunctions associated with decreased activity of brain acetylcholinesterase and impaired learning and memory in experimental studies (Flora et al, 2009;Kopf et al, 2001;Nagaraja and Desiraju, 1994;Rodriguez et al, 2001;Wang et al, 2007).…”

Subchronic Arsenic Exposure Induces Anxiety-Like Behaviors in Normal Mice and Enhances Depression-Like Behaviors in the Chemically Induced Mouse Model of Depression

“…Recent animal studies suggest that neurons in the brain may be the major targets of arsenic neurotoxicity and show myelin damage, disappearance of axons, vacuolar degeneration, and loss of cell-cell junction. Arsenic exposure from drinking water containing 1-2 mg/L (approximately 0.1–0.2 mg/kg/day) has been shown to induce oxidative DNA damage in the brain [7–10]. While inorganic arsenic exposure has been correlated with impairments of new learning and recent memory, few studies have explored its effects on mood disorder such as anxiety and depression.…”

The History, Status, Gaps, and Future Directions of Neurotoxicology in China

“…Experimental studies showed that arsenic exposure produced hippocampal ultrastructural changes, down-regulation of NMDA receptor and postsynaptic signaling ( Luo et al 2012 ), and inhibited hippocampal neurogenesis ( Liu et al 2012 ). Arsenic also modulated DNA methylation and contributed to neural tube defects via epigenetic mechanisms ( Han et al 2011 ), promoted nitrative DNA lesions ( Piao et al 2011 ), and down-regulated mitochondrial succinate dehydrogenase subunit A ( Hong et al 2009 ) and Camk4 ( Wang et al 2009 ). Neuroglobin (Ngb) had a protective role in the cerebellum against arsenite-induced oxidative stress ( Wang J et al 2012 ).…”