Oxidative DNA Damage in Relation to Neurotoxicity in the Brain of Mice Exposed to Arsenic at Environmentally Relevant Levels (original) (raw)
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Effect of high arsenic content in drinking water on rat brain
Indian journal of biochemistry & biophysics, 1999
The permissible limit of arsenic content in drinking water is 0.05 ppm, whereas, in many parts of West Bengal the arsenic level in drinking water is 0.1 ppm, frequently 0.3 ppm and even 3.0 ppm, though rarely. In order to assess possible risk to brain function by drinking such water, rats were given arsenic mixed in drinking water at the above four concentrations for 40 days. There was increased lipid peroxidation at all doses of arsenic, including the 'permissible limit', decrease in glutathione level, superoxide dismutase and glutathione reductase activities, indicating the free-radical-mediated degeneration of brain.
ABSTRACT: Neurotoxicity by drinking well water contaminated with arsenic (As) or accidentally exposed to As compounds has been described in adults and infants by previous studies. Biomethylation of As generates toxic metabolites that could help explain the adverse effects observed following As exposure in human and in animal models. Here dose related accumulation of methylated As metabolites in mouse brain are studied and show that brain metabolizes arsenite to monomethyl arsonic acid (MMA) and dimethyl arsinic acid (DMA), being DMA the main metabolite in this tissue. Glutathione reductase activity was inhibited at the highest dose tested in liver and brain.
Neurotoxicology and Teratology, 2010
Several studies have associated chronic arsenicism with decreases in IQ and sensory and motor alterations in humans. Likewise, studies of rodents exposed to inorganic arsenic ( i As) have found changes in locomotor activity, brain neurochemistry, behavioral tasks, oxidative stress, and in sensory and motor nerves. In the current study, male Sprague-Dawley rats were exposed to environmentally relevant doses of i As (0.05, 0.5 mg i As/L) and to a high dose (50 mg i As/L) in drinking water for one year. Hypoactivity and increases in the striatal dopamine content were found in the group treated with 50 mg i As/L. Exposure to 0.5 and 50 mg i As/L increased the total brain content of As. Furthermore, i As exposure produced a dose-dependent upregulation of mRNA for Mn-SOD and Trx-1 and a down-regulation of DAR-D 2 mRNA levels in the nucleus accumbens. DAR-D 1 and Nrf2 mRNA expression were down-regulated in nucleus accumbens in the group exposed to 50 mg i As/L. Trx-1 mRNA levels were up-regulated in the cortex in an i As dose-dependent manner, while DAR-D 1 mRNA expression was increased in striatum in the 0.5 mg i As/L group. These results show that chronic exposure to low levels of arsenic causes subtle but region-specific changes in the nervous system, especially in antioxidant systems and dopaminergic elements. These changes became behaviorally evident only in the group exposed to 50 mg i As/L. i As in a brain region-specific manner following the order cortexN striatum N hippocampus N hypothalamus N cerebellum, in comparison to a non-exposed control group .
Arsenic Toxicity and Neurobehaviors: A Review
Deterioration in public health due to arsenic toxicity is a worldwide concern for clinicians. The subject requires extensive and careful assessment of arsenic toxicity born symptoms, across the geographical boundaries. Arsenic induced deleterious effects have been documented in countries, including India, Bangladesh, Argentina, Australia, China, Hungary, Thailand, Mexico and United States of America, which cover the major part of world population. Arsenic found in soil and drinking water comes from geophysical as well as anthropogenic sources. Humans are exposed to arsenic through food, drinking water and or smelters. Nevertheless, newborns are most sensitive to arsenic insult and if mother is exposed to arsenic at gestational stage, irreversible postnatal cardiac, carcinogenic, behavioral, cognitive and motor disabilities are inevitable. Sufficient data from animal studies on hamsters, mice, rats and rabbits demonstrate arsenic to produce developmental toxicity, which includes malf...
Oncotarget, 2017
Through contaminated diet, water, and other forms of environmental exposure, arsenic affects human health. There are many U.S. and worldwide "hot spots" where the arsenic level in public water exceeds the maximum exposure limit. The biological effects of chronic arsenic exposure include generation of reactive oxygen species (ROS), leading to oxidative stress and DNA damage, epigenetic DNA modification, induction of genomic instability, and inflammation and immunomodulation, all of which can initiate carcinogenesis. High arsenic exposure is epidemiologically associated with skin, lung, bladder, liver, kidney and pancreatic cancer, and cardiovascular, neuronal, and other diseases. This review briefly summarizes the biological effects of arsenic exposure and epidemiological cancer studies worldwide, and provides an overview for emerging rodent-based studies of reagents that can ameliorate the effects of arsenic exposure in vivo. These reagents may be translated to human populations for disease prevention. We propose the importance of developing a biomarker-based precision prevention approach for the health issues associated with arsenic exposure that affects millions of people worldwide.
Arsenic-induced biochemical and genotoxic effects and distribution in tissues of Sprague–Dawley rats
Microchemical Journal, 2012
a b s t r a c t Arsenic (As) is a well documented human carcinogen. However, its mechanisms of toxic action and carcinogenic potential in animals have not been conclusive. In this research, we investigated the biochemical and genotoxic effects of As and studied its distribution in selected tissues of Sprague-Dawley rats. Four groups of six male rats, each weighing approximately 60 ± 2 g, were injected intraperitoneally, once a day for 5 days with doses of 5, 10, 15, 20 mg/kg BW of arsenic trioxide. A control group was also made of 6 animals injected with distilled water. Following anaesthetization, blood was collected and enzyme analysis was performed by spectrophotometry following standard protocols. At the end of experimentation, the animals were sacrificed, and the lung, liver, brain and kidney were collected 24 h after the fifth day treatment. Chromosome and micronuclei preparation was obtained from bone marrow cells. Arsenic exposure significantly increased (p b 0.05) the activities of plasma alanine aminotransferase-glutamate pyruvate transaminase (ALT/GPT), and aspartate aminotransferase-glutamate oxaloacetate transaminase (AST/GOT), as well as the number of structural chromosomal aberrations (SCA) and frequency of micronuclei (MN) in the bone marrow cells. In contrast, the mitotic index in these cells was significantly reduced (p b 0.05). These findings indicate that aminotransferases are candidate biomarkers for arsenic-induced hepatotoxicity. Our results also demonstrate that As has a strong genotoxic potential, as measured by the bone marrow SCA and MN tests in Sprague-Dawley rats. Total arsenic concentrations in tissues were measured by inductively coupled plasma mass spectrometry (ICP-MS). A dynamic reaction cell (DRC) with hydrogen gas was used to eliminate the ArCl interference at mass 75, in the measurement of total As. Total As doses in tissues tended to correlate with specific exposure levels.
In vivo evaluation of arsenic-associated behavioral and biochemical alterations in F0 and F1 mice
Chemosphere, 2020
h i g h l i g h t s Arsenic induces neurobehavioral and biochemical alterations in both F 0 and F 1 mice. Effects of arsenic are more pronounced in arsenic-exposed F 1 mice than F 0. Accumulation of arsenic is higher in the liver, brain, and kidney of F 1 mice. Arsenic markedly increases arsenic-associated tissue damages in the liver and kidney of F 1 mice. Arsenic-exposed offspring mice are more vulnerable to arsenic exposure.
The effects of arsenic exposure on the nervous system
Toxicology letters, 2003
Arsenic (As) is a common environmental contaminant widely distributed around the world. Human exposure to this metalloid comes from well water and contaminated soil, from fish and other sea organisms rich in methylated arsenic species, and from occupational exposure.
Developmental Neurotoxicity of Arsenic: Involvement of Oxidative Stress and Mitochondrial Functions
Biological trace element research, 2018
Over the last decade, there has been an increased concern about the health risks from exposure to arsenic at low doses, because of their neurotoxic effects on the developing brain. The exact mechanism underlying arsenic-induced neurotoxicity during sensitive periods of brain development remains unclear, although enhanced oxidative stresses, leading to mitochondrial dysfunctions might be involved. Here, we highlight the generation of reactive oxygen species (ROS) and oxidative stress which leads to mitochondrial dysfunctions and apoptosis in arsenic-induced developmental neurotoxicity. Here, the administration of sodium arsenite at doses of 2 or 4 mg/kg body weight in female rats from gestational to lactational (GD6-PD21) resulted to increased ROS, led to oxidative stress, and increased the apoptosis in the frontal cortex, hippocampus, and corpus striatum of developing rats on PD22, compared to controls. Enhanced levels of ROS were associated with decreased mitochondrial membrane pot...
Arsenic-Induced Genotoxicity and Genetic Susceptibility to Arsenic-Related Pathologies
International Journal of Environmental Research and Public Health, 2013
The arsenic (As) exposure represents an important problem in many parts of the World. Indeed, it is estimated that over 100 million individuals are exposed to arsenic, mainly through a contamination of groundwaters. Chronic exposure to As is associated with adverse effects on human health such as cancers, cardiovascular diseases, neurological diseases and the rate of morbidity and mortality in populations exposed is alarming. The purpose of this review is to summarize the genotoxic effects of As in the cells as well as to discuss the importance of signaling and repair of arsenic-induced DNA damage. The current knowledge of specific polymorphisms in candidate genes that confer susceptibility to arsenic exposure is also reviewed. We also discuss the perspectives offered by the determination of biological markers of early effect on health, incorporating genetic polymorphisms, with biomarkers for exposure to better evaluate exposure-response clinical relationships as well as to develop novel preventative strategies for arsenic-health effects.