ABSTRACT
ABSTRACT: Arsenic compounds are colorless and odorless and toxicity can occur either acutely following ingestion of arsenicals with gastrointestinal disturbances or due to chronic exposure usually presenting with dermatologic lesions and peripheral neuropathy. We report a young couple who presented with signs and symptoms of painful sensorimotor peripheral neuropathy in a typical "stocking and glove" pattern. They had raised urinary arsenic levels with normal blood levels and thus, a diagnosis of chronic arsenic poisoning due to contaminated water intake was made after detecting elevated arsenic levels in their home water supply. Both patients underwent chelation therapy with dimercaprol for 14 days and reported subjective and objective improvement in symptoms with the reduction in urinary arsenic levels at the end of therapy.
Subject(s)
Arsenic Poisoning , Peripheral Nervous System Diseases , Humans , Arsenic/urine , Arsenic Poisoning/complications , Chelating Agents/therapeutic use , Chelation Therapy , Chronic Disease , Dimercaprol/therapeutic use , Peripheral Nervous System Diseases/chemically induced , Treatment OutcomeABSTRACT
Inorganic trivalent arsenic (iAsâ ¢) at environmentally relevant levels has been found to cause developmental toxicity. Maternal exposure to iAsâ ¢ leads to enduring hepatic lipid deposition in later adult life. However, the exact mechanism in iAsâ ¢ induced hepatic developmental hazards is still unclear. In this study, we initially found that gestational exposure to iAsâ ¢ at an environmentally relevant concentration disturbs lipid metabolism and reduces levels of alpha-ketoglutaric acid (α-KG), an important mitochondrial metabolite during the citric acid cycle, in fetal livers. Further, gestational supplementation of α-KG alleviated hepatic lipid deposition caused by early-life exposure to iAsâ ¢. This beneficial effect was particularly pronounced in female offspring. α-KG partially restored the ß-oxidation process in hepatic tissues by hydroxymethylation modifications of carnitine palmitoyltransferase 1a (Cpt1a) gene during fetal development. Insufficient ß-oxidation capacities probably play a crucial role in hepatic lipid deposition in adulthood following in utero arsenite exposure, which can be efficiently counterbalanced by replenishing α-KG. These results suggest that gestational administration of α-KG can ameliorate hepatic lipid deposition caused by iAsâ ¢ in female adult offspring partially through epigenetic reprogramming of the ß-oxidation pathway. Furthermore, α-KG shows potential as an interventive target to mitigate the harmful effects of arsenic-induced hepatic developmental toxicity.
Subject(s)
Arsenic Poisoning , Arsenic , Arsenicals , Humans , Adult , Female , Arsenic/toxicity , Arsenic/metabolism , Ketoglutaric Acids/metabolism , Ketoglutaric Acids/pharmacology , Arsenicals/metabolism , Arsenic Poisoning/metabolism , Liver , Dietary Supplements , Epigenesis, Genetic , LipidsABSTRACT
For the potential health benefits and nutritional value, polyphenols are one of the secondary metabolites of plants that have received extensive research. It has anti-inflammatory and cytotoxicity-reducing properties in addition to a high antioxidant content. Macromolecular polyphenols and polysaccharides are biologically active natural polymers with antioxidant and anti-inflammatory potential. Arsenic is an ecologically toxic metalloid. Arsenic in drinking water is the most common way people come into contact with this metalloid. While arsenic is known to cause cancer, it is also used to treat acute promyelocytic leukemia (APL). The treatment's effectiveness is hampered by the adverse effects it can cause on the body. Oxidative stress, inflammation, and the inability to regulate cell death cause the most adverse effects. Polyphenols and other macromolecules like polysaccharides act as neuroprotectants by mitigating free radical damage, inhibiting nitric oxide (NO) production, lowering A42 fibril formation, boosting antioxidant levels, and controlling apoptosis and inflammation. To prevent the harmful effects of toxins, polyphenols and pectin lower oxidative stress, boost antioxidant levels, improve mitochondrial function, control apoptosis, and suppress inflammation. Therefore, it prevents damage to the heart, liver, kidneys, and reproductive system. This review aims to identify the effects of the polyphenols in conjugation with polysaccharides as an ameliorative strategy for arsenic-induced toxicity in various organs.
Subject(s)
Arsenic Poisoning , Arsenic , Selenium , Humans , Antioxidants/pharmacology , Selenium/pharmacology , Arsenic/pharmacology , Copper/pharmacology , Arsenic Poisoning/prevention & control , Polyphenols/pharmacology , Zinc/pharmacology , Oxidative Stress , Inflammation , Pectins/pharmacology , Anti-Inflammatory Agents/pharmacologyABSTRACT
Arsenic (As) is a highly toxic heavy metal and has been widely concerned for its hazardous environmental impact. Aromatic organic arsenic (AOCs) has been frequently used as an animal supplement to enhance feed utilization and prevent dysentery. The majority of organic arsenic could be discharged from the body and evolve as highly toxic inorganic arsenic that is hazardous to the environment and human health via biological conversion, photodegradation, and photo-oxidation. Current environmental issues necessitate the development and application of multifunctional porous materials in environmental remediation. Compared to the conventional adsorbent, such as activated carbon and zeolite, metal-organic frameworks (MOFs) exhibit a number of advantages, including simple synthesis, wide variety, simple modulation of pore size, large specific surface area, excellent chemical stability, and easy modification. In recent years, numerous scientists have investigated MOFs related materials involved with organic arsenic. These studies can be divided into three categories: detection of organic arsenic by MOFs, adsorption to remove organic arsenic by MOFs, and catalytic removal of organic arsenic by MOFs. Here, we conduct a critical analysis of current research findings and knowledge pertaining to the structural characteristics, application methods, removal properties, interaction mechanisms, and spectral analysis of MOFs. We summarized the application of MOFs in organic arsenic detection, adsorption, and catalytic degradation. Other arsenic removal technologies and conventional substances are also being investigated. This review will provide relevant scientific researchers with references.
Subject(s)
Arsenic Poisoning , Arsenic , Metal-Organic Frameworks , Humans , Metal-Organic Frameworks/chemistry , Heavy Metal Poisoning , AdsorptionABSTRACT
Due to structural racism and income inequality, exposure to environmental chemicals is tightly linked to socioeconomic factors. In addition, exposure to psychosocial stressors, such as racial discrimination, as well as having limited resources, can increase susceptibility to environmentally induced disease. Yet, studies are often conducted separately in fields of social science and environmental science, reducing the potential for holistic risk estimates. To tackle this gap, we developed the Chemical and Social Stressors Integration Technique (CASS-IT) to integrate environmental chemical and social stressor datasets. The CASS-IT provides a framework to identify distinct geographic areas based on combinations of environmental chemical exposure, social vulnerability, and access to resources. It incorporates two data dimension reduction tools: k-means clustering and latent profile analysis. Here, the CASS-IT was applied to North Carolina (NC) as a case study. Environmental chemical data included toxic metals - arsenic, manganese, and lead - in private drinking well water. Social stressor data were captured by the CDC's social vulnerability index's four domains: socioeconomic status, household composition and disability, minority status and language, and housing type and transportation. Data on resources were derived from Federal Emergency Management Agency (FEMA's) Resilience and Analysis Planning Tool, which generated measures of health resources, social resources, and information resources. The results highlighted 31 NC counties where exposure to both toxic metals and social stressors are elevated, and health resources are minimal; these are counties in which environmental justice is of utmost concern. A census-tract level analysis was also conducted to demonstrate the utility of CASS-IT at different geographical scales. The tract-level analysis highlighted specific tracts within counties of concern that are particularly high priority. In future research, the CASS-IT can be used to analyze United States-wide environmental datasets providing guidance for targeted public health interventions and reducing environmental disparities.
Subject(s)
Arsenic Poisoning , Drinking Water , United States , Humans , North Carolina , Public Health , Environmental Exposure , Heavy Metal PoisoningABSTRACT
Arsenic (As) is a toxic metalloid that affects many organs through drinking water. This study aims to examine the efficacy of ozone therapy on chronic arsenic toxicity. Twenty-four male Wistar albino rats were housed in individual cages and grouped as control, As, O3, and As + O3. As was applied by adding 5 mg/kg/day in drinking water for 60 days. Ozone therapy was applied at 0.5 mg/kg/day (i.p.) O3 in the last 5 days of the experimental period. Tissues were harvested and analyzed for histopathological injury and apoptotic markers. There was no significant difference between the As + O3 and O3 groups (p = 0.186 and p = 0.599) for light microscopic criteria: inflammatory cell infiltration and hydropic degeneration in liver tissue.In TUNEL assessments, similar outcomes were obtained in the control and As + O3 groups. A statistically significant increase was observed in p53 and Caspase 3 (Casp-3) expression levels in the As group compared to the O3 and As + O3 groups. There was no significant difference between the As + O3 and O3 groups on peritubular hemorrhage and desquamation parameters in kidneys (p = 0.147 and p = 0.094). The KIM-1 expression level was significantly increased in the As group compared to the As + O3 group (p = 0.01), and the Casp-3 expression level was not significantly changed in the O3 group compared to the As + O3 group (p = 0.59). In conclusion, it is determined that ozone therapy has ameliorative effects on the microscopic injury of liver and kidney tissues. In addition to microscopic improvement, KIM-1 gene expression levels were ameliorated in the kidneys. The apoptotic cell counts and the Casp-3 and p53 gene expression levels were decreased by O3 administration. Thus, ozone therapy can be a treatment choice for As toxicity.
Subject(s)
Arsenic Poisoning , Arsenic , Drinking Water , Ozone , Rats , Male , Animals , Rats, Wistar , Ozone/pharmacology , Arsenic/toxicity , Tumor Suppressor Protein p53ABSTRACT
Arsenic can be specifically enriched by rice, and the health hazards caused by high arsenic rice are gradually attracting attention. This study aimed to explore the potential of microbial detoxification via gut microbiome in the treatment of sub-chronic arsenic poisoning. We first exposed mice to high-dose arsenic feed (30 mg/kg, rice arsenic composition) for 60 days to promote arsenic-induced microbes in situ in the gastrointestinal tract, then transplanted their fecal microbiota (FMT) into another batch of healthy recipient mice, and dynamically monitored the microbial colonization by 16S rRNA sequencing and ITS sequencing. The results showed that in situ arsenic-induced fecal microbiome can stably colonized and interact with indigenous microbes in the recipient mice in two weeks, and established a more stable network of gut microbiome. Then, the recipient mice continued to receive high-dose arsenic exposure for 52 days. After above sub-chronic arsenic exposure, compared with the non-FMT group, fecal arsenic excretion, liver and plasma arsenic accumulation were significantly lower (P < 0.05), and that in kidney, hair, and thighbone present no significant differences. Metabolomics of feces- plasma-brain axis were also disturbed, some up-regulated metabolites in feces, plasma, and cerebral cortex may play positive roles for the host. Therefore, microbial detoxification has potential in the treatment of sub-chronic arsenic poisoning. However, gut flora is an extremely complex community with different microorganisms have different arsenic metabolizing abilities, and various microbial metabolites. Coupled with the matrix effects, these factors will have various effects on the efflux and accumulation of arsenic. The definite effects (detoxification or non-detoxification) could be not assured based on the current study, and more systematic and rigorous studies are needed in the future.
Subject(s)
Arsenic Poisoning , Arsenic , Mice , Animals , Fecal Microbiota Transplantation , Arsenic/toxicity , RNA, Ribosomal, 16S/genetics , FecesABSTRACT
Studies have demonstrated that arsenic (As) induces male reproductive injury, however, the mechanism remains unknown. The high levels of arsenic (3) methyltransferase (As3MT) promote As-induced male reproductive toxicity. For As-exposed mice, the germ cells in seminiferous tubules and sperm quality were reduced. Exposure to As caused lower S-adenosylmethionine (SAM) and 5-methylcytosine (5 mC) levels, histone and DNA hypomethylation, upregulation of long interspersed element class 1 (LINE1, or L1), defective repair of double-strand breaks (DSBs), and the arrest of meiosis, resulting in apoptosis of germ cells and lower litter size. For GC-2spd (GC-2) cells, As induced apoptosis, which was prevented by adding SAM or by reducing the expression of As3MT. The levels of LINE1, affected by SAM content, were involved in As-induced apoptosis. Furthermore, folic acid (FA) and vitamin B12 (VB12) supplements restored SAM, 5 mC, and LINE1 levels and blocked impairment of spermatogenesis and testes and lower litter size. Exposed to As, mice with As3MT knockdown showed less impairment of spermatogenesis and testes and greater litter size compared to As-exposed wild-type (WT) mice. Thus, the high As3MT levels induced by As consume SAM and block histone and LINE1 DNA methylation, elevating LINE1 expression and evoking impairment of spermatogenesis, which causes male reproductive damage. Overall, we have found a mechanism for As-induced male reproductive damage, which provides biological insights into the alleviation of reproductive injury induced by environmental factors.
Subject(s)
Arsenic Poisoning , Arsenic , 5-Methylcytosine , Animals , Arsenic/metabolism , Arsenic/toxicity , DNA/metabolism , DNA Methylation , Folic Acid , Histones/metabolism , Male , Methyltransferases/metabolism , Mice , S-Adenosylmethionine/metabolism , Semen/metabolism , Vitamin B 12ABSTRACT
Chronic arsenic (As) poisoning is mostly due to subsoil water contaminated with As and its salts. Exposure to As has been found to cause an elevation in reactive oxygen species (ROS), leading to the damage of DNA and proteins, and it also causes immunotoxicity. Treatment regimens are primarily based on chelation therapy and amino acid and vitamin supplementations. Recent studies have established that natural products display effective and progressive relief from arsenicosis without any side effects. ß-glucogallin (BGG), a gallo-tannin natural product, is reported to possess anti-oxidant and anti-inflammatory properties. In the present study, we aim to observe the protective role of BGG against As-induced cytotoxicity, apoptosis, mitochondrial dysfunction, and the underlying mechanisms in RAW 264.7 macrophage cells. We found that BGG alleviates As-induced ROS, apoptosis, and mitochondrial dysfunction in RAW 264.7 macrophage cells. Thus, BGG can be used therapeutically to prevent As-induced toxicity.
Subject(s)
Arsenic Poisoning , Arsenic , Animals , Apoptosis , Arsenic/toxicity , Arsenic Poisoning/metabolism , Arsenic Poisoning/prevention & control , Arsenic Trioxide/pharmacology , Hydrolyzable Tannins/pharmacology , Mice , NF-kappa B/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Oxidative Stress , Oxides/toxicity , RAW 264.7 Cells , Reactive Oxygen Species/metabolismABSTRACT
Chronic exposure to arsenic (As) compounds leads to its accumulation in the body, with skin lesions and cancer being the most typical outcomes. Treating As-induced diseases continues to be challenging as there is no specific, safe, and efficacious therapeutic management. Therapeutic and preventive measures available to combat As toxicity refer to chelation therapy, antioxidant therapy, and the intake of natural dietary compounds. Although chelation therapy is the most commonly used method for detoxifying As, it has several side effects resulting in various toxicities such as hepatotoxicity, neurotoxicity, and other adverse consequences. Drugs of plant origin and natural dietary compounds show efficient and progressive relief from As-mediated toxicity without any particular side effects. These natural compounds have also been found to aid the elimination of As from the body and, therefore, can be more effective than conventional therapeutic agents in ameliorating As toxicity. This review provides an overview of the recently updated knowledge on treating As poisoning through natural dietary compounds. This updated information may serve as a basis for defining novel prophylactic and therapeutic formulations.
Subject(s)
Arsenic Poisoning , Arsenic , Arsenicals , Antioxidants/pharmacology , Antioxidants/therapeutic use , Arsenic/toxicity , Arsenic Poisoning/drug therapy , Humans , Plant Extracts/therapeutic useABSTRACT
Increasing evidence supports the role of arsenic in dysregulated immune and inflammation responses, while, safe and effective treatments have not been fully examined. Rosa roxburghii Tratt (RRT), a traditional Chinese edible fruit with potential immunoregulatory activities, was considered as a dietary supplement to explore its protective effects and possible mechanism in arsenic-induced dysregulated inflammation responses. We enrolled 209 arsenicosis patients and 41 controls to obtain baseline data, including the degree of arsenic poisoning prior to the RRT juice (RRTJ) intervention. Then, based on criteria of inclusion and exclusion and the principle of voluntary participation, 106 arsenicosis patients who volunteered to receive treatment were divided into RRTJ (n = 53) and placebo (n = 53) groups randomly. After three months follow-up, 89 subjects (46 and 43 of the RRTJ and placebo groups, respectively) completed the study and were examined for the effects and possible mechanisms of RRTJ on the Th17 cells-related pro-inflammatory responses in peripheral blood mononuclear cells (PBMCs). The PBMCs had higher levels of Th17 and Th17-related inflammatory cytokines IL-17, IL-6, and RORγt. Furthermore, the gene expressions of STAT3 and SOCS3 in PBMCs increased and decreased, respectively. Conversely, RRTJ decreased the number of Th17 cells, secretion of IL-17, IL-6, RORγt, and relative mRNA levels of STAT3, and increased the transcript levels of SOCS3. This study provides limited evidence that possible immunomodulatory effects of RRTJ on the critical regulators, IL-6 and STAT3, of the Th17 cells in arsenicosis patients, which indicated that IL-6/STAT3 pathway might appear as a potential therapeutic target in arsenicosis.
Subject(s)
Arsenic Poisoning , Arsenic , Phytotherapy , Plant Preparations , Rosa , Arsenic/toxicity , Arsenic Poisoning/genetics , Arsenic Poisoning/metabolism , Arsenic Poisoning/therapy , Fruit and Vegetable Juices , Humans , Inflammation/chemically induced , Interleukin-17/metabolism , Interleukin-6 , Leukocytes, Mononuclear/metabolism , Nuclear Receptor Subfamily 1, Group F, Member 3 , Plant Preparations/metabolism , Plant Preparations/therapeutic use , Rosa/metabolismABSTRACT
Arsenic, a metalloid, is known to cause deleterious effects in various body organs, particularly the liver, urinary bladder, and brain, and these effects are primarily mediated through oxidative stress. Chelation therapy has been considered one of the promising medical treatments for arsenic poisoning. Meso 2,3- dimercaptosuccinic acid (DMSA) has been recognized as one of the most effective chelating drugs to treat arsenic poisoning. However, the drug is compromised with a number of shortcomings, including the inability to treat chronic arsenic poisoning due to its extracellular distribution. Monoisoamyl 2,3-dimercaptosuccinic acid, one of the analogues of meso 2,3-dimeraptosuccinic acid (DMSA), is a lipophilic chelator and has shown promise to be considered as a potential future chelating agent/antidote not only for arsenic but also for a few other heavy metals like lead, mercury, cadmium, and gallium arsenide. The results from numerous studies carried out in the recent past, mainly from our group, strongly support the clinical application of MiADMSA. This review paper summarizes most of the scientific details including the chemistry, pharmacology, and safety profile of MiADMSA. The efficacy of MiADMSA mainly against arsenic toxicity but also a few other heavy metals was also discussed. We also reviewed a few other strategies in order to achieve the optimum effects of MiADMSA, like combination therapy using two chelating agents or coadministration of a natural and synthetic antioxidant (including phytomedicine) along with MiADMSA for treatment of metal/metalloid poisoning. We also briefly discussed the use of nanotechnology (nano form of MiADMSA i.e. nano-MiADMSA) and compared it with bulk MiADMSA. All these strategies have been shown to be beneficial in getting more pronounced therapeutic efficacy of MiADMSA, as an adjuvant or as a complementary agent, by significantly increasing the chelating efficacy of MiADMSA.
Subject(s)
Arsenic Poisoning , Arsenic , Mercury , Animals , Antidotes , Antioxidants/therapeutic use , Arsenic Poisoning/drug therapy , Cadmium , Chelating Agents/pharmacology , Chelating Agents/therapeutic use , Heavy Metal Poisoning/drug therapy , Rats , Rats, Wistar , Succimer/analogs & derivatives , Succimer/pharmacology , Succimer/therapeutic useABSTRACT
Arsenic toxicity is a major concern due to its deleterious consequences for human health. Rapid industrialization also has weakened the quality of the environment by introducing pollutants that may disrupt balanced ecosystems, adversely and irreversibly impacting humans, plants, and animals. Arsenic, an important toxicant among all environmental hazards, can lead to several detrimental effects on cells and organs, impacting the overall quality of life. Nevertheless, arsenic also has a rich history as a chemotherapeutic agent used in ancient days for the treatment of diseases such as malaria, cancer, plague, and syphilis when other chemotherapeutic agents were yet to be discovered. Arsenicosis-mediated disorders remain a serious problem due to the lack of effective therapeutic options. Initially, chelation therapy was used to metabolically eliminate arsenic by forming a complex, but adverse effects limited their pharmacological use. More recently, plant-based products have been found to provide significant relief from the toxic effects of arsenic poisoning. They act by different mechanisms affecting various cellular processes. Phytoconstituents such as curcumin, quercetin, diallyl trisulfide, thymoquinone, and others act via various molecular pathways, primarily by attenuating oxidative damage, membrane damage, DNA damage, and proteinopathies. Nonetheless, most of the phytochemicals reviewed here protect against the adverse effects of metal or metalloid exposure, supporting their consideration as alternatives to chelation therapy. These agents, if used prophylactically and in conjunction with other chemotherapeutic agents, may provide an effective approach for management of arsenic toxicity. In a few instances, such strategies like coadministration of phytochemicals with a known chelating agent have led to more pronounced elimination of arsenic from the body with lesser off-site adverse effects. This is possible because combination treatment ensures the use of a reduced dose of chelating agent with a phytochemical without compromising treatment. Thus, these therapies are more practical than conventional therapeutic agents in ameliorating arsenic-mediated toxicity. This review summarizes the potential of phytochemicals in alleviating arsenic toxicity on the basis of available experimental and clinical evidence.
Subject(s)
Arsenic Poisoning , Arsenic , Animals , Arsenic/metabolism , Arsenic/toxicity , Arsenic Poisoning/drug therapy , Arsenic Poisoning/metabolism , Chelating Agents , Ecosystem , Phytochemicals/pharmacology , Phytochemicals/therapeutic use , Quality of LifeABSTRACT
Arsenic poisoning is a geochemical disease that seriously endangers human health. The liver is one of the important target organs for arsenic poisoning, several studies have shown that oxidative stress plays an important role in arsenic-induced liver damage. However, the specific mechanism of arsenic-induced oxidative stress has not yet been fully elucidated, and currently, there are no effective intervention measures for the prevention and treatment of arsenic-induced liver damage. In this study, the effect of the Nrf2/GPX4 signaling pathway and oxidative stress in the arsenic-induced liver damage was first evaluated. The results show that arsenic can activate the Nrf2/GPX4 signaling pathway and increase the oxidative stress, which in turn promotes arsenic-induced liver damage in MIHA cells. Moreover, when we applied the Nrf2 inhibitor, the promoting effect of arsenic on liver damage was alleviated by inhibiting the activation of the Nrf2/GPX4 signaling pathway. Subsequently, the Rosa roxburghii Tratt [Rosaceae] (RRT) intervention experiments in cells and arsenic poisoning population were designed. The results revealed that RRT can inhibit Nrf2/GPX4 signaling pathway to reduce oxidative stress, thereby alleviates arsenic-induced liver damage. This study provides some limited evidence that arsenite can activate Nrf2/GPX4 signaling pathway to induce oxidative stress, which in turn promotes arsenic-induced liver damage in MIHA cells. The second major finding was that Kaji-ichigoside F1 may be a potential bioactive compound of RRT, which can inhibit Nrf2/GPX4 signaling pathway to reduce oxidative stress, thereby alleviates arsenic-induced liver damage. Our study will contribute to a deeper understanding of the mechanisms in arsenic-induced liver damage, these findings will identify a possible natural medicinal food dual-purpose fruit, RRT, as a more effective prevention and control strategies for arsenic poisoning.
Subject(s)
Arsenic Poisoning , Arsenic , Plant Preparations , Rosa , Arsenic/toxicity , Arsenic Poisoning/metabolism , Arsenic Poisoning/prevention & control , Liver/metabolism , NF-E2-Related Factor 2/metabolism , Oxidative Stress , Rosa/chemistry , Animals , Plant Preparations/pharmacologyABSTRACT
The aim of this study was to investigate the effects of different doses of selenium (Se) on oxidative damage and neurotransmitter-related parameters in arsenic (As)-induced broiler brain tissue damage. Two hundred 1-day-old avian broilers were randomly divided into five groups and fed the following diets: control group (As 0.1 mg/kg + Se 0.2 mg/kg), As group (As 3 mg/kg + Se 0.2 mg/kg), low-Se group (As 3 mg/kg + Se 5 mg/kg), medium-Se group (As 3 mg/kg + Se 10 mg/kg), and high-Se group (As 3 mg/kg + Se 15 mg/kg). Glutathione (GSH), glutathione peroxidase (GSH-PX), nitric oxide (NO), nitric oxide synthase (NOS) activity, glutamate (Glu) concentration, glutamine synthetase (GS) activity, acetylcholinesterase (TchE) activity, and the apoptosis rate of brain cells were measured. The results showed that 3 mg/kg dietary As could induce oxidative damage and neurotransmitter disorder of brain tissue, increase the apoptosis rate of brain cells and cause damage to brain tissue, decrease activities of GSH and GSH-PX, decrease the contents of NO, decrease the activities of iNOS and tNOS, increase contents of Glu, and decrease activities of Gs and TchE. Compared with the As group, the Se addition of the low-Se and medium-Se groups protected against As-induced oxidative damage, neurotransmitter disorders, and the apoptosis rate of brain cells, with the addition of 10 mg/kg Se having the best effect. However, 15 mg/kg Se not only did not produce a protective effect against As damage but actually caused similar or severe damage.
Subject(s)
Arsenic Poisoning , Brain Injuries , Selenium , Acetylcholinesterase , Animals , Arsenic Poisoning/drug therapy , Chickens , Selenium/pharmacologyABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Due to the modernization of traditional Chinese medicine (TCM) and the influence of traditional medication habits (TCM has no toxicity or side effects), arsenic poisoning incidents caused by the abuse of realgar and realgar-containing Chinese patent medicines have occurred occasionally. However, the potential mechanism of central nervous system toxicity of realgar remains unclear. AIM OF THE STUDY: This study aimed to clarify the specific mechanism of realgar-induced neurotoxicity. MATERIALS AND METHODS: In this study, the roles of ERK1/2 and p38 MAPK in realgar-induced neuronal autophagy and overactivation of the nuclear factor erythroid-derived factor 2-related factor (Nrf2) signalling pathways was investigated in vivo and in vitro. RESULTS: The arsenic in realgar passed through the blood-brain barrier and accumulated in the brain, resulting in damage to neurons, synapses and myelin sheaths in the cerebral cortex and a decrease in the total antioxidant capacity. The specific mechanism is that the excessive activation of Nrf2 is regulated by the upstream signalling molecules ERK1/2 and p38MAPK. At the same time, p38 MAPK and ERK1/2 interfere with autophagy, thereby promoting autophagy initiation but causing subsequent dysfunctional autophagic degradation and inducing the p62-Keap1-Nrf2 feedback loop to promote Nrf2 signalling pathway activation and nerve cell apoptosis. CONCLUSIONS: This study confirmed the role of the signalling molecules p38 MAPK and ERK1/2 in perturbing autophagy and inducing the p62-Keap1-Nrf2 feedback loop to activate the Nrf2 signalling pathway in realgar-induced neurotoxicity.
Subject(s)
Apoptosis/drug effects , Arsenic Poisoning/metabolism , Arsenicals , Autophagy/drug effects , Kelch-Like ECH-Associated Protein 1/metabolism , MAP Kinase Signaling System/drug effects , NF-E2-Related Factor 2/metabolism , Oxidative Stress/drug effects , Sulfides , Animals , Arsenicals/pharmacokinetics , Cells, Cultured , Disease Models, Animal , Medicine, Chinese Traditional , Mice , Neurons/drug effects , Neurons/metabolism , Rats , Sulfides/pharmacokinetics , Sulfides/toxicity , Transcription Factor TFIIH/metabolismABSTRACT
OBJECTIVE: Chronic exposure to inorganic arsenic (iAs) may cause a number of health problems including skin cancer. Present study is aimed to look into the potential of black tea extract (BTE) to prevent the development of skin carcinoma in Swiss albino mice. METHODS: The study was done on Swiss albino mice, chronically exposed to inorganic arsenic. 150 mice were housed in different cages, 5 in each cage. The control mice did not receive any treatment. Mice were sacrificed at 30, 90, 180, 270 and 330 days. Development of carcinogenesis was assessed by histological studies. Generation of Reactive Oxygen Species (ROS) and Reactive Oxygen Species (RNS) were estimated using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) and Greiss reagent respectively, and their consequences on DNA (by Micronuclei and Comet assay), protein (by protein carbonyl assay kit) and lipid (by lipid peroxidation) were estimated. Activity of antioxidant enzymes, along with total antioxidant capacity were measured by respective kits. Repair percentage was obtained by Comet assay. Western blotting was employed to study the expression of repair enzymes and expression of cytokines. Sandwich Enzyme-linked Immunosorbent Assay (ELISA) technique was employed to study the activity of various cytokines. RESULTS: At 330 days, invasive squamous cell carcinoma of the skin developed. With increasing time generation of ROS and RNS increased, causing damage to DNA, protein and lipid. Antioxidant defence system gets repressed with time. Capacity to repair the DNA damage is inhibited by iAs, due to alteration in repair enzymes - XRCC I, DNA Ligase I, PARP I, ERCC1, ERCC2, XPA, DNA Ligase IV, DNA PKc and Ku-70. Another consequence of iAs exposure is chronic inflammation due to disrupted cytokine level. Intervention with BTE reverses these deleterious effects, preventing development of skin carcinogenesis.
Subject(s)
Arsenic Poisoning/drug therapy , Arsenicals , Carcinoma, Squamous Cell/prevention & control , Plant Extracts/pharmacology , Skin Neoplasms/prevention & control , Tea , Animals , Antioxidants/pharmacology , Arsenic Poisoning/complications , Carcinoma, Squamous Cell/chemically induced , DNA Damage/drug effects , Disease Models, Animal , Mice , Reactive Oxygen Species/metabolism , Skin Neoplasms/chemically inducedABSTRACT
This paper presents a new method for the simultaneous speciation analysis of arsenic (As(III)-arsenite, As(V)-arsenate, DMA-dimethylarsinic acid, MMA-methylarsonic acid, and AsB-arsenobetaine) and selenium (Se(IV)-selenite, Se(VI)-selenate, Se-Methionine, and Se-Cystine), which was applied to a variety of seafood and onion samples. The determination of the forms of arsenic and selenium was undertaken using the High-Performance Liquid Chromatography Inductively Coupled Plasma Mass Spectrometry (HPLC-ICP-MS) analytical technique. The separation of both organic and inorganic forms of arsenic and selenium was performed using two analytical columns: an anion exchange column, Dionex IonPac AS22, containing an alkanol quaternary ammonium ion, and a double bed cation-anion exchange guard column, Dionex Ion Pac CG5A, containing, as a first layer, fully sulfonated latex for cation exchange and a fully aminated layer for anion exchange as the second layer. The ammonium nitrate, at pH = 9.0, was used as a mobile phase. The method presented here allowed us to separate the As and Se species within 10 min with a suitable resolution. The applicability was presented with different sample matrix types: seafood and onion.
Subject(s)
Arsenic/analysis , Food Contamination/analysis , Onions/chemistry , Onions/toxicity , Seafood/analysis , Seafood/toxicity , Selenium/analysis , Animals , Arsenic Poisoning , Arsenicals/analysis , Chromatography, High Pressure Liquid , Chromatography, Ion Exchange , Humans , Mass Spectrometry , Organoselenium Compounds/analysis , Organoselenium Compounds/toxicity , Selenium Compounds/analysis , Selenium Compounds/toxicityABSTRACT
Arsenic (As) pollution is a serious and longstanding problem, which has obvious threaten to aquatic organisms. The study aimed to explore the mitigation effect of natural antioxidant zinc (Zn) on As toxicity in the foregut and midgut of common carp (Cyprinus carpio L.), and in-depth disclose related signal cascade. Carps were treated with Zn2+ (1 mg/L) and/or As3+ (2.83 mg/L) for a period of 30 days. Under As exposure, the foregut and midgut showed obvious burst of reactive oxygen species (ROS) and breakdown of antioxidant system. What followed is the activation of the endogenous and exogenous apoptotic pathways, and the rise of autophagy level prompted by the increase in LC3 II and the down-regulation of p62. Mitochondrial swelling, cristae fragmentation and autophagosomes were observed under the electron microscope, which also means the occurrence of apoptosis and autophagy. In addition, As induced the activation of p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK) and the inhibition of extracellular signal-related kinase (ERK) in MAPK signaling, and up-regulated the level of autophagy through the inhibition of the phosphatidylinositol 3 kinase (PI3K)/AKT/ mammalian target of rapamycin (mTOR) signaling cascade. However, Zn supplementation has clearly reversed the above phenomenon, and it basically has no effect on foregut and midgut. In conclusion, this study shows that Zn can alleviate the damage caused by subchronic As exposure, which provides a reference for the use of Zn preparations in aquaculture.
Subject(s)
Arsenic Poisoning , Carps , Water Pollutants, Chemical , Animals , Apoptosis , Extracellular Signal-Regulated MAP Kinases , Phosphatidylinositol 3-Kinase , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Reactive Oxygen Species , TOR Serine-Threonine Kinases , Water Pollutants, Chemical/toxicity , ZincABSTRACT
Arsenic is a well-recognized environmental contaminant that occurs naturally through geogenic processes in the aquifer. More than 200 million people around the world are potentially exposed to the elevated level of arsenic mostly from Asia and Latin America. Many adverse health effects including skin diseases (i.e., arsenicosis, hyperkeratosis, pigmentation changes), carcinogenesis, and neurological diseases have been reported due to arsenic exposure. In addition, arsenic has recently been shown to contribute to the onset of non-communicable diseases, such as diabetes mellitus and cardiovascular diseases. The mechanisms involved in arsenic-induced diabetes are pancreatic ß-cell dysfunction and death, impaired insulin secretion, insulin resistance and reduced cellular glucose transport. Whereas, the most proposed mechanisms of arsenic-induced hypertension are oxidative stress, disruption of nitric oxide signaling, altered vascular response to neurotransmitters and impaired vascular muscle calcium (Ca2+) signaling, damage of renal, and interference with the renin-angiotensin system (RAS). However, the contributions of arsenic exposure to non-communicable diseases are complex and multifaceted, and little information is available about the molecular mechanisms involved in arsenic-induced non-communicable diseases and also no suitable therapeutic target identified yet. Therefore, in the future, more basic research is necessary to identify the appropriate therapeutic target for the treatment and management of arsenic-induced non-communicable diseases. Several reports demonstrated that a daily balanced diet with proper nutrient supplements (vitamins, micronutrients, natural antioxidants) has shown effective to reduce the damages caused by arsenic exposure. Arsenic detoxication through natural compounds or nutraceuticals is considered a cost-effective treatment/management and researchers should focus on these alternative options. This review paper explores the scenarios of arsenic contamination in groundwater with an emphasis on public health concerns. It also demonstrated arsenic sources, biogeochemistry, toxicity mechanisms with therapeutic targets, arsenic exposure-related human diseases, and onsets of cardiovascular diseases as well as feasible management options for arsenic toxicity.