Gut microbiota deficiency aggravates arsenic-induced toxicity by affecting bioaccumulation and biotransformation in C57BL/6J mice.

Gut microbiome can influence the arsenic metabolism in mammals. Confusingly, gut microbiome was found to both mitigate and exacerbate arsenic toxicity. In this study, the role of gut microbiota in arsenic bioaccumulation, biotransformation, and organ toxicity in C57BL/6J mice was investigated. Gut microbiota deficiency model was established by antibiotics (Ab) cocktail AVNM. Conventional and gut microbiota deficiency mice were exposed to NaAsO2 for 4 weeks. Comparing with Ab-treated mice, the total arsenic (tAs) in the tissues was significantly reduced in conventional mice, which was opposed to the results of those in feces. Interestingly, dimethyl arsenite (DMA) was the most abundant metabolite in the feces of Ab-treated mice, while arsenic acid (AsV) had the highest proportion in the feces of conventional mice with approximately 16-fold than that in Ab-treated mice, indicating the critical role of gut microbiota in metabolizing arsenious acid (AsIII) to AsV. Additionally, the liver and kidney in Ab-treated mice showed more severe pathological changes and apoptosis. The significant increased level of ionized calcium-binding adapter molecule 1 (IBA-1) was also found in the brains of Ab-treated mice. Our results indicated that gut microbiota protected the host from arsenic-induced toxicity in liver, kidney, and brain by reducing the arsenic accumulation.

Gestational α-ketoglutarate supplementation ameliorates arsenic-induced hepatic lipid deposition via epigenetic reprogramming of ß-oxidation process in female offspring.

Inorganic trivalent arsenic (iAsⅢ) at environmentally relevant levels has been found to cause developmental toxicity. Maternal exposure to iAsⅢ leads to enduring hepatic lipid deposition in later adult life. However, the exact mechanism in iAsⅢ induced hepatic developmental hazards is still unclear. In this study, we initially found that gestational exposure to iAsⅢ 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 iAsⅢ. 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 iAsⅢ 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.

Environmental arsenic pollution induced liver oxidative stress injury by regulating miR-155 through inhibition of AUF1.

Arsenic (As), a common environmental pollutant, has become a hot topic in recent years due to its potentially harmful effects. Liver damage being a central clinical feature of chronic arsenic poisoning. However, the underlying mechanisms remain unclear. We demonstrated that arsenic can lead to oxidative stress in the liver and result in structural and functional liver damage, significantly correlated with the expression of AUF1, Dicer1, and miR-155 in the liver. Interestingly, knockdown AUF1 promoted the up-regulatory effects of arsenic on Dicer1 and miR-155 and the inhibitory effects on SOD1, which exacerbated oxidative damage in rat liver. However, overexpression of AUF1 reversed the up-regulatory effects of arsenic on Dicer1 and miR-155, restored arsenic-induced SOD1 depletion, and attenuated liver oxidative stress injury. Further, we verified the mechanism and targets of miR-155 in regulating SOD1 by knockdown/overexpression of miR-155 and nonsense mutant SOD1 3'UTR experiments. In conclusion, these results powerfully demonstrate that arsenic inhibits AUF1 protein expression, which in turn reduces the inhibitory effect on Dicer1 expression, which promotes miR-155 to act on the SOD1 3'UTR region after high expression, thus inhibiting SOD1 protein expression and enzyme activity, and inducing liver injury. This finding provides a new perspective for the mechanism research and targeted prevention of arsenic poisoning, as well as scientific evidence for formulating strategies to prevent and control environmental arsenic pollution.

Neurotoxic effects of heavy metal pollutants in the environment: Focusing on epigenetic mechanisms.

The pollution of heavy metals (HMs) in the environment is a significant global environmental issue, characterized by its extensive distribution, severe contamination, and profound ecological impacts. Excessive exposure to heavy metal pollutants can damage the nervous system. However, the mechanisms underlying the neurotoxicity of most heavy metals are not completely understood. Epigenetics is defined as a heritable change in gene function that can influence gene and subsequent protein expression levels without altering the DNA sequence. Growing evidence indicates that heavy metals can induce neurotoxic effects by triggering epigenetic changes and disrupting the epigenome. Compared with genetic changes, epigenetic alterations are more easily reversible. Epigenetic reprogramming techniques, drugs, and certain nutrients targeting specific epigenetic mechanisms involved in gene expression regulation are emerging as potential preventive or therapeutic tools for diseases. Therefore, this review provides a comprehensive overview of epigenetic modifications encompassing DNA/RNA methylation, histone modifications, and non-coding RNAs in the nervous system, elucidating their association with various heavy metal exposures. These primarily include manganese (Mn), mercury (Hg), lead (Pb), cobalt (Co), cadmium (Cd), nickel (Ni), sliver (Ag), toxic metalloids arsenic (As), and etc. The potential epigenetic mechanisms in the etiology, precision prevention, and target therapy of various neurodevelopmental disorders or different neurodegenerative diseases are emphasized. In addition, the current gaps in research and future areas of study are discussed. From a perspective on epigenetics, this review offers novel insights for prevention and treatment of neurotoxicity induced by heavy metal pollutants.

Study on the mechanism of arsenic-induced renal injury based on SWATH proteomics technology.

BACKGROUND: Arsenic (As) poisoning is a worldwide endemic disease affecting thousands of people. As is excreted mainly through the renal system, and arsenic has toxic effects on the kidneys, but the mechanism has not been elucidated. In this study, the molecular basis of arsenic's nephrotoxicity was studied by using a high-throughput proteomics technique. METHODS: Eight SD (Sprague-Dawley) rats, half male and half female, were fed an As diet containing 50 mg/kg NaAsO2. Age- and sex-matched rats fed with regular chow were used as controls. At the end of the experiment (90 days), kidney tissue samples were collected and assessed for pathological changes using hematoxylin-eosin staining. Proteomic methods were used to identify alterations in protein expression levels in kidney tissues, and bioinformatic analyses of differentially expressed proteins between arsenic-treated and control groups were performed. The expression of some representative proteins was validated by Western blot analysis. RESULTS: NaAsO2 could induce renal injury. Compared with the control group, 112 proteins were up-regulated, and 46 proteins were down-regulated in the arsenic-treated group. These proteins were associated with the electron transport chain, oxidative phosphorylation, mitochondrial membrane, apoptosis, and proximal tubules, suggesting that the mechanisms associated with them were related to arsenic-induced kidney injury and nephrotoxicity. The expressions of Atp6v1f, Cycs and Ndufs1 were verified, consistent with the results of omics. CONCLUSION: These results provide important evidence for arsenic-induced kidney injury and provide new insights into the molecular mechanism of arsenic-induced kidney injury.

Mitigation of arsenic poisoning induced oxidative stress and genotoxicity by Ocimum gratissimum L.

Arsenic toxicity is a major problem across the world due to geogenic activity and has been supposed to generate free radicals and genotoxicity among the arsenic-poisoned population. There is a need to find suitable free radical quenching compounds for the arsenic-induced free radical-affected population. In the present study, Na3AsO3- induced oxidative stress and genotoxicity were evaluated in Oryctolagus cuniculus L, and quenching competency of Ocimum species was examined by applying enzymatic and non-enzymatic in vitro tests, comet assay, and Random Amplified Polymorphic Deoxyribonucleic acid - Polymerase Chain Reaction (RAPD-PCR) methods. In the present study, oxidative damage due to Na3AsO3 intoxication in O. cuniculus L has been confirmed followed by substantive genotoxicity, and in a further study, it has also been reported that the extract of O. gratissimum L lowers the oxidative stress in experimental animals confirmed by a decrease in Malondialdehyde (MDA) 4.78 ± 0.05 (nmol/mg protein), and an increase in Glutathione (GSH) 2.87 ± 0.50 (µmoles/mg proteins), Superoxide Dismutase (SOD) 1.78 ± 0.03(Units/mg protein), Catalase (CAT) 2.72 ± 0.02 (µmoles of H2O2 consumed/min/mg proteins) and Glutathione peroxidase (GPX) 7.43 ± 0.01 (µg of glutathione utilized/min/mg protein). A positive impact of extract of O. gratissimum L on protection of genotoxicity has been also confirmed by Random Amplified Polymorphic DNA (RAPD) based reduction in polymorphic bands of Deoxyribonucleic acid (DNA) from 6.5 to 3.16 and comet assay-based increase in head DNA % (87.86 ± 1.58), tail moment (1.07 ± 0.27) and decrease in tail DNA % (12.13 ± 1.58) & tail length (8.2 ± 1.46) at 5% P in lymphocytes. A significant level reduction in free radicals and reduction in DNA polymorphism has proved the competency of test material for the development of suitable antidotes against arsenicosis.

Microbial consortia-mediated arsenic bioremediation in agricultural soils: Current status, challenges, and solutions.

Arsenic poisoning in agricultural soil is caused by both natural and man-made processes, and it poses a major risk to crop production and human health. Soil quality, agricultural production, runoff, ingestion, leaching, and absorption by plants are all influenced by these processes. Microbial consortia have become a feasible bioremediation technique in response to the urgent need for appropriate remediation solutions. These diverse microbial populations collaborate to combat arsenic poisoning in soil by facilitating mechanisms including oxidation-reduction, methylation-demethylation, volatilization, immobilization, and arsenic mobilization. The current state, problems, and remedies for employing microbial consortia in arsenic bioremediation in agricultural soils are examined in this review. Among the elements affecting their success include diversity, activity, community organization, and environmental conditions. Also, we emphasize the sensitivity and accuracy limits of existing assessment techniques. While earlier reviews have addressed a variety of arsenic remediation options, this study stands out by concentrating on microbial consortia as a viable strategy for arsenic removal and presents performance evaluation and technical problems. This work gives vital insights for tackling the major issue of arsenic pollution in agricultural soils by explaining the potential methods and components involved in microbial consortium-mediated arsenic bioremediation.

Targeting the 'DNA methylation mark': Analysis of early epigenetic-alterations in children chronically exposed to arsenic.

Chronic exposure to arsenic causes adverse health effects in children. Aberrant epigenetic modifications including altered DNA methylation pattern are one of the major steps towards malignant transformation of cells. Our group has previously identified significant alteration in DNA methylation mark in arsenic exposed adults, affecting major biological pathways. Till date, no information is available exploring the altered DNA methylation mark in telomere regulation and altered mitochondrial functionality in association with DNA damage in arsenic-exposed children. Our study aims in identifying signature epigenetic pattern associated with telomere lengthening, mitochondrial functionality and DNA damage repair in children with special emphasis on DNA methylation. Biological samples (blood and urine) and drinking water were collected from the children aged between 5 and 16 years of arsenic exposed areas (N = 52) of Murshidabad district and unexposed areas (N = 50) of East Midnapur districts, West Bengal, India. Methylation-specific PCR was performed to analyse subtelomeric methylation status and promoter methylation status of target genes. Results revealed altered DNA methylation profile in the exposed children compared to unexposed. Promoter hypermethylation was observed in MLH1 and MSH2 (p < 0.05 and p < 0.001) indicating inefficiency in DNA damage repair. Hypomethylation in mitochondrial D-loop (p < 0.05) and TFAM promoter region (p < 0.05) along with increased mitochondrial DNA copy number among exposed children was also observed. Significant increase in telomere length and region specific subtelomeric hypermethylation (XpYp, p < 0.05) was found. Analysis of S-Adenosyl Methionine (SAM) and 8-oxoDG level revealed significant depletion of SAM (p < 0.001) and elevated oxidative DNA damage (p < 0.001) respectively in arsenic toxicity. Our study identified key methylation patterns in arsenic-exposed children which may act as an early predictive biomarker in the near future. Further in-depth studies involving large sample size and transcriptomic analysis are required for understanding the mechanistic details.

Accumulation characteristics of metals in human breast milk and association with dietary intake in northeastern China.

The trace elements present in breast milk play a vital role in the growth and development of infants. Nevertheless, numerous studies have reported the presence of toxic metal contamination in breast milk from various countries and regions, which poses potential risks to breastfed infants. This article aimed to investigate the characteristics of trace elements in breast milk and explore the relationship between breast milk and diet in Dalian, a coastal city in northeastern China. Breast milk samples and representative local food samples were collected from Dalian for research. The results revealed that 57 % of breast milk samples significantly exceeded the WHO safety limit (0.6 µg/L) for arsenic, with a measured mean value of 0.96 µg/L. Moreover, the levels of chromium (mean value: 2.63 µg/L) in 34 % of breast milk samples exceed the WHO recommended safety level (chromium: 1.5 µg/L). Aquatic foods accounted for 60 % to 90 % of the total intake of arsenic, cadmium, vanadium, mercury, and lead. The Spearman correlation analysis demonstrated strong positive correlations among breast milk metal elements, including copper-zinc (r = 0.68) and nickel­chromium (r = 0.89). Furthermore, the food-to-milk accumulation factors (FMAF) of strontium, nickel, arsenic, vanadium, cadmium, and mercury were relatively low (median values <0.005). While the FMAF values for chromium and lead were higher, with median values of 0.038 and 0.07, respectively. The results indicated potential risks of the toxic metal arsenic in breast milk from Dalian, China for breastfed infants. Therefore, continuous monitoring of breast milk for toxic metals and foodborne contamination is necessary.

Identification of novel NRF2-dependent genes as regulators of lead and arsenic toxicity in neural progenitor cells.

Lead (Pb) and arsenic (As) are prevalent metal contaminants in the environment. Exposures to these metals are associated with impaired neuronal functions and adverse effects on neurodevelopment in children. However, the molecular mechanisms by which Pb and As impair neuronal functions remain poorly understood. Here, we identified F2RL2, TRIM16L, and PANX2 as novel targets of Nuclear factor erythroid 2-related factor 2 (NRF2)-the master transcriptional factor for the oxidative stress response-that are commonly upregulated with both Pb and As in human neural progenitor cells (NPCs). Using a ChIP (Chromatin immunoprecipitation)-qPCR assay, we showed that NRF2 directly binds to the promoter region of F2RL2, TRIM16L, and PANX2 to regulate expression of these genes. We demonstrated that F2RL2, PANX2, and TRIM16L have differential effects on cell death, proliferation, and differentiation of NPCs in both the presence and absence of metal exposures, highlighting their roles in regulating NPC function. Furthermore, the analyses of the transcriptomic data on NPCs derived from autism spectrum disorder (ASD) patients revealed that dysregulation of F2RL2, TRIM16L, and PANX2 was associated with ASD genetic backgrounds and ASD risk genes. Our findings revealed that Pb and As induce a shared NRF2-dependent transcriptional response in NPCs and identified novel genes regulating NPC function. While further in vivo studies are warranted, this study provides a novel mechanism linking metal exposures to NPC function and identifies potential genes of interest in the context of neurodevelopment.

Co-exposure of nanoplastics and arsenic causes neurotoxicity in zebrafish (Danio rerio) through disrupting homeostasis of microbiota-intestine-brain axis.

Nanoplastics (NPs) and arsenic (As) are toxic pollutants prevalent on the earth and have gained considerable attention in recent decades. Although numerous studies reported NPs and As can cause neurotoxicity there are still significant knowledge gaps in illustrating their combined toxicity and its mechanism. In this study, the co-exposure of environmentally relevant concentrations of NPs and As caused neurobehavioral toxicity in zebrafish, as evidenced by reduced swimming ability, anxiety and impaired short-term learning memory. Potentially, its toxicity mechanism is through disrupting the homeostasis of microbiota-intestine-brain axis in zebrafish. Specifically, the co-exposure reduced the 5-hydroxytryptamine (5-HT) production in intestine, which led to lower levels of 5-HT transported by the blood circulation to the brain. Ultimately, neurobehavior was adversely affected by the reduced binding of 5-HT to its receptors. Intestine, the primary source of 5-HT, its impaired health (aggravation in oxidative stress, mitochondrial damage and histopathological alterations) induced the dysregulation in the 5-HT system, which may be induced by the increased accumulation of As in the intestine by the co-exposure. Besides, the reduced 5-HT levels were correlated with decreased Firmicutes and Protecbacteria and increased Actinobacteriota and Chloroflexi in intestines. Potentially, intestinal microbiota adversely regulates the intestine-brain axis by reducing SCFAs levels. Thus, the alteration of intestinal microbiota structure may be the other reason for the dysregulation of intestine-brain axis. In summary, co-exposure of NPs and As induced neurobehavior toxicity probably through disrupting the homeostasis of microbiota-intestine-brain axis. This study provides insights into assessing the environmental health risks of the pollution of NPs and As to aquatic organisms.

Methylation and bio-accessibility assessment of arsenate in crickets (Gryllusbimaculatus).

The ability of an organism to biomethylate toxic inorganic arsenic (As) determines both, the amount of As available for uptake higher up the food chain and the toxicity of bioavailable As. An exposure study was conducted to determine ability of farmed crickets to metabolize dietary arsenate. Crickets were exposed to 1.3 ± 0.1, 5.1 ± 2.5 and 36.3 ± 5.6 mg kg-1 dietary arsenate and quantitation of total As showed retention of 0.416 ± 0.003, 1.3 ± 0.04 and 2.46 ± 0.09 mg kg-1, respectively. Speciation analysis revealed that crickets have well developed ability to biomethylate dietary arsenate and the most abundant methylated As compound was DMA followed by MMA, TMAO and an unknown compound. Arsenobetaine, although present in all feed, control and As-rich, was measured only in the control crickets. To assess the bio-accessibility of the As species, crickets were subjected to simulated gastrointestinal digestion. The results showed that majority of As was extracted in saliva, followed by gastric and intestinal juice, which mass fraction was equal to residue. Over 78% of total As was shown to be bio-accessible with methylated species reaching 100% and iAs over 79% bio-accessibility. Additionally, arsenite and arsenate have shown different distributions between sequential leachate solutions. Bioaccumulation of As was observed in the studied crickets although it does not seem to occur to the same extent at higher exposure levels.

Returning personal genetic information on susceptibility to arsenic toxicity to research participants in Bangladesh.

BACKGROUND: There is growing consensus that researchers should offer to return genetic results to participants, but returning results in lower-resource countries has received little attention. In this study, we return results on genetic susceptibility to arsenic toxicity to participants in a Bangladeshi cohort exposed to arsenic through naturally-contaminated drinking water. We examine the impact on behavioral changes related to exposure reduction. METHODS: We enrolled participants from the Health Effects of Arsenic Longitudinal Study who had (1) high arsenic (≥150 µg/g creatinine) in a recent urine sample and (2) existing data on genetic variants impacting arsenic metabolism efficiency (AS3MT and FTCD). We used genetic data to recruit three study groups, each with n = 103: (1) efficient metabolizers (low-risk), (2) inefficient metabolizers (high-risk), and (3) a randomly-selected control group (NCT05072132). At baseline, all participants received information on the effects of arsenic and how to reduce exposure by switching to a low arsenic well. The two intervention groups also received their arsenic metabolism efficiency status (based on their genetic results). Changes in behavior and arsenic exposure were assessed using questionnaires and urine arsenic measures after six months. RESULTS: Clear decreases in urine arsenic after six months were observed for all three groups. The inefficient group self-reported higher levels of attempted switching to lower arsenic wells than the other groups; however, there was no detectable difference in urine arsenic reduction among the three groups. Participants showed strong interest in receiving genetic results and found them useful. The inefficient group experienced higher levels of anxiety than the other groups. Among the efficient group, that receiving genetic results did not appear to hinder behavioral change. CONCLUSION: Returning genetic results increased self-reported exposure-reducing behaviors but did not have a detectable impact on reducing urine arsenic over and above a one-on-one educational intervention.

[Arsenic Poisoning, in Murder is Easy].

Agatha Christie's detective novel Murder is Easy has the title with the message that the perpetrator of a serial murder in the English countryside was actually an unimaginable individual, and that murder is easy unless it is imagined. In the novel, arsenic is used as a murder tool. Therefore, and this essay aims to educate the readers about the neurological symptoms of arsenic poisoning. In the future, criminal acts using arsenic may appear before us. For reliable diagnosis, it is a major premise to have the basic knowledge written here; simultaneously, this novel shows that flexible thinking that is not bound by common sense is also required.

Mechanisms Associated with Cognitive and Behavioral Impairment Induced by Arsenic Exposure.

Arsenic (As) is a metalloid naturally present in the environment, in food, water, soil, and air; however, its chronic exposure, even with low doses, represents a public health concern. For a long time, As was used as a pigment, pesticide, wood preservative, and for medical applications; its industrial use has recently decreased or has been discontinued due to its toxicity. Due to its versatile applications and distribution, there is a wide spectrum of human As exposure sources, mainly contaminated drinking water. The fact that As is present in drinking water implies chronic human exposure to this metalloid; it has become a worldwide health problem, since over 200 million people live where As levels exceed safe ranges. Many health problems have been associated with As chronic exposure including cancer, cardiovascular diseases, gastrointestinal disturbances, and brain dysfunctions. Because As can cross the blood-brain barrier (BBB), the brain represents a target organ where this metalloid can exert its long-term toxic effects. Many mechanisms of As neurotoxicity have been described: oxidative stress, inflammation, DNA damage, and mitochondrial dysfunction; all of them can converge, thus leading to impaired cellular functions, cell death, and in consequence, long-term detrimental effects. Here, we provide a current overview of As toxicity and integrated the global mechanisms involved in cognitive and behavioral impairment induced by As exposure show experimental strategies against its neurotoxicity.

Protective effects of macromolecular polyphenols, metals (zinc, selenium, and copper) - Polyphenol complexes, and different organs with an emphasis on arsenic poisoning: A review.

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.

The protective effect of apigenin against inorganic arsenic salt-induced toxicity in PC12 cells.

Poisoning by arsenic affects people worldwide, and many human illnesses and health issues, including neurotoxicity, have been linked to chronic exposure to arsenic. When exposed to arsenic, the body produces intracellular reactive oxygen species (ROS), which influence a variety of alterations in cellular activity and directly harm molecules through oxidation. Arsenic-induced lesions are improved by antioxidants with the ability to lower ROS levels. Therefore, the current research aimed to assess how well apigenin protected PC12 cells from the toxicity caused by inorganic arsenic salt (iAs). For 24 and 48 h, iAs and/or apigenin were applied to PC12 cells. Then, oxidative stress indicators like malondialdehyde (MDA), nitric oxide (NO), and ROS in addition to the enzymatic and non-enzymatic antioxidant molecules such as catalase (CAT), glutathione (GSH), and superoxide dismutase (SOD) were assessed. Moreover, after exposure to iAs, PC12 was examined for nuclear factor erythroid 2-related factor 2 (Nrf2) expression to clarify how apigenin manifests its neuroprotection. Furthermore, NF-kB p65 concentration and IL-1B, IL-6, and TNF-α mRNA expression were measured to assess neuroinflammation. Bax, caspase-3, and Bcl-2 levels were measured to investigate apigenin's potential to protect PC12 cells from iAs poisoning. The obtained results revealed that, the cell survival rate in the iAs group was significantly lower (P < 0.05), and the number of viable cells steadily increased after apigenin treatment. Furthermore, the study found that iAs decreased GSH, CAT, and SOD in the PC12 cells while increasing ROS, MDA, and NO levels. In PC12 cells, the capacity of iAs to cause oxidative stress was linked to the induction of neuroinflammation and apoptosis. Interestingly, apigenin pre-treatment of PC12 cells resulted in exceptional protection against iAs-induced neuroinflammation, oxidative stress, and apoptotic cell death. Nrf2 upregulation in PC12 cells may explain the neuroprotection effect of apigenin against iAs toxicity. In conclusion, the obtained results of the present study have clinical significance and indicate that apigenin is a promising candidate for shielding the nervous system from toxic effects caused by arsenic. These findings require further investigation using in vivo experimental models.

Assessing the health risks of coal-burning arsenic-induced skin damage: A 22-year follow-up study in Guizhou, China.

Risk assessment of arsenic-induced skin damage has always received significant global attention. Theories derived from arsenic exposure in drinking water may not be applicable to the coal-burning type to arsenic-exposed area. Furthermore, very few studies have successfully determined the reference value of cumulative arsenic (CA) exposure that leads to specific skin lesions. In this study, we conducted a 22-year follow-up investigation to assess the risk of skin lesions and cancer resulting from long-term, multi-channel arsenic exposure from hazard identification, dose-response assessment, exposure assessment, and risk characterization. The results show that the arsenic exposure can significantly increase the prevalence of skin lesions. For each interquartile range increase of hair arsenic (HA) and CA, the risk of skin damage increased by 1.91 and 3.90 times, respectively. The lower confidence limit of the benchmark dose of HA of arsenic-induced various skin lesions ranged from 0.07 to 0.12 µg·g-1, and 932.57 to 1368.92 mg for CA. The chronic daily intake, lifetime average daily dose in the arsenic-exposed area after the comprehensive prevention and control measures have decreased significantly, but remained higher than the daily baseline level of 3.0 µg·kg-1·d-1. Even as recently as 2020, the hazard quotients and hazard index still exceeded 1, measuring 155.33 and 55.20, and the lifetime excess risk of skin cancer (2.80 × 10-3) remains significantly higher than the acceptable level of 10-6. Our study underscores the effectiveness of comprehensive prevention and control measures in managing high arsenic exposure in coal-burning arsenic poisoning areas. However, it is crucial to acknowledge that the risk of both non-carcinogenic and carcinogenic effects on the skin remains substantially higher than the acceptable level. We recommend setting reference limits for monitoring skin damage among individuals exposed to arsenic, with a recommended upper limit of 0.07 µg·g-1 for HA and a maximum acceptable level of 935.57 mg for CA.

Current advances in the detection and removal of organic arsenic by metal-organic frameworks.

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.

Arsenic toxicity to earthworms in soils of historical As mining sites: an assessment based on various endpoints and chemical extractions.

Eisenia fetida is an earthworm species often used to assess the toxicity of contaminants in soils. Several studies indicated that its response can be unpredictable because it depends both on total concentrations of contaminants and also on their forms that differ in susceptibility to be released from soil solid phase. The issue is complex because two various uptake routes are concurrently involved, dermal and ingestion in guts, where the bioavailability of contaminants can considerably change. The aim of this study was to analyze the toxicity of arsenic (As) in various strongly contaminated meadow and forest soils, representative for former As mining and processing area, to earthworms E. fetida and its accumulation in their bodies. An attempt was made to find relationships between the response of earthworms and chemical extractability of As. In the bioassay, carried out according to the standard ISO protocol, different endpoints were applied: earthworm survival, fecundity measured by the numbers of juveniles and cocoons, earthworm weight and As accumulation in the bodies. The results proved that E. fetida can tolerate extremely high total As concentrations in soils, such as 8000 mg/kg, however, the individual endpoints were not correlated and showed different patterns. The most sensitive one was the number of juveniles. No particular soil factor was identified that would indicate an exceptionally high As susceptibility to the release from one of soils, however, we have demonstrated that the sum of non-specifically and specifically bound As (i.e. fractions F1 + F2 in sequential extraction according to Wenzel) could be a good chemical indicator of arsenic toxicity to soil invertebrates.