Toxic arsenolipids bioaccumulate in the developing brain of pilot whales.

Arsenic-containing hydrocarbons (AsHC), a subclass of arsenolipids (AsL), have been proven to exert neuro- and cytotoxic effects in in-vitro and in-vivo studies and were shown to pass through biological barriers like the blood-brain barrier. However, there has been no connection as to the environmental relevance of these findings, meaning there is no study based on samples from free living animals that are exposed to these compounds. Here, we report the identification of two AsHC as well as 3 arsenosugar phospholipids (AsPL) in the brains of a pod of stranded long-finned pilot whales (Globicephala melas) as well as the absence of arsenobetaine (AsB) which is often found to be a dominant As species in fish. We show data which suggests that there is an age-dependent accumulation of AsL in the brains of the animals. The results show that, in contrast to other organs, total arsenic as well as arsenolipids accumulate in an asymptotic pattern in the brains of the animals. Total As concentrations were found to range from 87 to 260 µg As/kg wet weight and between 0.6 and 27.6 µg As/kg was present in the form of AsPL958 in the brains of stranded pilot whales which was the most dominant lipophilic species present. The asymptotic relationship between total As, as well as AsPL, concentration in the brain and whale age may suggest that the accumulation of these species takes place prior to the full development of the blood-brain barrier in young whales. Finally, comparison between the organs of local squid, a common source of food for pilot whales, highlighted a comparable AsL profile which indicates a likely bioaccumulation pathway through the food chain.

Protein vicinal thiols as intrinsic probes of brain redox states in health, aging, and ischemia.

The nature of brain redox metabolism in health, aging, and disease remains to be fully established. Reversible oxidations, to disulfide bonds, of closely spaced (vicinal) protein thiols underlie the catalytic maintenance of redox homeostasis by redoxin enzymes, including thioredoxin peroxidases (peroxiredoxins), and have been implicated in redox buffering and regulation. We propose that non-peroxidase proteins containing vicinal thiols that are responsive to physiological redox perturbations may serve as intrinsic probes of brain redox metabolism. Using redox phenylarsine oxide (PAO)-affinity chromatography, we report that PAO-binding vicinal thiols on creatine kinase B and alpha-enolase from healthy rat brains were preferentially oxidized compared to other selected proteins, including neuron-specific (gamma) enolase, under conditions designed to trap in vivo protein thiol redox states. Moreover, measures of the extents of oxidations of vicinal thiols on total protein, and on creatine kinase B and alpha-enolase, showed that vicinal thiol-linked redox states were stable over the lifespan of rats and revealed a transient reductive shift in these redox couples following decapitation-induced global ischemia. Finally, formation of disulfide-linked complexes between peroxiredoxin-2 and brain proteins was demonstrated on redox blots, supporting a link between protein vicinal thiol redox states and the peroxidase activities of peroxiredoxins. The implications of these findings with respect to underappreciated aspects of brain redox metabolism in health, aging, and ischemia are discussed.

Speciation of arsenic in milk from cows fed seaweed.

BACKGROUND: Including seaweed in cattle feed has gained increased interest, but it is important to take into account that the concentration of toxic metals, especially arsenic, is high in seaweed. This study investigated the arsenic species in milk from seaweed-fed cows. RESULTS: Total arsenic in milk of control diets (9.3 ± 1.0 µg As kg-1, n = 4, dry mass) was significantly higher than seaweed-based diet (high-seaweed diet: 7.8 ± 0.4 µg As kg-1, P < 0.05, n = 4, dry mass; low-seaweed diet: 6.2 ± 1.0 µg As kg-1, P < 0.01, n = 4, dry mass). Arsenic speciation showed that the main species present were arsenobetaine (AB) and arsenate (As(V)) (37% and 24% of the total arsenic, respectively). Trace amounts of dimethylarsinic acid (DMA) and arsenocholine (AC) have also been detected in milk. Apart from arsenate being significantly lower (P < 0.001) in milk from seaweed-fed cows than in milk from the control group, other arsenic species showed no significant differences between groups. CONCLUSION: The lower total arsenic and arsenate in seaweed diet groups indicates a possible competition of uptake between arsenate and phosphate, and the presence of AC indicates that a reduction of AB occurred in the digestive tract. Feeding a seaweed blend (91% Ascophyllum nodosum and 9% Laminaria digitata) does not raise As-related safety concerns for milk. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

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.

Translocation, enzymatic reduction and toxicity of dimethylarsenate in rice.

Dimethylarsenate [DMAs(V)] can be produced by some soil microorganisms through methylation of inorganic arsenic (As), especially in anoxic paddy soils. DMAs(V) is more phytotoxic than inorganic As and can cause the physiological disorder straighthead disease in rice. Rice cultivars vary widely in the resistance to DMAs(V), but the mechanism remains elusive. Here, we investigated the differences in DMAs(V) uptake, translocation, and reduction to dimethylarsenite [DMAs(III)], as well as the effects on the metabolome, between two rice cultivars Mars and Zhe733. We found that Mars was 11-times more resistant to DMAs(V) than Zhe733. Mars accumulated more DMAs(V) in the roots, whereas Zhe733 translocated more DMAs(V) to the shoots and reduced more DMAs(V) to DMAs(III). DMAs(III) was more toxic than DMAs(V). Using heterologous expression and in vitro enzyme assays, we showed that the glutathione-S-transferases OsGSTU17 and OsGSTU50 were able to reduce DMAs(V) to DMAs(III). The expression levels of OsGSTU17 and OsGSTU50 were higher in the shoot of Zhe733 compared to Mars. Metabolomic analysis in rice shoots showed that glutathione (GSH) metabolism was perturbed by DMAs(V) toxicity in Zhe733. Application of exogenous GSH significantly alleviated the toxicity of DMAs(V) in Zhe733. Taken together, the results suggest that Mars is more resistant to DMAs(V) than Zhe733 because of a lower root-to-shoot translocation and a smaller capacity to reduce DMAs(V) to DMAs(III).

Study on arsenic speciation, bioaccessibility, and gut microbiota in realgar-containing medicines by DGT technique and artificial gastrointestinal extraction (PBET) combine with simulated human intestinal microbial ecosystem (SHIME).

It is well-known that several Chinese patent medicines use realgar as a specific component. People are more aware of the health dangers associated with realgar since it includes arsenic. Previous research overstated the arsenic toxicity of realgar-containing Chinese prescription medications because little thought was given to the influence of arsenic bioaccessibility by gut microbiota. In light of this, this study examined the total content, bioaccessibility and speciation of targeted medications while also examining intestinal epithelial transit utilizing the diffusive gradients in thin-films (DGT). All samples contained arsenic, and the bioaccessibilities of the colon, intestine and gastric regions ranged from 0.19% to 1.73%, 0.25-1.88% and 0.21-1.70% respectively. The range of DGT-bioaccessibility is 0.01-0.0018%. Three steps of analysis were conducted on inorganic As(III) and As(V). In health risk assessment, the ADDs and HQs of DGT-bioaccessibility were below the threshold levels when compared to computing average daily intake dose (ADD) and hazard quotient (HQ) by bioaccessibility of gastric, intestinal and colon. Additionally, Proteobacteria and Firmicutes were discovered to be the two predominant kinds of gut microbes in this study. Under arsenic exposure, the abundance of Christensenellaceae, Desulfovibrionaceae and Akkermansiaceae increased, but the quantity of Rikenellaceae decreased. These findings revealed that alterations in gut microbiota had an impact on host metabolism.

Arsenic exposure in northern Mexican women / Exposición a arsénico en mujeres del norte de México

Abstract: Objective: To describe interindividual metabolism variations and sociodemographic characteristics associated to urinary arsenic, and to estimate the arsenic contamination in water from urinary total arsenic (TAs). Materials and methods: Women (n=1 028) from northern Mexico were interviewed about their sociodemographic characteristics and their urinary concentrations of arsenic species were measured by liquid chromatography. Inorganic arsenic (iAs) in water was estimated from urinary TAs. Results: Women were 20-88 years old. TAs in urine ranged from p10=3.41 to p90=56.93 μg/L; 74% of women had levels >6.4 μg/L. iAs in water varied from p10=3.04 to p90=202.12 μg/L; 65% of women had concentrations >10 μg/L, and 41%, concentrations >25 μg/L. Large variations in iAs metabolism were observed. TAs was significantly negatively associated with age and schooling, and positively with the state of residence. Conclusion: Exposure to iAs is an environmental problem in Mexico. Individual variations in metabolism are a challenge to design prevention and control programs.

Resumen: Objetivo: Describir las variaciones interindividuales del metabolismo y las características sociodemográficas asociadas con el arsénico urinario, así como estimar su contaminación en el agua. Material y métodos. Se entrevistó a 1 028 mujeres del norte de México; por cromatografía de líquidos se midieron los metabolitos urinarios de arsénico y, a partir de ellos, se estimó la concentración en agua. Resultados: Las mujeres tuvieron 20-88 años. El arsénico urinario varió de p10=3.41 a p90=56.93 μg/L; 74% de las mujeres tuvieron niveles >6.4 μg/L. El arsénico en agua varió de p10=3.04 a p90=202.12 μg/L; 65% de las mujeres tenían concentraciones >10 μg/L, y 41%, >25 μg/L. Se observaron amplias variaciones en el metabolismo del arsénico. El arsénico urinario se asoció negativamente con la edad y escolaridad, y positivamente con el estado de residencia. Conclusión: La exposición a arsénico es un problema ambiental en México. Las variaciones individuales en su metabolismo son un desafío para diseñar programas de prevención y control.

Properties of realgar bioleaching using an extremely acidophilic bacterium and its antitumor mechanism as an anticancer agent

Realgar is a naturally occurring arsenic sulfide (or Xionghuang, in Chinese). It contains over 90% tetra-arsenic tetrasulfide (As4S4). Currently, realgar has been confirmed the antitumor activities, both in vitro and in vivo, of realgar extracted using Acidithiobacillus ferrooxidans (A. ferrooxidans). Bioleaching, a new technology to greatly improve the use rate of arsenic extraction from realgar using bacteria, is a novel methodology that addressed a limitation of the traditional method for realgar preparation. The present systematic review reports on the research progress in realgar bioleaching and its antitumor mechanism as an anticancer agent. A total of 93 research articles that report on the biological activity of extracts from realgar using bacteria and its preparation were presented in this review. The realgar bioleaching solution (RBS) works by inducing apoptosis when it is used to treat tumor cells in vitro and in vivo. When it is used to treat animal model organisms in vivo, such as mice and Caenorhabditis elegans, tumor tissues grew more slowly, with mass necrosis. Meanwhile, the agent also showed obvious inhibition of tumor cell growth. Bioleaching technology greatly improves the utilization of realgar and is a novel methodology to improve the traditional method.

Genetic polymorphisms of PPAR gamma, arsenic methylation capacity and breast cancer risk in Mexican women / Polimorfismos genéticos de PPAR gamma, capacidad de metilación del arsénico y riesgo de cáncer de mama en mujeres mexicanas

Abstract Objective: To evaluate whether the presence of polymorphisms of peroxisome proliferator-activated receptor gamma PPARγ (Pro 1 2Ala) and PPARGC1B (Ala203Pro) modifies the association between the inorganic arsenic (iAs) methylation capacity and breast cancer (BC). Materials and methods: Mexican women were interviewed, and blood and urine samples were collected from them (cases/controls= 197/220). The concentration of urinary arsenic species and the polymorphisms of interest were determined by high-performance liquid chromatography with inductively coupled plasma mass spectrometry (HPLC-ICP-MS) and polymerase chain reaction (PCR), respectively. Results: In women with a high %MMA (urinary monomethyl arsenic) and high primary methylation ratio (PM = MMA/iAs), the risk of BC was increased (odds ratio [OR]%MMA T3 vs.T1= 3.60: 95% confidence interval [CI] 2.02-6.41, ORPMI T3 vs.T1= 3.47: 95%CI 1.95-6.17), which was maintained after adjusting for polymorphisms. No significant interactions were observed between the polymorphisms and the arsenic variables on the risk of BC. Conclusion: Pro 12Ala and Ala203Pro polymorphisms did not modify the association between the iAs methylation capacity and BC.

Resumen Objetivo: Evaluar si la presencia de polimorfismos de PPARγ (Pro 1 2Ala) y PPARGC1B (Ala203Pro) modifica la asociación entre la capacidad de metilación del arsénico inorgánico (Asi) y el cáncer de mama (CM). Material y métodos: Se entrevistaron mujeres mexicanas y recolectaron muestras de sangre y orina de (casos/controles=197/220). La concentración de especies de arsénico urinario y los polimorfismos de interés se determinaron mediante cromatografía líquida de alta resolución acoplada a espectrometría de masas (HPLC-ICP-MS) y reacción en cadena de la polimerasa (PCR), respectivamente. Resultados: En mujeres con %MMA (monometilarsénico urinario) y razón de primera metilación altas (PM=MMA/Asi) se incrementó el riesgo de CM (RM%MMAT3vsT1=3.60: intervalo de confianza [IC]95%2.02-6.41, RMPMT3vs.T1=3.47:IC95%1.95-6.17), que se mantuvo, respectivamente, al ajustar por polimorfismos. No se observaron interacciones significativas entre los polimorfismos y las variables arsenicales sobre el riesgo de CM. Conclusión: Los polimorfismos Pro 12Ala y Ala203Pro no modificaron la asociación entre la capacidad de metilación del Asi y el CM.