Mechanisms of genotoxicity and proteotoxicity induced by the metalloids arsenic and antimony.

Arsenic and antimony are metalloids with profound effects on biological systems and human health. Both elements are toxic to cells and organisms, and exposure is associated with several pathological conditions including cancer and neurodegenerative disorders. At the same time, arsenic- and antimony-containing compounds are used in the treatment of multiple diseases. Although these metalloids can both cause and cure disease, their modes of molecular action are incompletely understood. The past decades have seen major advances in our understanding of arsenic and antimony toxicity, emphasizing genotoxicity and proteotoxicity as key contributors to pathogenesis. In this review, we highlight mechanisms by which arsenic and antimony cause toxicity, focusing on their genotoxic and proteotoxic effects. The mechanisms used by cells to maintain proteostasis during metalloid exposure are also described. Furthermore, we address how metalloid-induced proteotoxicity may promote neurodegenerative disease and how genotoxicity and proteotoxicity may be interrelated and together contribute to proteinopathies. A deeper understanding of cellular toxicity and response mechanisms and their links to pathogenesis may promote the development of strategies for both disease prevention and treatment.

Antimony toxicity upon microorganisms from aerobic and anaerobic environments.

Antimony (Sb) is a toxic and carcinogenic metalloid that can be present in contaminated water generated by mining operations and other industrial activities. The toxicity of Sb (III) and Sb (V) to aerobic microorganisms remains limited and unexplored for anaerobic microorganisms involved in hydrogen (H2) and methane (CH4) production. This study aimed to evaluate the toxicity of Sb (III) and Sb (V) upon aerobic and anaerobic microorganisms important in biological wastewater treatment systems. Sb (III) was more toxic than Sb (V) independently of the test and environment evaluated. Under aerobic conditions maintained in the Microtox assay, Sb (V) was not toxic to Allivibrio fischeri at concentrations as high as 500 mg/L, whereas Sb (III) caused just over 50% inhibition at concentration of 250 mg/L after 5 min of exposure. In the respirometry test, for the specific oxygen uptake rate, the concentrations of Sb (III) and Sb (V) displaying 50% inhibition were 0.09 and 56.2 mg/L, respectively. Under anaerobic conditions, exposure to Sb (III) and Sb (V) led to a decrease in microorganisms activity of fermentative and methanogenic processes. The results confirm that the microbial toxicity of Sb depends on its speciation and Sb (III) displays a significantly higher inhibitory potential than Sb (V) in both aerobic and anaerobic environments.

Influence of soil properties and aging on exogenous antimony toxicity to Caenorhabditis elegans in agricultural soil.

Exploring the influence of soil on antimony (Sb) aging could help predict Sb toxicity on nematodes that play an important role in agricultural soil nitrogen cycling. This study aimed to investigate the major soil factors affecting the aging process and toxicity of exogenous Sb. Therefore, nematodes were exposed to varying levels of Sb contamination (0-6400 mg/kg) in nine agricultural soils, with aging periods of 7, 56, and 168 days, under dark conditions at 20 ± 0.5 °C for 96 h. The results suggested that nematode reproduction was more sensitive to the toxicity of exogenous trivalent Sb (Sb(III)) compared to growth and fertility. Following 7-168 days of aging, the EC50 of nematode reproduction increased from 546-1557 to 3560-6193 mg/kg in nine soils contaminated by exogenous Sb(III). Exogenous Sb(III) toxicity is overestimated without considering its aging process. The aging factors (AF) of nine soils aged over 7-168 days were calculated as 3.54-8.03. The regression equation AF = 0.923 pH - 0.812 (n = 9, adjust-r2 = 0.687, P = 0.004) indicated that pH was the primary soil factor explaining 85.2% of the variance in the aging process of exogenous Sb(III). No significant toxicity was observed in soils contaminated with exogenous pentavalent Sb after 7 days of aging. These findings could provide guidance for the adjustment of Sb toxicity data, the revision of soil environmental quality standard, and efficient soil environmental management.

Biosynthetic selenium nanoparticles (Bio-SeNPs) mitigate the toxicity of antimony (Sb) in rice (Oryza sativa L.) by limiting Sb uptake, improving antioxidant defense system and regulating stress-related gene expression.

Nanotechnology offers a promising and innovative approach to mitigate biotic and abiotic stress in crop production. In this study, the beneficial role and potential detoxification mechanism of biogenic selenium nanoparticles (Bio-SeNPs) prepared from Psidium guajava extracts in alleviating antimony (Sb) toxicity in rice seedlings (Oryza sativa L.) were investigated. The results revealed that exogenous addition of Bio-SeNPs (0.05 g/L) into the hydroponic-cultured system led to a substantial enhancement in rice shoot height (73.3%), shoot fresh weight (38.7%) and dry weight (28.8%) under 50 µM Sb(III) stress conditions. Compared to Sb exposure alone, hydroponic application of Bio-SeNPs also greatly promoted rice photosynthesis, improved cell viability and membrane integrity, reduced reactive oxygen species (ROS) levels, and increased antioxidant activities. Meanwhile, exogenous Bio-SeNPs application significantly lowered the Sb accumulation in rice roots (77.1%) and shoots (35.1%), and reduced its root to shoot translocation (55.3%). Additionally, Bio-SeNPs addition were found to modulate the subcellular distribution of Sb and the expression of genes associated with Sb detoxification in rice, such as OsCuZnSOD2, OsCATA, OsGSH1, OsABCC1, and OsWAK11. Overall, our findings highlight the great potential of Bio-SeNPs as a promising alternative for reducing Sb accumulation in crop plants and boosting crop production under Sb stress conditions.

The alleviating effects and underlying mechanisms of exogenous selenium on both Sb(III) and Sb(V) toxicity in rice seedlings (Oryza sativa L.).

Selenium (Se) has been used to detoxify various heavy metals in plants. However, the effects and underlying mechanisms of exogenous Se application on the toxicity of antimonite [Sb(III)] and antimonate [Sb(V)] in crops are still poorly understood. Therefore, the potential alleviating roles of Se on the plant growth, antioxidant system, uptake and subcellular distribution of Sb, and expression of Sb-related genes were comprehensively investigated in rice seedlings (Oryza sativa L.) under both Sb(III) and Sb(V) stress conditions. The results showed that high concentrations of Sb(III) (100 µM) and Sb(V) (300 µM) caused a significant decrease in plant growth parameters, photosynthetic pigments and relative water content in rice seedlings. In contrast, the addition of Se (20 or 2 µM) improved rice growth, decreased Sb accumulation, and reduced oxidative stress in rice seedlings when exposed to 100 µM Sb(III) and 300 µM Sb(V), respectively. Furthermore, Se application could effectively improve the physiological adaptability of rice seedlings under Sb(III) and Sb(V) stress by regulating enzymatic and non-enzymatic antioxidant systems, Sb subcellular distribution and transcription levels of Sb-related genes, including in antioxidant response (OsCuZnSOD2, OsCATA and OsGSH1), detoxification (OsPCS1, OsPCS2 and OsABCC1) and Sb transport and sequestration (OsLsi1 and OsWAK11). Moreover, we also discovered that the mitigation effect of Se was dose-dependent and depended on Sb valence states. Thus, these findings contribute to our understanding of the mechanisms underlying Se-Sb antagonism in rice, offering a potentially useful method for producing both safe and Se-rich crops.

Cardiovascular Effects of Environmental Metal Antimony: Redox Dyshomeostasis as the Key Pathogenic Driver.

Significance: Cardiovascular diseases (CVDs) are the leading cause of death worldwide, which may be due to sedentary lifestyles with less physical activity and over nutrition as well as an increase in the aging population; however, the contribution of pollutants, environmental chemicals, and nonessential metals to the increased and persistent CVDs needs more attention and investigation. Among environmental contaminant nonessential metals, antimony has been less addressed. Recent Advances: Among environmental contaminant nonessential metals, several metals such as lead, arsenic, and cadmium have been associated with the increased risk of CVDs. Antimony has been less addressed, but its potential link to CVDs is being gradually recognized. Critical Issues: Several epidemiological studies have revealed the significant deleterious effects of antimony on the cardiovascular system in the absence or presence of other nonessential metals. There has been less focus on whether antimony alone can contribute to the pathogenesis of CVDs and the proposed mechanisms of such possible effects. This review addresses this gap in knowledge by presenting the current available evidence that highlights the potential role of antimony in the pathogenesis of CVDs, most likely via antimony-mediated redox dyshomeostasis. Future Directions: More direct evidence from preclinical and mechanistic studies is urgently needed to evaluate the possible roles of antimony in mitochondrial dysfunction and epigenetic regulation in CVDs. Antioxid. Redox Signal. 38, 803-823.

Toxic Elements in Traditional Kohl-Based Eye Cosmetics in Spanish and German Markets.

Kohl is a traditional cosmetic widely used in Asia and Africa. In recent years, demand for kohl-based eyelids and lipsticks has increased in Europe, linked to migratory phenomena of populations from these continents. Although the European legislation prohibits the use of heavy metals in cosmetics due to the harmful effects to human health, particularly to pregnant women and children, these elements are still present in certain products. The European Union recommended levels are Pb < 20 ppm, As < 5 ppm, Cd < 5 ppm, Sb < 100 ppm, and Ni < 200 ppm. In Germany, levels are more restrictive: Pb < 2 ppm, As < 0.5 ppm, Cd < 0.1 ppm, Sb < 0.5 ppm, and Ni < 10 ppm. Here, we analyzed 12 kohl-based cosmetics in different presentations (powder, paste, and pencil) that were purchased in Spanish and German local shops. An inductively coupled plasma optical emission spectrophotometer was used to identify toxic elements and heavy metals. Levels of Pb ranged between 1.7 and 410,000 ppm in six of the study samples, four of which had levels above the recommended limit of at least two heavy metals. Arsenic (a carcinogenic element) values were within the range allowed by the EU in only 58% of the studied samples. Moreover, two products doubled this limit, reaching levels of 9.2 and 12.6 ppm. In one of the products, cadmium, related to toxic keratitis, was four times higher (20.7 ppm) than that allowed, while in two other products, these limits were doubled (11.8 and 12.7 ppm). Our results indicate the need to supervise the manufacture of kohl-based traditional products and the analysis of their composition prior distribution in European countries.

Effects of soil properties and long aging time on the toxicity of exogenous antimony to soil-dwelling springtail Folsomia candida.

The most existing studies on the toxicity of antimony (Sb) were performed in limited types of soil and after short aging time. Effects of soil properties and long aging time on chronic toxicity of Sb(III) and Sb(V) to model organism Folsomia candida were studied in the laboratory studies. The results showed that after the Sb(V)-treated soils were aged for 365 d, the Sb exhibited no toxicity to survival and reproduction even at the nominal highest concentration of 12,800 mg kg-1 in ten types of soils with distinct differences in soil properties. In the Sb(III)-treated ten soils aged only for 30 d, the concentrations causing 50% mortality (LC50) and concentrations inhibiting 50% reproduction (EC50) were 1288-3219 mg kg-1 and 683-1829 mg kg-1, respectively. The LC50 were higher than the highest test concentration and the EC50 significantly increased by 2.24-6.16 fold after the Sb(III)-treated soils were aged for 150 d, and soil pH was the most important single factor explaining the variance in aging effects. After the aging time was 365 d, similar with Sb(V)-treated soils, no toxicity were observed in the most Sb(III)-treated soils, indicating the increasing aging effects with aging time. Regression analysis indicated that the OM and pH were the most important single factor predicting Sb toxicity to reproduction in Sb(III)-treated soils aged for 30 and 150 d, respectively.

The potential role of brassinosteroids (BRs) in alleviating antimony (Sb) stress in Arabidopsis thaliana.

Brassinosteroids (BRs) play a crucial role in improving plant resistance to various environmental stresses. In this study, we aimed to explore the potential role of BRs in protecting plants from antimony (Sb) toxicity. In the in vitro agar-plate culture experiments, the level changes of BR in wide-type plants and BR biosynthesis mutant dwrf4-1 significantly affected the corresponding response of Arabidopsis to Sb stress. Increasing the BR content significantly enhanced Sb-induced root growth inhibition and lowering the BR level appeared to reduce the plant sensitivity to Sb stress. Foliar application of eBL, however, significantly decreased the Sb accumulation and peroxidation of membrane lipids, increased the contents of chlorophyll and proline, and further boosted and strengthened the antioxidant enzymes activities. These experiments demonstrated that BRs played an important role in regulating heavy metal stress responses in plants and exogenous foliar spray of eBL was an important method for alleviating toxicity of Sb.

Effect of iron plaque on antimony uptake by rice (Oryza sativa L.).

Although iron (Fe) plaque has been shown to significantly affect the uptake of toxic antimony (Sb) by rice, knowledge about the influence of iron plaque on antimony (Sb) (amount, mechanisms, etc) is, however, limited. Here, the effect of Fe plaque on Sb(III) and Sb(V) (nominal oxidation states) uptake by rice (Oryza sativa L.) was investigated using hydroponic experiments and synchrotron-based techniques. The results showed that iron plaque immobilized Sb on the surface of rice roots. Although the binding capacity of iron plaque for Sb(III) was markedly greater than that for Sb(V), significantly more Sb(III) was taken up by roots and transported to shoots. In the presence of Fe plaque, Sb uptake into rice roots was significantly reduced, especially for Sb(III). However, this did not translate into decreasing Sb concentrations in rice shoots and even increased shoot Sb concentrations during high Fe-Sb(III) treatment.