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.

Single-cell RNA sequencing analysis to evaluate antimony exposure effects on cell-lineage communications within the Drosophila testicular niche.

The increasing production and prevalence of antimony (Sb)-related products raise concerns regarding its potential hazards to reproductive health. Upon environmental exposure, Sb reportedly induces testicular toxicity during spermatogenesis; moreover, it is known to affect various testicular cell populations, particularly germline stem cell populations. However, the cell-cell communication resulting from Sb exposure within the testicular niche remains poorly understood. To address this gap, herein we analyzed testicular single-cell RNA sequencing data from Sb-exposed Drosophila. Our findings revealed that the epidermal growth factor receptor (EGFR) and WNT signaling pathways were associated with the stem cell niche in Drosophila testes, which may disrupt the homeostasis of the testicular niche in Drosophila. Furthermore, we identified several ligand-receptor pairs, facilitating the elucidation of intercellular crosstalk involved in Sb-mediated reproductive toxicology. We employed scRNA-seq analysis and conducted functional verification to investigate the expression patterns of core downstream factors associated with EGFR and WNT signatures in the testes under the influence of Sb exposure. Altogether, our results shed light on the potential mechanisms of Sb exposure-mediated testicular cell-lineage communications.

Integrated physiological, intestinal microbiota, and metabolomic responses of adult zebrafish (Danio rerio) to subacute exposure to antimony at environmentally relevant concentrations.

The available information regarding the impact of antimony (Sb), a novel environmental pollutant, on the intestinal microbiota and host health is limited. In this study, we conducted physiological characterizations to investigate the response of adult zebrafish to different environmental concentrations (0, 30, 300, and 3000 µg/L) of Sb over a period of 14 days. Biochemical and pathological changes demonstrated that Sb effectively compromised the integrity of the intestinal physical barrier and induced inflammatory responses as well as oxidative stress. Analysis of both intestinal microbial community and metabolome revealed that exposure to 0 and 30 µg/L of Sb resulted in similar microbiota structures; however, exposure to 300 µg/L altered microbial communities' composition (e.g., a decline in genus Cetobacterium and an increase in Vibrio). Furthermore, exposure to 300 µg/L significantly decreased levels of bile acids and glycerophospholipids while triggering intestinal inflammation but activating self-protective mechanisms such as antibiotic presence. Notably, even exposure to 30 µg/L of Sb can trigger dysbiosis of intestinal microbiota and metabolites, potentially impacting fish health through the "microbiota-intestine-brain axis" and contributing to disease initiation. This study provides valuable insights into toxicity-related information concerning environmental impacts of Sb on aquatic organisms with significant implications for developing management strategies.

Tracing toxic path of antimony: From bioaccumulation to DNA hypomethylation in zebrafish (Danio rerio).

The increasing concentration of Antimony (Sb) in ecological environments has raised serious concerns about its potential biotoxicological impact. This study investigated the toxicokinetics, Global DNA Methylation (GDM), biomarker expression, and Integrated Biological Response (IBR) of Sb at different concentrations in zebrafish. The toxic mechanism of Sb exposure was simulated using molecular dynamics (MD). The results showed that significant differences effect existed (BCFk: liver > ovary > gut > brain) and uptake saturation phenomenon of Sb among zebrafish tissues. Over a 54-day exposure period, the liver emerged as the main target site for Sb-induced GDM, and the restoration was slower than in other tissues during the 54-day recovery period. Moreover, the concentration of Sb had a significant impact on the normally expression of biomarkers, with GSTM1 inhibited and MTF2, MT1, TET3, and p53 showing varying degrees of activation at different Sb concentrations. This could be attributed to Sb3+ potentially occupying the active site or tightly binding to the deep cavity of these genes. The IBR and MD results highlighted DNMT1 as the most sensitive biomarker among those assessed. This heightened sensitivity can be attributed to the stable binding of Sb3+ to DNMT1, resulting in alterations in the conformation of DNMT1's catalytic domain and inhibition of its activity. Consequently, this disruption leads to damage to the integrity of GDM. The study suggests that DNA methylation could serve as a valuable biomarker for assessing the ecotoxicological impact of Sb exposure. It contributes to a better understanding of the toxicity mechanisms in aquatic environments caused potential pollutants.

A review on sources of soil antimony pollution and recent progress on remediation of antimony polluted soils.

Antimony (Sb) is a serious toxic and non-essential metalloid for animals, humans, and plants. The rapid increase in anthropogenic inputs from mining and industrial activities, vehicle emissions, and shoot activity increased the Sb concentration in the environment, which has become a serious concern across the globe. Hence, remediation of Sb-contaminated soils needs serious attention to provide safe and healthy foods to humans. Different techniques, including biochar (BC), compost, manures, plant additives, phyto-hormones, nano-particles (NPs), organic acids (OA), silicon (Si), microbial remediation techniques, and phytoremediation are being used globally to remediate the Sb polluted soils. In the present review, we described sources of soil Sb pollution, the environmental impact of antimony pollution, the multi-faceted nature of antimony pollution, recent progress in remediation techniques, and recommendations for the remediation of soil Sb-pollution. We also discussed the success stories and potential of different practices to remediate Sb-polluted soils. In particular, we discussed the various mechanisms, including bio-sorption, bio-accumulation, complexation, and electrostatic attraction, that can reduce the toxicity of Sb by converting Sb-V into Sb-III. Additionally, we also identified the research gaps that need to be filled in future studies. Therefore, the current review will help to develop appropriate and innovative strategies to limit Sb bioavailability and toxicity and sustainably manage Sb polluted soils hence reducing the toxic effects of Sb on the environment and human health.

Effects of antimony stress on growth, structure, enzyme activity and metabolism of Nipponbare rice (Oryza sativa L.) roots.

Some antimony (Sb) contaminated areas are used for rice cultivation in response to economic demands. However, little is known about the effects of Sb stress on the growth and metabolism of rice roots. Thus, a hydroponic experiment was carried out on the growth, root anatomy, enzyme activity, and metabolism of Nipponbare rice (Oryza sativa L. ssp. japonica cv. Nipponbare) under varying levels of Sb (III) stress (0 mg L-1, 10 mg L-1, and 50 mg L-1). With the increase of Sb concentration, rice root length and root fresh weight declined by 67.8 % and 90.5 % for 10 mg L-1 Sb stress and 94.1 % and 98.4 % for 50 mg L-1 Sb stress, respectively. Anatomical analysis of cross-sections of Sb-treated roots showed an increase in cell wall thickness and an increase in the number of cell mitochondria. The 10 mg L-1 and 50 mg L-1 Sb stress increased the activity of enzyme superoxide dismutase (SOD) in root cells by 1.94 and 2.40 times, respectively. Compared to the control, 10 mg L-1 Sb treatment increased the activity of catalase (CAT) and peroxidase (POD), as well as the concentrations of antioxidant glutathione (GSH) in the root by 1.46, 1.38, and 0.52 times, respectively. However, 50 mg L-1 Sb treatment significantly decreased the activity or content of CAT, POD and GSH by 28.1 %, 13.5 % and 28.2 %, respectively. Nontargeted LC/MS-based metabolomics analysis identified 23 and 13 significantly differential metabolites in rice roots exposed to 10 mg L-1 and 50 mg L-1 Sb, respectively, compared to the control. These differential metabolites were involved in four main metabolic pathways including the tricarboxylic acid cycle (TCA cycle), butanoate metabolism, alanine, aspartate and glutamate metabolism, and alpha-linolenic acid metabolism. Taken together, these findings indicate that Sb stress destroys the structure of rice roots, changes the activity of enzymes, and affects the metabolic pathway, thereby reducing the growth of rice roots and leading to toxicity.

Short-term exposure to antimony induces hepatotoxicity and metabolic remodeling in rats.

Antimony (Sb) poses a significant threat to human health due to sharp increases in its exploitation and application globally, but few studies have explored the pathophysiological mechanisms of acute hepatotoxicity induced by Sb exposure. We established an in vivo model to comprehensively explore the endogenous mechanisms underlying liver injury induced by short-term Sb exposure. Adult female and male Sprague-Dawley rats were orally administrated various concentrations of potassium antimony tartrate for 28 days. After exposure, the serum Sb concentration, liver-to-body weight ratio, and serum glucose levels significantly increased in a dose-dependent manner. Body weight gain and serum concentrations of biomarkers of hepatic injury (e.g., total cholesterol, total protein, alkaline phosphatase, and the aspartate aminotransferase/alanine aminotransferase ratio) decreased with increasing Sb exposure. Through integrative non-targeted metabolome and lipidome analyses, alanine, aspartate, and glutamate metabolism; phosphatidylcholines; sphingomyelins; and phosphatidylinositols were the most significantly affected pathways in female and male rats exposed to Sb. Additionally, correlation analysis showed that the concentrations of certain metabolites and lipids (e.g., deoxycholic acid, N-methylproline, palmitoylcarnitine, glycerophospholipids, sphingomyelins, and glycerol) were significantly associated with hepatic injury biomarkers, indicating that metabolic remodeling may be involved in apical hepatotoxicity. Our study demonstrated that short-term exposure to Sb induces hepatotoxicity, possibly through a glycolipid metabolism disorder, providing an important reference for the health risks of Sb pollution.

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.

Acute effects of antimony exposure on adult zebrafish (Danio rerio): From an oxidative stress and intestinal microbiota perspective.

The rapid development of the textile industry has resulted in a large influx of wastewater production. The "national discharge standards of water pollutants for dyeing and finishing of textile industry (GB4287-2012)" stipulates that the discharge of total Sb from textile industry effluent must be < 0.10 mg/L, but it is difficult to meet the standard at present. Antimony is potentially carcinogenic, and the pathogenic mechanism of antimony is poorly understood. In this study, the acute toxic effects of various concentrations of antimony on adult zebrafish (Danio rerio) were investigated, including effects on oxidative stress, neurotransmitters and intestinal microbiota. The activities of catalase (CAT), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), superoxide dismutase (SOD), total antioxidant capacity (T-AOC) and acetylcholinesterase (AChE) were measured in zebrafish muscle and intestine tissue samples. In addition, intestinal microbial community composition and diversity of zebrafish were also analyzed. The results demonstrated that SOD, CAT and GSH-Px activities in the zebrafish gut showed a decreasing and then increasing trend with antimony concentration increasing. SOD, CAT and MDA in zebrafish muscle decreased with increasing exposure time. GSH-Px activities increased with increasing exposure time. T-AOC increased and then decreased. In addition, antimony exposure was neurotoxic to zebrafish, and a significant decrease in AChE activity was found in the intestine with increased exposure time. The neurotoxicity caused by antimony in the high concentration group (40 mg/L) was stronger than that in low concentration groups (10 mg/L and 20 mg/L). Notably, antimony exposure caused increases in the relative abundance of phyla Fusobacteriota and Actinomycetes, but decreases in the relative abundance of the phyla Firmicutes and Proteobacteria in zebrafish intestine. These outcomes will advance our understanding of antimony-induced biotoxicity, environmental problems, and health hazards. In conclusion, this study shows that acute exposure of antimony to zebrafish induces host oxidative stress and neurotoxicity, dysregulates the intestinal microbiota, showing adverse effects on the health and gut microbiota of zebrafish.

Combined exposure to multiple metals on cardiovascular disease in NHANES under five statistical models.

BACKGROUND: It is well-documented that heavy metals are associated with cardiovascular disease (CVD). However, there is few studies exploring effect of metal mixture on CVD. Therefore, the primary objective of present study was to investigate the joint effect of heavy metals on CVD and to identify the most influential metals in the mixture. METHODS: Original data for study subjects were obtained from the National Health and Nutrition Examination Survey. In this study, adults with complete data on 12 kinds of urinary metals (antimony, arsenic, barium, cadmium, cobalt, cesium, molybdenum, mercury, lead, thallium, tungsten, and uranium), cardiovascular disease, and core covariates were enrolled. We applied five different statistical strategies to examine the CVD risk with metal exposure, including multivariate logistic regression, adaptive elastic net combined with Environmental Risk Score, Quantile g-computation, Weighted Quantile Sum regression, and Bayesian kernel machine regression. RESULTS: Higher levels of cadmium, tungsten, cobalt, and antimony were significantly associated with Increased risk of CVD when covariates were adjusted for multivariate logistic regression. The results from multi-pollutant strategies all indicated that metal mixture was positively associated with the risk of CVD. Based on the results of multiple statistical strategies, it was determined that cadmium, tungsten, cobalt, and antimony exhibited the strongest positive correlations, whereas barium, lead, molybdenum, and thallium were most associated with negative correlations. CONCLUSION: Overall, our study demonstrates that exposure to heavy metal mixture is linked to a higher risk of CVD. Meanwhile, this association may be driven primarily by cadmium, tungsten, cobalt, and antimony. Further prospective studies are warranted to validate or refute our primary findings as well as to identify other important heavy metals linked with CVD.

Disruption of mitochondrial redox homeostasis as a mechanism of antimony-induced reactive oxygen species and cytotoxicity.

Occupational and environmental Sb exposure has been associated with increased risk of respiratory diseases and lung cancer, but the toxicities and molecular mechanisms of Sb have been less investigated. In the present study, we first analyzed the Sb toxicity profile of lung adenocarcinoma A549 cells, and found that Sb dose-dependently decreased the cell viability and arrested cell cycle at G2/M but did not induce apoptosis. We next investigated the role of reactive oxygen species (ROS) involved in Sb-induced cytotoxicity. The results showed that Sb did not significantly induce cytosolic ROS production by NADPH oxidase (NOX) and the NOX inhibitors did not ameliorate the Sb-induced cell viability loss in A549 cells. However, the level of mitochondrial ROS (mtROS) was significantly increased in Sb-exposed cells and the mitochondria-targeted antioxidant significantly improved cell viability. These results suggested that mitochondria but not NOX is the major source of ROS production and mtROS plays a critical role in Sb-induced cytotoxicity. Furthermore, we found that Sb induced mitochondria dysfunction including the significant decrease of ATP level and mitochondrial membrane potential. Finally, Sb exposure decreased the activity of complex I and complex III, the level of -SH and GSH in mitochondria, and the activity of mitochondrial GR, GPx and TrxR, but increased the mitochondrial SOD activity, suggesting the disruption of mitochondrial redox homeostasis. Taken together, these findings suggested that Sb impaired mitochondrial redox homeostasis, resulting in formation of mtROS, thereby inhibited mitochondrial function and led to cytotoxicity.

Silicon alleviates antimony phytotoxicity in giant reed (Arundo donax L.).

MAIN CONCLUSION: Silicon enhances photosynthetic efficiency, biomass, and lignification of root structures possibly limiting antimony translocation and mitigating phytotoxicity in giant reed plants. Antimony (Sb) is a non-essential metalloid causing toxic effects in plants. Silicon has been reported to impart tolerance against biotic and abiotic stress in plants. Fast-growing plant, giant reed (Arundo donax L.) is a promising energy crop, can be a suitable plant for phytoremediation. However, information regarding the tolerance capacity with respect to Sb toxicity and potential of Si to mitigate the Sb phytotoxicity in giant reed are very scarce. Rhizomes of giant reed were grown for ten weeks in hydroponics exposed to Sb, Si, and their combination wherein treatment without Sb/Si served as control. Effect of these treatments on rate of net photosynthesis and photosynthetic pigments, phytoextraction ability of Sb, Si and Sb uptake, plant biomass, and lignification and suberization of roots along with localization of Sb and Si were analysed. We found that Si considerably improved the growth and biomass of giant reed under Sb toxicity. Antimony reduced the photosynthesis and decreased the content of photosynthetic pigments, which was completely alleviated by Si. Silicon amendment to Sb treated plants enhanced root lignification. Silicon enhanced lignification of root structures probably restricted the Sb translocation. However, co-localization of Sb with Si has not been observed neither at the shoot nor at the root levels. Similarly, Sb was also not detected in leaf phytoliths. These findings suggest that Si treatment promotes overall plant growth by improving photosynthetic parameters and decreasing Sb translocation from root to shoot in giant reed by improving root lignification.

Toxicity of soil antimony to earthworm Eisenia fetida (Savingy) before and after the aging process.

Information on soil antimony (Sb) toxicity to earthworm Eisenia fetida (Savingy) is limited. This ecotoxicology study was designed to quantify the soil Sb toxicity to earthworm E. fetida before and after aging process, establishing dose-effect relationship between Sb content and mortality. Results of the avoidance test and acute test showed that the values of net avoidance response, escape rate and mortality were generally decreased in aged treatment compared to that in fresh treatment, respectively from 93.33% to 66.67%, 36.67% to 13.33% and 100% to 53.33% (15 d) taking TL800 (treatment level of 800 mg/kg) for example, meanwhile the values of median lethal content (LC50) at 72 h, 7 d and 15 d were respectively increased from 355.27 mg/kg to 2324.55 mg/kg, 322.19 mg/kg and 1743.19 mg/kg and 282.74 mg/kg to 745.94 mg/kg, indicating that aging process could reduce the Sb acute toxicity to earthworm. According to a three-step sequential extraction procedure, the bioavailable Sb ranged from 24.45% to 43.24% and 16.97% to 27.70% in fresh treatment and aged treatment, respectively, and the mortality of earthworm for 24 h decreased with the decrease of the content of mild acid-soluble antimony (which decreased averagely from 23.09% to 14.00%), which was more suited to assess Sb toxicity. This is the first report that confirms the toxicity of soil Sb to earthworm E. fetida as well as the considering of aging process and speciation.

Arsenic and antimony co-induced nephrotoxicity via autophagy and pyroptosis through ROS-mediated pathway in vivo and in vitro.

Arsenic (As) and antimony (Sb) are commonly accumulated environmental pollutants that often coexist in nature and cause serious widespread biological toxicity. To investigate the nephrotoxicity induced by As and Sb in detail, we explored the mechanism by which As and Sb cotreatment induced autophagy and pyroptosis in vivo and in vitro. In this study, mice were treated with 4 mg/kg arsenic trioxide (ATO) or/and 15 mg/kg antimony trichloride (SbCl3) by intragastric intubation for 60 days. TCMK-1 cells were treated with ATO (12.5 µM), SbCl3 (25 µM) or a combination of As and Sb for 24 h. The results of the in vivo experiment demonstrated that As or/and Sb exposure could induce histopathological changes in the kidneys, and increase the levels of biochemical indicators of nephrotoxicity. In addition, As and Sb can co-induce oxidative stress, which further activate autophagy and pyroptosis. In an in vitro experiment, As and/or Sb coexposure increased ROS generation and decreased MMP. Moreover, the results of related molecular experiments further confirmed that As and Sb coactivated autophagy and pyroptosis. In conclusion, our results indicated that As and Sb co-exposure could cause autophagy and pyroptosis via the ROS pathway, and these two metals might have a synergistic effect on nephrotoxicity.

Antimony exposure promotes bladder tumor cell growth by inhibiting PINK1-Parkin-mediated mitophagy.

Antimony is one of the heavier pnictogens and is widely found in human food chains, water sources, and as an air pollutant. Recent years have seen steadily increasing concentrations of antimony in the ecological environment; critically, several studies have indicated that antimony might pose a tumorigenic risk factor in several cancers. Therefore, antimony toxicity has attracted increasing research attention, with the molecular mechanisms underlying suspected antimony-mediated tumor transformation of greatest interest. Our results showed that the serum concentration of antimony was higher in bladder tumor patients relative to levels in non-tumor patients. Moreover, that such high antimony serum concentration were closely associated with poorer outcome in bladder tumor patients. Additionally, we demonstrated that the presence of antimony promoted both in vitro and in vivo bladder tumor cell growth. Our results also indicated that low-dose antimony resulted in significantly decreased mitochondrial membrane potential, mitochondrial respiratory enzyme complex I/II/III/IV activity, ATP/ADP ratio, and ATP concentration relative to the control group. These findings suggested that antimony caused mitochondrial damage. Finally, we found that low-dose antimony(0.8uM) inhibited mitophagy by deregulating expression of PINK1, Parkin, and p(ser65)-Parkin, and activation of PINK1-Parkin pathway by CCCP could inhibit antimony-induced tumor cell growth. Collectively, this inhibited the proliferation of bladder tumor cells. Overall, our study suggested that antimony promoted bladder tumor cell growth by inhibiting PINK1-Parkin-mediated mitophagy. These findings highlight the therapeutic potential in targeting molecules within this antimony induced-PINK1/Parkin signaling pathway and may offer a new approach for the treatment of bladder cancer.

Arsenic (III) and/or Antimony (III) induced disruption of calcium homeostasis and endoplasmic reticulum stress resulting in apoptosis in mice heart.

Arsenic (As) and antimony (Sb) are known as an environmental contaminant with cardiotoxicity properties. The endoplasmic reticulum (ER) is the largest calcium reservoir in the cell, and its calcium homeostasis disorder plays a vital role in endoplasmic reticulum stress (ERS) and apoptosis. The objective of this study was to investigate whether As and Sb induced apoptosis via endoplasmic reticulum stress (ERS) linked to calcium homeostasis disturbance. In this study, thirty-two adult mice were gavage-fed daily with As2O3 (4 mg/kg), SbCl3 (15 mg/kg) and co-treat with SbCl3 (15 mg/kg) and As2O3 (4 mg/kg) daily for 60 days. It was observed that As or/and Sb caused histopathological lesions and ER expansion of the heart. Meanwhile, the gene expression of ER Ca2+ release channels (RyR2 and IP3R) and calmodulin-dependent protein kinase II (CaMKII) increased while the levels of mRNA and protein of ER Ca2+ uptake channel (SERCA2) downregulated significantly compared to the controls. Then, As or/and Sb induced ERS and triggered the ER apoptotic pathway by activating unfolded protein response (UPR)-associated genes ((PERK, ATF6, IRE1, XBP1, JNK, GRP78), and apoptosis-related genes (Caspase12, Caspase3, p53, CHOP). Above indicators in As + Sb group became more severe than that of As group and Sb group. Overall, our results proved that the cardiotoxicity caused by As or/and Sb might be concerning disturbing calcium homeostasis, which induced apoptosis through the ERS pathway.

Sensitivity of Freshwater Australian Bass (Macquaria novemaculeata) and Silver Perch (Bidyanus bidyanus) to Waterborne Antimony: Exposure-Dose-Response Characteristics and Ion Homeostasis.

We conducted acute toxicity studies using semi-static protocols to examine the lethal responses of Australian bass and silver perch exposed to antimony (Sb) oxidation states in Sb(III) (10.5-30.5 mg L-1) and Sb(V) (95.9-258.7 mg L-1). Bioavailability and the effects of Sb on body ion regulation (Na, Ca, Mg, and K) were also investigated. Antimony species-specific effects were observed with exposure to both Sb oxidation states. Median lethal concentrations (LC50s) for Sb(III) were 13.6 and 18 mg L-1 for Australian bass and silver perch, respectively, and the LC50 for Sb(V) in Australian bass was 165.3 mg L-1. The LC50 could not be calculated for silver perch exposed to Sb(V) as the maximum exposure concentrations produced 40% mortality but a larger-than value of > 258.7 mg L-1 was estimated. Relative median potency values derived from the LC50s were 0.1 Sb(III) and 12.2 and 16.6 Sb(V) for Australian bass and silver perch, respectively, demonstrating greater toxicity of Sb(III) to both fish species. Antimony uptake in fish was observed. Median critical body residue (CBR50) values of 77.7 and 26.6 mg kg-1 for Sb(III) were estimated for Australian bass and silver perch, respectively, and 628.1 mg kg-1 for Sb(V) in Australian bass. Bioconcentration factors (BCFs) for both Sb(III) and Sb(V) did not change with exposure but the greater BCFs for fish exposed to Sb(III) indicate that it is more bioavailable than Sb(V) in acute exposure. No effects on whole-body Na, Ca, Mg, or K ions were observed with fish exposure to either Sb species.

Complex Mechanisms of Antimony Genotoxicity in Budding Yeast Involves Replication and Topoisomerase I-Associated DNA Lesions, Telomere Dysfunction and Inhibition of DNA Repair.

Antimony is a toxic metalloid with poorly understood mechanisms of toxicity and uncertain carcinogenic properties. By using a combination of genetic, biochemical and DNA damage assays, we investigated the genotoxic potential of trivalent antimony in the model organism Saccharomyces cerevisiae. We found that low doses of Sb(III) generate various forms of DNA damage including replication and topoisomerase I-dependent DNA lesions as well as oxidative stress and replication-independent DNA breaks accompanied by activation of DNA damage checkpoints and formation of recombination repair centers. At higher concentrations of Sb(III), moderately increased oxidative DNA damage is also observed. Consistently, base excision, DNA damage tolerance and homologous recombination repair pathways contribute to Sb(III) tolerance. In addition, we provided evidence suggesting that Sb(III) causes telomere dysfunction. Finally, we showed that Sb(III) negatively effects repair of double-strand DNA breaks and distorts actin and microtubule cytoskeleton. In sum, our results indicate that Sb(III) exhibits a significant genotoxic activity in budding yeast.

Effect of antimony in soils of an Sb mine on the photosynthetic pigments and antioxidant system of Dittrichia viscosa leaves.

Antimony is a toxic element whose concentration in soil and water has been rising due to anthropogenic activities. This study focuses on its accumulation in leaves of Dittrichia viscosa growing in soils of an abandoned Sb mine, and the effect on oxidant/antioxidant systems and photosynthetic efficiency. The results showed leaves to have a high Sb accumulation capacity. The amount of total chlorophyll decreased depending on Sb concentration and of carotenoids increased slightly, with a consequent increase in carotenoid/chlorophyll ratio. Photosynthetic efficiency was unaffected. The amount of O 2 .- rose, although there was no increase in cell membrane damage, with lipid peroxidation levels being similar to normal. This response may be due to considerable increases that were observed in total phenolics, PPO activity, and enzymatic antioxidant system. SOD, POX, and DHAR activities increased in response to increased Sb amounts in leaves. The ascorbate/glutathione cycle was also affected, with strong increases observed in all of its components, and consequent increases in total contents of the ascorbate and glutathione pools. However, the ratio between reduced and oxidized forms declined, reflecting an imbalance between the two, especially that between GSH and GSSG. Efficient detoxification of Sb may take place either through increases in phenolics, carotenoids, and components of the glutathione-ascorbate cycle or through the enzymatic antioxidant system. Since Dittrichia viscosa accumulates large amounts of Sb without suffering oxidative damage, it could be used for phytoremediation.

Antimony and its compounds: Health impacts related to pulmonary toxicity, cancer, and genotoxicity.

Although occupational exposure to antimony and its compounds can produce pulmonary toxicity, human carcinogenic impacts have not been observed. Inhalation studies with respirable antimony trioxide particles administered to rats and mice have, however, induced carcinogenic responses in the lungs and related tissue sites. Genotoxicity studies conducted to elucidate mechanism(s) for tumor induction have produced mixed results. Antimony compounds do not induce gene mutations in bacteria or cultured mammalian cells, but chromosome aberrations and micronuclei have been observed, usually at highly cytotoxic concentrations. Indirect mechanisms of genotoxicity have been proposed to mediate these responses. In vivo genotoxicity tests have generally yielded negative results although several positive studies of marginal quality have been reported. Genotoxic effects may be related to indirect modes of action such as the generation of excessive reactive oxygen species (ROS), altered gene expression or interference with DNA repair processes. Such indirect mechanisms may exhibit dose-response thresholds. For example, interaction of ROS with in vivo antioxidant systems could yield a threshold for genotoxicity (and cancer) only at concentrations above the capacity of antioxidant defense mechanisms to control and/or eliminate damage from ROS.