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PLoS One ; 18(1): e0279893, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36598904


Arsenic is a potent environmental toxicant and human carcinogen. Skin lesions are the most common manifestations of chronic exposure to arsenic. Advanced-stage skin lesions, particularly hyperkeratosis have been recognized as precancerous diseases. However, the underlying mechanism of arsenic-induced skin lesions remains unknown. Periostin, a matricellular protein, is implicated in the pathogenesis of many forms of skin lesions. The objective of this study was to examine whether periostin is associated with arsenic-induced skin lesions. A total of 442 individuals from low- (n = 123) and high-arsenic exposure areas (n = 319) in rural Bangladesh were evaluated for the presence of arsenic-induced skin lesions (Yes/No). Participants with skin lesions were further categorized into two groups: early-stage skin lesions (melanosis and keratosis) and advanced-stage skin lesions (hyperkeratosis). Drinking water, hair, and nail arsenic concentrations were considered as the participants' exposure levels. The higher levels of arsenic and serum periostin were significantly associated with skin lesions. Causal mediation analysis revealed the significant effect of arsenic on skin lesions through the mediator, periostin, suggesting that periostin contributes to the development of skin lesions. When skin lesion was used as a three-category outcome (none, early-stage, and advanced-stage skin lesions), higher serum periostin levels were significantly associated with both early-stage and advanced-stage skin lesions. Median (IQR) periostin levels were progressively increased with the increasing severity of skin lesions. Furthermore, there were general trends in increasing serum type 2 cytokines (IL-4, IL-5, IL-13, and eotaxin) and immunoglobulin E (IgE) levels with the progression of the disease. The median (IQR) of IL-4, IL-5, IL-13, eotaxin, and IgE levels were significantly higher in the early-and advanced-stage skin lesions compared to the group of participants without skin lesions. The results of this study suggest that periostin is implicated in the pathogenesis and progression of arsenic-induced skin lesions through the dysregulation of type 2 immune response.

Arsênio , Ceratose Actínica , Dermatopatias , Humanos , Arsênio/toxicidade , Arsênio/análise , Interleucina-13 , Interleucina-4 , Interleucina-5 , Exposição Ambiental , Abastecimento de Água , Dermatopatias/induzido quimicamente , Imunoglobulina E/efeitos adversos
Toxicol Appl Pharmacol ; 420: 115532, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33845054


Limited information is available regarding the effects of arsenic exposure on immune function. We have recently reported that chronic exposure to As was associated asthma, as determined by spirometry and respiratory symptoms. Because T helper 2 (Th2)-driven immune responses are implicated in the pathogenesis of allergic diseases, including asthma, we studied the associations of serum Th1 and Th2 mediators with the As exposure markers and the features of asthma among individuals exposed to As. A total of 553 blood samples were selected from the same study subjects recruited in our previous asthma study. Serum levels of Th1 and Th2 cytokines were analyzed by immunoassay. Subjects' arsenic exposure levels (drinking water, hair and nail arsenic concentrations) were determined by inductively coupled plasma mass spectroscopy. Arsenic exposure levels of the subjects showed significant positive associations with serum Th2-mediators- interleukin (IL)-4, IL-5, IL-13, and eotaxin without any significant changes in Th1 mediators- interferon-γ and tumor necrosis factor-α. The ratios of Th2 to Th1 mediators were significantly increased with increasing exposure to As. Notably, most of the Th2 mediators were positively associated with serum levels of total immunoglobulin E and eotaxin. The serum levels of Th2 mediators were significantly higher in the subjects with asthma than those without asthma. The results of our study suggest that the exacerbated Th2-driven immune responses are involved in the increased susceptibility to allergic asthma among individuals chronically exposed to As.

Arsênio/efeitos adversos , Asma/induzido quimicamente , Citocinas/sangue , Células Th1/efeitos dos fármacos , Equilíbrio Th1-Th2/efeitos dos fármacos , Células Th2/efeitos dos fármacos , Poluentes Químicos da Água/efeitos adversos , Adolescente , Adulto , Asma/diagnóstico , Asma/imunologia , Asma/metabolismo , Bangladesh , Carga Corporal (Radioterapia) , Estudos Transversais , Feminino , Humanos , Imunoglobulina E/sangue , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Células Th1/imunologia , Células Th1/metabolismo , Células Th2/imunologia , Células Th2/metabolismo , Adulto Jovem
Artigo em Inglês | MEDLINE | ID: mdl-34574656


Skeletal muscle mass reduction has been implicated in insulin resistance (IR) that promotes cardiometabolic diseases. We have previously reported that arsenic exposure increases IR concomitantly with the reduction of skeletal muscle mass among individuals exposed to arsenic. The arsenic methylation capacity is linked to the susceptibility to some arsenic exposure-related diseases. However, it remains unknown whether the arsenic methylation capacity affects the arsenic-induced reduction of muscle mass and elevation of IR. Therefore, this study examined the associations between the arsenic methylation status and skeletal muscle mass measures with regard to IR by recruiting 437 participants from low- and high-arsenic exposure areas in Bangladesh. The subjects' skeletal muscle mass was estimated by their lean body mass (LBM) and serum creatinine levels. Subjects' drinking water arsenic concentrations were positively associated with total urinary arsenic concentrations and the percentages of MMA, as well as inversely associated with the percentages of DMA and the secondary methylation index (SMI). Subjects' LBM and serum creatinine levels were positively associated with the percentage of DMA and SMI, as well as inversely associated with the percentage of MMA. HOMA-IR showed an inverse association with SMI, with a confounding effect of sex. Our results suggest that reduced secondary methylation capacity is involved in the arsenic-induced skeletal muscle loss that may be implicated in arsenic-induced IR and cardiometabolic diseases.

Arsênio , Arsenicais , Arsênio/análise , Arsênio/toxicidade , Exposição Ambiental/estatística & dados numéricos , Humanos , Metilação , Músculo Esquelético
Environ Int ; 143: 105890, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32619914


BACKGROUND: Alargebodyof evidence has shown a link between arsenic exposure and diabetes, but the underlying mechanisms have not yet been clarified. OBJECTIVE: We explored the association between arsenic exposure and the reduction of skeletal muscle mass as a potential mechanism of insulin resistance for developing arsenic-related hyperglycemia. METHODS: A total of 581 subjects were recruited from arsenic-endemic and non-endemic areas in Bangladesh and their fasting blood glucose (FBG), serum insulin, and serum creatinine levels were determined. Subjects' arsenic exposure levels were assessed by arsenic concentrations in water, hair, and nails. HOMA-IR and HOMA-ß were used to calculate insulin resistance and ß-cell dysfunction, respectively. Serum creatinine levels and lean body mass (LBM) were used as muscle mass indicators. RESULTS: Water, hair and nail arsenic concentrations showed significant positive associations with FBG, serum insulin and HOMA-IR and inverse associations with serum creatinine and LBM in a dose-dependent manner both in males and females. Water, hair and nail arsenic showed significant inverse associations with HOMA-ß in females but not in males. FBG and HOMA-IR were increased with the decreasing levels of serum creatinine and LBM. Odds ratios (ORs)of hyperglycemia were significantly increased with the increasing concentrations of arsenic in water, hair and nails and with the decreasing levels of serum creatinine and LBM. Females' HOMA-IR showed greater susceptibility to the reduction of serum creatinine and LBM, possibly causing the greater risk of hyperglycemia in females than males. Path analysis revealed the mediating effect of serum creatinine level on the relationship of arsenic exposure with HOMA-IR and hyperglycemia. CONCLUSION: Arsenic exposure elevates FBG levels and the risk of hyperglycemia through increasing insulin resistance with greater susceptibility in females than males. Additionally, arsenic exposure-related reduction of skeletal muscle mass may be a mechanism underlying the development of insulin resistance and hyperglycemia.

Arsênio , Hiperglicemia , Resistência à Insulina , Arsênio/análise , Arsênio/toxicidade , Bangladesh , Glicemia , Estudos Transversais , Feminino , Humanos , Hiperglicemia/induzido quimicamente , Masculino , Músculo Esquelético/química
Environ Int ; 131: 105029, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31352261


BACKGROUND: Arsenic poisoning is a public health problem worldwide. A few studies have reported the effects of arsenic exposure on adult cognitive function, but with limitations in the subject selection and exposure markers. Moreover, information regarding the association between arsenic exposure and biomarker of cognitive impairment is scarce. OBJECTIVES: We examined the associations between arsenic exposure and adult cognitive impairment using the Mini-Mental State Examination (MMSE) and the serum levels of brain-derived neurotrophic factor (BDNF), a potential biomarker of cognitive health status. METHODS: We designed a cross-sectional study that recruited 693 adult (18-60 years old) subjects from the areas of low- and high­arsenic exposure in rural Bangladesh. The subjects' arsenic exposure levels (drinking water, hair, and nail arsenic concentrations) were measured by inductively coupled plasma-mass spectroscopy. The Bangla version of the MMSE was used as a cognitive assessment tool. Serum BDNF (sBDNF) levels were assessed by immunoassay. RESULTS: In this study, we found that average MMSE score and sBDNF level of the subjects in arsenic-endemic areas were significantly (p < 0.001 for both) lower than those of the subjects in non-endemic area. Our analyses revealed that both MMSE scores and sBDNF levels were decreased with the increasing concentrations of arsenic in drinking water, hair, and nails in a dose-dependent fashion. In regression analyses, significant associations of arsenic exposure metrics with MMSE scores and sBDNF levels were observed even after adjustment for several variables. Intriguingly, MMSE scores showed a significantly positive correlation with sBDNF levels. CONCLUSION: Our findings demonstrate that chronic exposure to arsenic dose-dependently decreases cognitive function in adults, with a concomitant reduction of sBDNF levels. A decreased BDNF level may be part of the biochemical basis of chronic arsenic exposure-related cognitive impairment.

Arsênio/toxicidade , Fator Neurotrófico Derivado do Encéfalo/sangue , Disfunção Cognitiva/induzido quimicamente , Poluentes Químicos da Água/toxicidade , Adolescente , Adulto , Arsênio/análise , Bangladesh , Biomarcadores/sangue , Estudos Transversais , Água Potável/química , Feminino , Cabelo/química , Humanos , Masculino , Pessoa de Meia-Idade , Unhas/química , Poluentes Químicos da Água/análise , Adulto Jovem