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1.
Toxicology ; 502: 153726, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38191021

RESUMO

Heavy metals are found naturally in our environment and have many uses and applications in daily life. However, high concentrations of metals may be a result of pollution due to industrialization. In particular, cadmium (Cd), a white metal abundantly distributed in the terrestrial crust, is found in mines together with zinc, which accumulates after volcanic eruption or is found naturally in the sea and earth. High levels of Cd have been associated with disease. In the human body, Cd accumulates in two ways: via inhalation or consumption, mainly of plants or fish contaminated with high concentrations. Several international organizations have been working to establish the limit values of heavy metals in food, water, and the environment to avoid their toxic effects. Increased Cd levels may induce kidney, liver, or neurological diseases. Cd mainly accumulates in the kidney, causing renal disease in people exposed to moderate to high levels, which leads to the development of end-stage chronic kidney disease or death. The aim of this review is to provide an overview of Cd-induced nephrotoxicity, the mechanisms of Cd damage, and the current treatments used to reduce the toxic effects of Cd exposure.


Assuntos
Cádmio , Metais Pesados , Humanos , Animais , Cádmio/toxicidade , Metais Pesados/toxicidade , Rim , Fígado , Zinco/farmacologia
2.
Toxicol Lett ; 344: 26-33, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33689780

RESUMO

Cylindrospermopsin (CYN) has been involved in cases of poisoning in humans following ingestion. Studies have demonstrated that the kidney is the most affected organ. CYN exposure leads to low-molecular-weight proteinuria and increased excretions of the tubular enzymes in mice, suggesting the damage caused by CYN is mainly tubular. However, the mechanism involved in CYN nephrotoxicity remains unknown. Thus, in order to evaluate the effects of CYN exposure (0.1, 0.5 and 1.0 µg/mL) on tubular renal cells LLC-PK1 distinct mechanisms were analyzed by assessing cell death using flow cytometry, albumin uptake by fluorescence analysis, Na+/K+-ATPase activity by a colorimetric method, RT-qPCR of genes related to tubular transport and function as well as internalization of CYN by ELISA. In this study, CYN was found to induce necrosis in all concentrations. CYN also decreased albumin uptake as well as downregulated megalin and dab2 expression, both proteins involved in albumin endocytosis process. Moreover, CYN appears to be internalized by renal tubular cells through a receptor-mediated endocytosis. Finally, the present study demonstrates that CYN is responsible for disrupting tubular cell transport and function in LLC-PK1 cells.


Assuntos
Alcaloides/farmacologia , Células Epiteliais/efeitos dos fármacos , Túbulos Renais Proximais/citologia , Albuminas/metabolismo , Animais , Transporte Biológico/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Linhagem Celular , Toxinas de Cianobactérias , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Sódio/metabolismo , ATPase Trocadora de Sódio-Potássio/genética , ATPase Trocadora de Sódio-Potássio/metabolismo , Suínos
3.
Toxicol Appl Pharmacol ; 352: 97-106, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29800643

RESUMO

Fluoride (F) is a toxicant widely distributed in the environment. Experimental studies have shown kidney toxicity from F exposure. However, co-exposure to arsenic (As) has not been considered, and epidemiological information remains limited. We evaluated the association between F exposure and urinary kidney injury biomarkers and assessed As co-exposure interactions. A cross-sectional study was conducted in 239 adults (18-77 years old) from three communities in Chihuahua, Mexico. Exposure to F was assessed in urine and drinking water, and As in urine samples. We evaluated the urinary concentrations of albumin (ALB), cystatin-C (Cys-C), kidney injury molecule 1 (KIM-1), clusterin (CLU), osteopontin (OPN), and trefoil factor 3 (TFF-3). The estimated glomerular filtration rate (eGFR) was calculated using serum creatinine (Creat) levels. We observed a positive correlation between water and urine F concentrations (ρ = 0.7419, p < 0.0001), with median values of 1.5 mg/L and 2 µg/mL, respectively, suggesting that drinking water was the main source of F exposure. The geometric mean of urinary As was 18.55 ng/mL, approximately 39% of the urine samples had As concentrations above the human biomonitoring value (15 ng/mL). Multiple linear regression models demonstrated a positive association between urinary F and ALB (ß = 0.56, p < 0.001), Cys-C (ß = 0.022, p = 0.001), KIM-1 (ß = 0.048, p = 0.008), OPN (ß = 0.38, p = 0.041), and eGFR (ß = 0.49, p = 0.03); however, CLU (ß = 0.07, p = 0.100) and TFF-3 (ß = 1.14, p = 0.115) did not show significant associations. No interaction with As exposure was observed. In conclusion, F exposure was related to the urinary excretion of early kidney injury biomarkers, supporting the hypothesis of the nephrotoxic role of F exposure.


Assuntos
Arsênio/efeitos adversos , Exposição Ambiental/efeitos adversos , Fluoretos/efeitos adversos , Nefropatias/induzido quimicamente , Rim/efeitos dos fármacos , Poluentes Químicos da Água/efeitos adversos , Adolescente , Adulto , Idoso , Albuminúria/induzido quimicamente , Albuminúria/diagnóstico , Albuminúria/urina , Arsênio/urina , Biomarcadores/urina , Clusterina/urina , Estudos Transversais , Cistatina C/urina , Monitoramento Ambiental/métodos , Feminino , Fluoretos/urina , Taxa de Filtração Glomerular/efeitos dos fármacos , Receptor Celular 1 do Vírus da Hepatite A/análise , Humanos , Rim/metabolismo , Rim/fisiopatologia , Nefropatias/diagnóstico , Nefropatias/fisiopatologia , Nefropatias/urina , Masculino , México , Pessoa de Meia-Idade , Osteopontina/urina , Valor Preditivo dos Testes , Medição de Risco , Fator Trefoil-3/urina , Poluentes Químicos da Água/urina , Adulto Jovem
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