Tributyltin chloride induces renal dysfunction by inflammation and oxidative stress in female rats.

Tributyltin chloride (TBT) is an organometallic pollutant that is used as a biocide in antifouling paints. TBT induces several toxic and endocrine-disrupting effects. However, studies evaluating the effects of TBT on renal function are rare. This study demonstrates that TBT exposure is responsible for improper renal function as well as the development of abnormal morphophysiology in mammalian kidneys. Female rats were treated with TBT, and their renal morphophysiology was assessed. Morphophysiological abnormalities such as decreased glomerular filtration rate and increased proteinuria levels were observed in TBT rats. In addition, increases in inflammation, collagen deposition and α-smooth muscle actin (α-SMA) protein expression were observed in TBT kidneys. A disrupted cellular redox balance and apoptosis in kidney tissue were also observed in TBT rats. TBT rats demonstrated reduced serum estrogen levels and estrogen receptor-α (ERα) protein expression in renal cortex. Together, these data provide in vivo evidence that TBT is toxic to normal renal function and that these effects may be associated with renal histopathology complications, such as inflammation and fibrosis.

Análise de especiação de estanho em plasma de trabalhadores expostos / Speciation analysis of tin in plasma of exposed workers

O estanho (Sn) é um elemento natural na crosta terrestre obtido a partir do minério cassiterita. Devido à sua utilização em processos industriais, é encontrado distribuído pelo ambiente, e sendo um potencial contaminante. Na natureza, aparece nas formas inorgânicas e orgânicas, e quanto menor a cadeia orgânica associada ao metal, maior toxicidade do composto. Compostos organoestânicos de cadeia curta, como trimetil e trietil Sn, são bem absorvidos no trato gastrointestinal. Compostos organoestânicos podem penetrar nas membranas celulares, causando danos celulares e nas mitocôndrias, e ainda interromper a fosforilação oxidativa. Desta forma, podem ser imuno e genotóxicos. O interesse na especiação dos compostos de Sn é devido à toxicidade ser dependente da espécie. O plasma sanguíneo contém a fração biodisponível do analito e pode intermediar a predição de algumas formas de toxicidade crônica. No entanto, há poucos trabalhos sobre como o Sn se encontra no plasma. Portanto, a caracterização dos constituintes que se ligam e / ou transportam esse elemento ajustam na compreensão de seu metabolismo, elucidação dos mecanismos de toxicidade, uma melhor compreensão da distribuição de Sn na célula e sua de posição nos tecidos. Neste estudo, foi desenvolvido um método analítico para separação das espécies de Sn no plasma sanguíneo de trabalhadores que beneficiam o minério de cassiterita, através de cromatografia líquida por filtração em gel, enquanto a concentração do Sn nas frações coletadas foi determinada por espectrometria de absorção atômica por forno de grafite. O uso de Sepharose CL-4B, uma coluna com altura de 1 m, fase móvel de 50 milimolares (mM) Tris-HCl + 30 mM NaHCO3, pH 7,4, fluxo de 0,7 militros por minuto (ml min-1), volumes de plasma injetado e frações coletadas iguais a 2 ml cada,apresentou melhor separação das proteínas, com o aparecimento de três picos...

Tin is a natural element in the earth's crust and is obtained from cassiterite ores. Owing to their wide use in industrial processes, tin is relatively distributed in the environment. In nature, it occurs in both inorganic and organic forms and shorter organic chainassociated to the metal, higher the toxicity of the compound. Short-chain organotin compounds such as trimethyl and triethyl tin are well absorbed in the gastrointestinal tract. Organotin compounds can penetrate cell membranes causing damage to cell andmitochondria, as well as interrupt oxidative phosphorylation. Thus organic compounds can be immunotoxic and genotoxic. The interest on speciation of the organotin compounds is due to species-dependent toxicity. The blood plasma contains the bioavailable fraction of the analyte and can mediate the prediction of some forms ofchronic toxicity. However, very few species of tin existing in the plasma are known. Therefore, the characterization of the constituents that bind to and / or transporting the element of interest is critical to full understanding of metabolism, elucidation of themechanisms of toxicity, a better understanding of the distribution of tin in the cell and its deposition in tissues. In this study, we developed an analytical method for theseparation of tin species in blood plasma using gel filtration liquid chromatography while tin concentration in the collected fractions was determined by graphite furnace atomic absorption spectrometry. The use of Sepharose CL-4B, height of 1 m, mobilephase of 50mM Tris-HCl + 30mM NaHCO3, pH 7,4, flow 0,7 ml min-1, fractions collected volume of 2 ml, plasma injected volume of 2 ml, showed the best protein separation with three peaks. For the determination of tin, pyrolisis and atomization...

Comparison of the predicted in vivo behaviour of the Sn(II)-APDDMP complex and the results as studied in a rodent model.

In a quest for more effective radiopharmaceuticals for pain palliation of metastatic bone cancer, this paper relates results obtained with ((117m)Sn labelled) Sn(II) complexed to the bone seeking bisphosphonate, N,N-dimethylenephosphonate-1-hydroxy-3-aminopropylidenediphosphonate (APDDMP). APDDMP is synthesised from the known bone cancer pain palliation agent 1-hydroxy-3-aminopropylidenediphosphonate (APD, Pamindronate). This work is performed to utilise the idea that the low bone marrow radio toxicity of (117m)Sn could afford a highly effective radiopharmaceutical in pain palliation but also in the curative treatment of bone metastasis. Complex-formation constants of APDDMP with the important blood plasma metal-ions, Ca(2+), Mg(2+), Zn(2+) as well as the added metal ion, Sn(2+) were measured by glass electrode potentiometry at 25 degrees C and I = 150 mM. Blood plasma models were constructed using the computer code ECCLES and the results compared with those gathered from tests on a rodent model. The ((117m)Sn-labelled) Sn(II)-APDDMP complex was found to have only some liver and bone uptake although a high trabecular to normal bone ratio was recorded. From the blood plasma model this was shown to be primarily due to the high affinity of APDDMP for Ca(II) causing some of the Sn(II)-APDDMP complex to dissociate. High kidney uptake and excretion as well as high bladder uptake was recorded which was shown to be due to the dissociation of the Sn(II)-APDDMP complex in blood plasma. Animal model observations could be explained by the blood plasma modelling.

[Comparison of serum trace element spectrum of liver cancer patients and healthy adults].

The contents of 15 trace elements in the sera of 30 liver cancer patients and 30 healthy adults were assayed by ICP-AES method. The data obtained were analysed by routine statistical tests, multi-variate discrimination analysis, multi-variate stepwise regression analysis and non-linear mapping algorithm. The results showed that the contents of copper, vanadium, cadmium, stannum, cobalt, nickel in liver cancer patients were significantly higher than those in healthy adults. The serum trace element spectrum of liver cancer patients was different from that of healthy adults. Hence, the liver cancer patients could be differentiated from healthy adults by serum trace element spectrum.

The effect of tin chloride on the structure and function of DNA in human white blood cells.

Tin compounds are being used increasingly in the home, in industry and in medicine. There have been relatively few studies on the long term biological effects of this metal, although acute effects have been documented. In this report we describe experiments which show that tin(II), as stannous chloride, is readily taken up by human white blood cells (WBC) and can cause damage to DNA. Damage was detected in WBC after exposure to 10-50 microM tin(II) for 30 min at either 0 degree or 37 degrees C. The amount of damage observed was more extensive than that produced by exposure of cells to equimolar amounts of chromium(VI), a known carcinogen and DNA damaging agent. Additional indication of cellular damage is that exposure of human lymphocytes or mouse splenocytes to tin(II) interfered with their ability to be stimulated by the polyvalent mitogen concanavalin A (Con A). By contrast, tin(IV) was not taken up by cells, did not cause DNA damage nor did it inhibit stimulation of DNA synthesis in cells that were exposed to Con A.