Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Trialkyltin Compounds”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources
PubMedDate not supplied

The toxicity and neuropathology of dimethylethyltin and methyldiethyltin in rats.

Triethyltin causes an increase in brain water with vacuolation of myelin sheaths, whereas trimethyltin is selectively damaging to neurons, especially of the hippocampal formations, causing chromatolysis, accumulation of cytoplasmic dense bodies and often cell death. The effects on rats of the analogues, dimethylethyltin and methyldiethyltin (oral LD50 14 mg/kg and 7.5-10.0 mg/kg respectively) are now reported. The dimethylethyl compound produces functional changes resembling those caused by trimethyltin, while the methyldiethyl compound causes responses similar to those produced by triethyltin. Structurally, however, the dimethylethyl compound, while producing marked nerve cell changes of the trimethyltin type also causes moderate vacuolation of myelin sheaths. By contrast, methyldiethyltin causes marked vacuolation of myelin sheaths of the triethyltin type and relatively minor neuronal changes of the trimethyltin type. These findings are discussed in terms of the structure-activity relationships of trialkyltin compounds.

Animals↗
PubMed1983

Direct in vitro effects of bis(tri-n-butyltin)oxide on hepatic cytochrome P-450.

Bis(tri-n-butyltin)oxide, an agriculturally important biocidal agent, when added in vitro to liver microsomes containing the phenobarbital-induced form of cytochrome P-450, produced a typical type I binding spectrum (an absorption maximum at 390 nm; an absorption minimum at 420 nm). Studies with microsomal preparations containing cytochrome P-448, induced by 3-methylcholanthrene or beta-naphthoflavone, revealed that this hemeprotein was more susceptible to direct degradation by bis(tri-n-butyltin)oxide than was the uninduced or phenobarbital-induced forms of cytochrome P-450. The disappearance of spectrally detectable cytochrome P-450 was accompanied by an increase in cytochrome P-420. The formation of cytochrome P-420 was both time and temperature dependent, and it also occurred to a greater extent in microsomal preparations containing cytochrome P-448 than in microsomes containing the phenobarbital-induced form of cytochrome P-450. In all cases, the decreases in spectrally detectable cytochrome P-450 produced by the organotin were not accompanied by decreases in microsomal heme or cytochrome b5 content. The findings provide evidence for the direct interaction followed by conversion of cytochrome P-450 to cytochrome P-420 produced by a trialkyltin compound in vitro, and indicate that different susceptibilities to degradation exist within the various subspecies of this hemeprotein.

Animals↗
PubMed1989

Flow cytometric comparison of the effects of trialkyltins on the murine erythroleukemic cell.

Cellular effects of exposure to tributyltin (TBT), triethyltin (TET), or trimethyltin (TMT) were investigated by flow cytometry employing the murine erythroleukemic cell (MELC) as a model cellular system. Cell viability was investigated by the carboxyfluorescein diacetate (CFDA) uptake/propidium iodide (PI) exclusion method: above a critical concentration (exposure for 4 h), which was specific for each of the trialkyltin compounds, the cell becomes permeable to PI, indicating loss of viability. Cellular CF fluorescence (derived from intracellular hydrolysis of CFDA) increased as a function of alkyltin concentration below the critical concentration and decreased as viability decreased above the critical concentration. Relative membrane potential, monitored with a cyanine dye (DiOC6), correlated with viability (PI exclusion), remaining essentially unaltered below the critical concentration and decreasing above it. At/above 1 microM TBT, 5 microM TET, or 100 microM TMT, the cell cycle was blocked in the G2/M phase. The 90 degrees light scatter (a measure of refractive index), axial light loss (a measure of volume), and fluorescein isothiocyanate (FITC) fluorescence (a measure of protein content) of nuclei isolated from trialkyltin-treated MELC by detergent treatment, increased as a function of organotin dose. Fluorescence and interference microscopy revealed increased quantities of residual cytoplasmic tags adherent to the nuclei as a function of organotin dose, apparently resulting from increased cytoplasmic resistance to detergent-mediated solubilization. The effects of the trialkyltins correlated with their lipophilicity (octanol/water coefficient). These data support the hypothesis that fixation (protein denaturation, cross-linking, etc.) is an important mode of organotin cytotoxicity.

Animals↗
PubMedDate not supplied

Developmental and behavioral toxicity following acute postnatal exposure of rat pups to trimethyltin.

The purpose of this study was to extend our investigations on the developmental neurotoxicity of trialkyltin compounds. On postnatal day 5 (PND 5), rat pups received a single intraperitoneal injection of either 0 (saline), 4, 5 or 6 mg/kg trimethyltin hydroxide (TMT) calculated as the base. The size of the milk bands was decreased in 6 mg/kg TMT pups 48-96 hr after dosing, while in 5 mg/kg TMT pups, milk bands were reduced 96 hr after dosing only. Dosages of 5 and 6 mg/kg TMT reduced growth and impaired performance in rope descent during the preweaning period. As adults, motor activity in figure-eight mazes was increased for 6 mg/kg TMT animals. The startle response to an acoustic stimulus (a 13 kHz, 120 dB tone) was also affected by TMT when measured both during ontogeny and in adulthood. During development, on days 10-21, both 5 and 6 mg/kg TMT reduced the number of responses during 30-trial sessions for both males and females. Amplitudes were decreased for the 5 and 6 mg/kg dose on days 12-13, and for all dosages on days 18-19 and 20-21. Startle amplitude of adults was decreased at all dosages for males but not for females. These behavioral changes were accompanied by decreases in adult brain weight for both sexes. Whole brain weight and weight of the olfactory bulbs were decreased following all dosages of TMT, while hippocampal weight was decreased following both 5 and 6 mg/kg TMT. These results indicate that acute postnatal exposure to TMT produces long-term effects on the nervous system and behavior.

Animals↗
PubMed1980

Effects of trialkyllead compounds on growth, respiration and ion transport in Escherichia coli K12.

Triethyllead and tripropyllead cations affected growth, energy metabolism and ion transport in Escherichia coli K12. The tripropyllead compound was more liposoluble than the triethyl analogue and was also more effective in inhibiting cell growth and the oxygen uptake of both intact cells and membrane particles. Triethyllead acetate (5 microM) inhibited growth on non-fermentable carbon sources, such as glycerol and succinate, more markedly than on glucose. At higher concentrations, triethyllead caused significant inhibition of respiration rates of intact cells; the concentration giving 50% inhibition was 60 microM for glycerol-grown cells and 150 microM for glucose-grown cells. Oxidation of succinate by membrane particles was less sensitive to inhibition by the tripropyl- or triethyllead compounds than were the oxidations of DL-lactate or NADH. Triethyllead acetate [1.9 mumol (mg membrane protein)-1] inhibited the reduction by NADH of cytochromes; evidence for more than one site of inhibition in the respiratory chain was obtained. Membrane-bound ATPase activity was strongly inhibited by triethyllead acetate in the absence or presence of Cl-. The concentration of inhibitor giving 50% inhibition [0.02 mumol (mg membrane protein)-1] was about two orders of magnitude lower than that required for 50% inhibition of substrate oxidation rates in membranes. Triethyllead acetate (1 microM) induced swelling of spheroplasts in iso-osmotic solutions of either NH4Cl or NH4Br, presumably as a result of the mediation by the organolead compound of Cl-/OH- and Br-/OH- antiports across the cytoplasmic membrane. Similar exchanges of OH- for F-, NO3- or SO4(2)- or the uniport of H+ could not be demonstrated. Comparisons are drawn between the effects of trialkyllead compounds and those of the more widely studied trialkyltin compounds.

Adenosine Triphosphatases↗
PubMed2003

Dealkylation of organotin compounds by biological dithiols: toward the chemistry of organotin toxicity.

In this Communication, we report evidence for the dealkylation of trialkyltin compounds by a short linear peptide extracted from a small membrane protein (stannin) involved in cellular apoptosis and containing a CXC motif. We show that (a) organotin binding induces the formation of a beta-turn in the linear peptide, (b) both cysteines are necessary for the dealkylation reaction, and (c) stable 1:1 complexes are formed between the peptide and diorganotins that can be observed by ESI-MS. Organotin degradation by biological dithiols may be responsible for both the delayed activity of these toxins in humans and the organotin resistance mechanisms in bacteria.

Alkylation↗
PubMed1972

Biochemical effects of the hypoglycaemic compound diphenyleneiodonnium. Catalysis of anion-hydroxyl ion exchange across the inner membrane of rat liver mitochondria and effects on oxygen uptake.

1. The hypoglycaemic compound diphenyleneiodonium causes rapid and extensive swelling of rat liver mitochondria suspended in 150mm-NH(4)Cl, and in 150mm-KCl in the presence of 2,4-dinitrophenol and valinomycin. This indicates that diphenyleneiodonium catalyses a compulsory exchange of OH(-) for Cl(-) across the mitochondrial inner membrane. Br(-) and SCN(-) were the only other anions found whose exchange for OH(-) is catalysed by diphenyleneiodonium. 2. Diphenyleneiodonium inhibited state 3 respiration of mitochondria and slightly stimulated state 4 respiration with succinate or glutamate as substrate in a standard Cl(-)-containing medium. 3. Diphenyleneiodonium did not inhibit state 3 respiration significantly in two Cl(-)-free media (based on glycerol 2-phosphate or sucrose) but caused some stimulation of state 4. 4. In Cl(-)-containing medium diphenyleneiodonium only slightly inhibited the 2,4-dinitrophenol-stimulated adenosine triphosphatase and it had little effect in the absence of Cl(-). 5. The inhibition of respiration in the presence of Cl(-) is dependent on the Cl(-)-OH(-) exchange. 2,4-Dichlorodiphenyleneiodonium is ten times as active as diphenyleneiodonium both in causing swelling of mitochondria suspended in 150mm-NH(4)Cl and in inhibiting state 3 respiration in Cl(-)-containing medium. Indirect evidence suggests that the Cl(-)-OH(-) exchange impairs the rate of uptake of substrate anions. 6. It is proposed that stimulation of state 4 respiration in the absence of Cl(-) depends, at least in part, on an electrogenic uptake of diphenyleneiodonium cations. 7. Tripropyl-lead acetate, methylmercuric iodide and nine substituted diphenyleneiodonium derivatives also catalyse Cl(-)-OH(-) exchange across the mitochondrial membrane. 8. Diphenyleneiodonium is compared with the trialkyltin compounds, which are also known to mediate Cl(-)-OH(-) exchange and which have in addition strong oligomycin-like effects on respiration. It is concluded that diphenyleneiodonium is specific for catalysing anion-OH(-) exchange and will be a useful reagent for investigating membrane-dependent systems.

Acetates↗
PubMed1997

Capillary electrophoresis of organotin compounds with indirect UV detection.

A capillary electrophoresis (CE)-indirect UV absorbance detection method for organotin compounds is described. The five triorganotin cations, viz., trimethyltin (TMT), triethyltin (TET), tripropyltin (TPT), tributyltin (TBT) and triphenyltin (TPhT), were efficiently separated by CE in 10 min with a 5 mM acetate buffer (pH 4.5) containing 3 mM 4-aminopyridine (4-AP). 4-AP also functioned as a UV-absorbing coion for the indirect detection of these UV-transparent organotin species. Simultaneous separation of di- and triorganotins was achieved with the addition of alpha-cyclodextrin (alpha-CD) as a modifier in the electrophoresis buffer. Linearity (r > or = 0.995) of about two orders of magnitude was generally obtained. The concentration limits of detection for the organotin compounds studied were between 2 and 20 microM (as tin). The relative standard deviation (RSD) values were in the range 1.3-7.1%. The applicability of the method for the analysis of marine sediment was examined.

Calibration↗
PubMed1986

Inhibition of tributyltin mediated hemolysis by mercapto compounds.

Hydrophobic tributyltin (TBT) compounds at concentrations greater than 10 microM caused hemolysis of human erythrocytes and formed structures in plasma membranes. The mercapto compounds, beta-mercaptoethanol (beta MER), 2,3-dimercaptopropanol (BAL), 2,3-dimercapto-1-propane sulfonate (DMPS), DL-dithiothreitol (DTT), and meso-2,3-dimercaptosuccinic acid (DMSA) were examined for their ability to inhibit TBT mediated hemolysis. The relative order of effectiveness for inhibition of TBT mediated hemolysis was BAL greater than DTT greater than DMSA greater than DMPS greater than beta MER. A four-fold excess of BAL over TBT prevented hemolysis for 4 hrs and addition of BAL 0.5 hr after TBT reduced the rate of hemolysis. The number of membrane associated TBT aggregates observed per cell profile decreased as the BAL concentration increased from 0 to 100 microM. However, the mean diameter of TBT aggregates nearly doubled in erythrocyte suspensions at 100 microM BAL. Reactions of dimercapto compounds with lipophilic TBT aggregates may depend on their relative lipid solubilities. Also, conversion of the weak Lewis acid, TBT, from a four to a five or six-coordinate tin adduct by the dimercapto Lewis bases used could also be a factor slowing hemolysis rates.

Erythrocytes↗
PubMed1999

Immunotoxicity of environmentally relevant concentrations of butyltins on human natural killer cells in vitro.

The widespread environmental contamination, bio-accumulation, and toxic effects of butyltins (BTs) in wildlife is well documented, but the role of BTs in debilitating human immune function mediated through natural killer (NK) lymphocytes (a primary immune defense against tumor and virally infected cells) has not been described. In this study, we assessed the effects of in vitro exposure to a range of concentrations (encompassing environmentally relevant concentrations) of MBT, DBT, and TBT on human natural killer lymphocytes obtained from adult male and female donors. TBT inhibited the tumor-killing capacity of NK cells when the NK cells were pretreated in vitro at 200 nM for as little as 1 h. Inhibition of NK cytotoxic function ranged from 40 to greater than 90%. The toxic potential of butyltins followed the order of TBT > DBT > MBT. Conjugation assays revealed that after a 24-h exposure to TBT, there was about a 50% decrease in NK cell binding to tumor cells, indicating alteration of the NK cell receptors for tumor cells. Analysis of whole-blood samples for BTs revealed the presence of detectable concentrations of MBT, DBT, and TBT in all of the donors, indicating possible exposure of NK cells to BTs in the blood. The results of this study provide evidence that butyltin compounds significantly inhibit NK cell function and possible NK cell-mediated immunotoxic potential in humans.

Adult↗
PubMed2002

Brief butyltin exposure induces irreversible inhibition of the cytotoxic function on human natural killer cells, in vitro.

Despite mounting evidence on butyltin (BT) contamination and related immunotoxic effects on wildlife, very little is known about BT-associated immunotoxic effects on humans, particularly the effects on human natural killer (NK) lymphocyte function. Our earlier studies demonstrated that in vitro exposure to environmentally relevant concentrations of BTs negatively affect human NK cells and that there are measurable levels of BTs in human blood. In this study we examined whether the inhibition of NK cell cytotoxic function induced by a brief exposure (1 h) to BTs is reversible when the cells are allowed to recover in BT-free media for up to 6 days. Standard methods were used in chemical preparation, blood sampling, NK cell isolation, and 51-Chromium release assay. The results revealed that exposure to 300 nM TBT for 1 h caused an approximately 65- decrease in NK cytotoxic function, whether the lymphocytes were given as long as a 6-day recovery period or no recovery period. There was no recovery (nor any further loss) of NK cytotoxic function following removal of the compound. Exposure to 5 microM DBT for 1 h showed a 41% decrease in cytotoxic function with 0-h recovery and an 83% decrease after a 24-h recovery period. Thus, not only is there no significant recovery of NK cytotoxic function when the lymphocytes are allowed to incubate in BT-free medium for up to 6 days but there is additional loss of cytotoxic function. The results indicated that short-term exposure to BTs causes persistent negative effects on NK cell ability to kill cancer cells.

Adenosine Triphosphate↗
PubMed2000

Activation of mitogen-activated protein kinases by tributyltin in CCRF-CEM cells: role of intracellular Ca(2+).

Effects of tributyltin chloride (TBT) and other organotin compounds on mitogen-activated protein kinases (MAPKs) were examined in CCRF-CEM human T lymphoblastoid cells. In response to the incubation with 0.25-2 microM TBT for 1 h, the levels of the phosphorylated form of extracellular signal-regulated protein kinase (ERK), c-Jun NH(2)-terminal kinase (JNK), and p38 MAPK increased in a dose-dependent manner. The phosphorylation was observed after 15 min and lasted for 4 h following exposure to 1 microM TBT, while the cell viability was not lowered significantly within 6 h. On the other hand, no clear changes were found in the total protein levels of ERK, JNK, and p38 MAPK. The in vitro activities of MAPKs also increased in response to TBT exposure. The potentials of MAPKs phosphorylation and of cellular damage were TBT > dibutyltin dichloride (DBT) > monobutyltin trichloride (MBT). When compared to other triorganotin compounds such as trimethyltin chloride (TMT), triphenyltin chloride (TPT), and triethyltin bromide (TET), TBT exposure induced the most marked phosphorylation of MAPKs. Chelation of intracellular Ca(2+) suppressed TBT-induced MAPKs phosphorylation almost completely, but removal of external Ca(2+) did not. The present results showed that tributyltin is a potent activator of ERK, JNK, and p38 MAPK pathways, and Ca(2+) mobilized from intracellular stores plays an important role for the phosphorylation of MAPKs in this human T cell line.

Apoptosis↗
PubMed2001

Butyltin exposure causes a rapid decrease in cyclic AMP levels in human lymphocytes.

Natural killer (NK) cells are a subset of lymphocytes that are capable of killing tumor cells, virally infected cells, and antibody-coated cells. Butyltins (BTs) are used in a variety of consumer products and industrial applications. Tributyltin (TBT) is found in dairy products, meat, and fish. Dibutyltin (DBT) is found in plastic products, beverages stored in PVC pipes during manufacturing, and poultry products. BTs appear to increase the risk of cancer and viral infections in exposed individuals. This increased risk may be due in part to the inhibitory effect of these compounds on the cytotoxic function of NK cells. A 24-h exposure of NK cells to 200 nM TBT or 1.5 microM DBT decreased the cytotoxic function of NK cells by greater than 90%. Higher concentrations of TBT and DBT decreased the cytotoxic function of NK cells (by greater than 90%) after only a 1-h exposure. A 24-h exposure to either TBT or DBT decreased intracellular ATP levels by about 30%. However, as much as a 1-h exposure to either 300 nM TBT or 10 microM DBT caused no significant decrease in ATP levels. Thus, a decrease in ATP levels is a longer-term consequence of BT exposure. Intracellular levels of cAMP are decreased by as much as 80% within 5 min of exposure to either TBT or DBT. This rapid decline in cAMP levels in NK cells may be a consequence of BT exposure that is related to the rapid decrease in the cytotoxic function of NK cells.

Adenosine Triphosphate↗
PubMed1985

Meso-2,3-dimercaptosuccinic acid increases the inhibition of glutathione S-transferase activity from rat liver cytosol supernatants by di-n-butyltin dichloride.

Di-n-butyltin dichloride (DBTC) and tricyclohexyltin chloride (TCHTC) inhibited the glutathione S-transferase activity of rat liver cytosolic supernatants towards 1-chloro-2,4-dinitrobenzene. Meso-2,3-dimercaptosuccinic acid increased inhibition of glutathione S-transferase by DBTC but lowered inhibition of the enzyme by TCHTC.

Animals↗
PubMed1994

Triphenyltin as inductor of mitochondrial membrane permeability transition.

The effect of triphenyltin on mitochondrial Ca2+ content was studied. It was found that this trialkyltin compound induces an increase in membrane permeability that leads to Ca2+ release, drop of the transmembrane potential, and efflux of matrix proteins. Interestingly, cyclosporin A was unable to inhibit triphenyltin-induced Ca2+ release. Based on these results it is proposed that the hyperpermeable state is produced by modification of 2.25 nmol of membrane thiol groups.

Animals↗
PubMed1990

Electrically silent anion transport through bilayer lipid membrane induced by tributyltin and triethyllead.

The method of the measurement of the nonelectrogenic fluxes of hydrogen (or hydroxyl) ions (JH) based on the local proton gradients formation in the unstirred layers near a bilayer lipid membrane (BLM) is applied for recording the nonelectrogenic anion/OH- exchange on BLM induced by tributyltin (TBT) and a novel carrier (Hager, A., Moser, I., & Berthold, W. 1987. Z. Naturforsch., 42C:1116-1120), triethyllead (TEL). This method has been used previously for measuring the cation fluxes through BLM. TBT and TEL are shown to be equally efficient in the induction of Cl-/OH- exchange. JH induced by TBT is constant at 4 less than pH less than 7. JH decreases at pH less than 4 and pH greater than 7. Both ionophores have a transport sequence: I- greater than Br- greater than Cl- greater than F-. The quantitative measurements reveal that TEL better discriminates these four anions than TBT. It is concluded that this method may prove helpful in a search and study of anion/OH(-)-exchangers isolated from natural membranes.

Anions↗