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Results for “Organotin Compounds”

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At least 19 recordsLinked to original sources

PubMed1984

Inhibition of neutrophil chemotaxis by organotin compounds.

Organotin compounds such as Bu2SnCl2, Bu3SnCl and Ph3SnCl suppressed significantly not only chemotactic response of neutrophils to stimulation by the chemoattractant fMet-Leu-Phe but also phospholipase activity in situ as measured by the release of [1-14C] arachidonic acid previously incorporated into phospholipids. Moreover, these suppressions were dose dependent and a parallelism was found between dose-dependent inhibition of chemotaxis and that of arachidonate release. These results suggest that the chemotactic response is controlled by the activation of phospholipase activity in neutrophils, and that the inhibitory effects of these organotin compounds on chemotactic response reflect the blockage of phospholipase activation system regulated by phosphorylation of lipomodulin.

Animals↗

PubMed1994

[Studies on the antitumor activity of organotin compounds].

Organotin compounds were found to obviously inhibit the activity of phospholipid/Ca(2+)-dependent protein kinase (PKC) in rat brain tissue and the proliferation of tumor cell lines in vitro. The results showed that a correlation exists between the effects on PKC and anti-proliferative and antitumor activities. The structure-activity relationship was shown to be as follows: (1) R, the organic group determines the biological activity; (2) electronegativity of the halogen can affect the activity. The organotin compounds inhibit tumor cells by its [SnR2]2+, and inhibit G1-->S phases of HL-60 cell cycle. The IC50 of [SnPh2F2], [SnPh2(CysOS)].H2O and [SnPh2Cl2.phen(CH3)2] are respectively 25, 15 and 20 mumol.L-1 on PKC, 0.5, 4.0 and 0.3 mumol.L-1 on HL-60 cells, 2.7, 9 and 1.5 mumol.L-1 on BEL-7402 cells, 2.2, 15 and 5.0 mumol.L-1 on KB cells. But no induction of differentiation of leukemic cell lines HL-60 and K562 was observed.

Animals↗

PubMed1996

Ecotoxicology of organotin compounds.

Organotin compounds are ubiquitous contaminants in the environment. The high biological activity of some compounds toward aquatic organisms lead to deleterious impacts in aquatic ecosystems. Here, the aquatic ecotoxicology of organotins is reviewed based on a multidisciplinary approach involving environmental chemical, toxicological, and ecological aspects. Basic results were obtained both with field and laboratory studies, and some of the most important recent results and conclusions are critically reviewed. The contamination of and fate in aquatic systems is reported and linked with effects at different levels of biological organization. Major emphasis is placed on the development of a concept of ecotoxicology that encompasses not only effect assessment alone, but also integrates environmental chemistry with aquatic toxicology. Thereby, the influence of speciation for bioavailability, basic modes of toxic action, and aquatic toxicity are discussed. This case study on organotins allows to a certain extent generalizations to ecotoxicology in general.

Animals↗

PubMed2001

Inhibition of cell proliferation and antitumor activity of a novel organotin compound.

Organotin compounds showed more antineoplastic effect against P388 leukemia in mice than any other class of compounds. However, they have not received as much attention as the platinum compounds. The present compound, Et2SnCl2.L [L = N-(2-pyridylmethylene)-4-toluidine] (OTC), showed an Sn-N bond length of 2.46 A which, because it is bigger than 2.39 A, is expected to achieve better formation of tin-DNA complexes. We previously reported on the synthesis and biological activity of this compound and on its ability to cause a delay in cell proliferation and sister chromatid exchanges in mouse bone marrow cells. In this study, we carried out further investigations on the antiproliferative and antitumor activity of OTC in relation to the cellular glutathione (GSH) level, which plays an important role in the cellular defense mechanism. OTC induced significant delay in the cell cycle in mouse bone marrow cells and, when the GSH level was low, the extent of the delay was reduced. The antitumor activity was determined in accordance with the US National Cancer Institute (NCI) standard protocol for primary screening in Dalton's lymphoma (DL) that was maintained by serial intraperitoneal transplantation. The T/C (treated/control) value was 146% when organotin was treated after transplantation; this improved significantly when buthionine sulfoximine (BSO), a GSH-depleting agent, was added 24 hours before the tin treatment. Our data suggest that the present tin compound has antiproliferative ability and can increase the survival of mice bearing DL. The endogenous GSH level influences the effect of the tin compound.

Animals↗

PubMed2006

Molecular targets of organotin compounds in endocrine disruption: do organotin compounds function as aromatase inhibitors in mammals?

Tributyltin (TBT) and triphenyltin (TPT) cause masculinization in female mollusks. These compounds may act as potential competitive inhibitors of aromatase, which converts androgens to estrogens, although effective concentrations are high. TBT and TPT may, therefore, increase the levels of unconverted androgens in invertebrates and vertebrates. However, at concentrations effective for aromatase inhibition, they are generally toxic to mammalian cells. These compounds markedly enhance aromatase activity and human chorionic gonadotropin (hCG) production, along with their mRNA expression, at very low concentrations in human choriocarcinoma cells. In ovarian granulosa cells, these compounds suppress aromatase gene expression at the same low concentrations. Therefore, it is suspected that, in mammals, these organotin compounds affect target molecules that regulate the gene expressions of aromatase and hCG, rather than functioning as aromatase inhibitors. Recently, it has been demonstrated that TBT and TPT directly bind to the retinoid X receptor (RXR) and the peroxisome proliferator-activated receptor (PPAR) gamma with high affinity and function as transcriptional activators. These compounds promoted adipocyte differentiation, which is triggered by the PPAR gamma/RXR signaling pathway. They may, therefore, exert their toxic effects through the activation of these pathways in mammals. Here, we review the potential endocrine disruption of organotin compounds via these nuclear receptors in mammals.

Animals↗

PubMed2004

Organotin compounds: toxicokinetic aspects.

Organotin compounds have a broad range of applications. While dialkyltin compounds are used primarily as stabilizers for plastics, trisubstituted organotins are mainly used as biocides e.g., as an active ingredient of marine antifouling paints for boats and ships. Since a number of organotin compounds have been demonstrated to be toxic, there is increasing concern that their widespread use may cause adverse effects within environmental and biological systems. Besides carcinogenic and neurotoxic effects, as well as effects on the reproductive system, the most obvious mammalian effects of both various di- and trisubstituted organotins were found on the immune system. Exposure of humans to organotin compounds can take place through consumption of contaminated fish and seafood. In human liver samples, mainly dibutyltin, the metabolite of tributyltin, could be detected indicating that organotin compounds are bioavailable after dietary exposure. The objective of this short review is to present various toxicokinetic aspects of organotin compounds in more detail. While several studies using in vitro systems investigated their metabolism especially by the monooxygenase system, various aspects of absorption, distribution, metabolism, and excretion (ADME) pathways of different organotin compounds were described by data obtained from several studies with laboratory animals. However, most of these studies were not conducted as full ADME studies but dealt only with some of these aspects. Therefore, for definitive conclusions in some cases, additional information is requested. By reviewing and updating the current literature consideration was given preferentially to those organotin compounds which have relevance with respect to human exposure and/or toxicological effects.

Animals↗

PubMedDate not supplied

[Suppression of Penicillium purpurogenum growth by organotin compounds].

We studied the effect of organotin compounds and their mixtures with N-cetylpyridinium chloride on the accumulation of biomass by Penicillium purpurogenum. Ditributylstannylic ester of fumaric acid at a concentration of 0.005 micrograms/ml was shown to inhibit the accumulation of biomass. If an organotin compound was used in combination with N-cetylpyridinium chloride, the fungicide effect was greater at a lower dose of the organotin compound in the mixture. Organotin compounds and their mixtures with N-cetylpyridinium chloride suppress protein biosynthesis in the fungal mycelium, increasing protein content in the cultural broth. The mechanism of action of organotin compounds on the growth of P. purpurogenum is discussed.

Cetylpyridinium↗

PubMed1999

Organotin compounds and their interactions with microorganisms.

Organotin compounds are ubiquitous in the environment. The general order of toxicity to microorganisms increases with the number and chain length of organic groups bonded to the tin atom. Tetraorganotins and inorganic tin have little toxicity. Because of their lipophilicity, organotins are regarded as membrane active. There is evidence that the site of action of organotins may be both at the cytoplasmic membrane and intracellular level. Consequently, it is not known whether cell surface adsorption or accumulation within the cell, or both is a prerequisite for toxicity. Biosorption studies on a fungus, cyanobacteria, and microalgae indicates that cell surface binding alone occurred in these organisms, while studies on the effects of TBT (tributyltin) on certain microbial enzymes indicated that in some bacteria TBT can interact with cytosolic enzymes. Microorganism-organotin interactions are influenced by environmental conditions. In aquatic systems, both pH and salinity can determine organotin speciation and therefore reactivity. These environmental factors may also alter selectivity for resistant microorganisms in polluted systems. Tin-resistant microorganisms have been identified, and resistance can be either plasmid or chromosomally mediated. In one TBT-resistant organism, an Altermonas sp., an efflux system was suggested as the resistance mechanism. Biotransformation of organotin compounds by debutylation or methylation has been observed. These reactions may influence the toxicity, mobility, and environmental fate of organotin compounds.

Bacteria↗

PubMed2003

Specific detection of organotin compounds with a recombinant luminescent bacteria.

Organotin compounds are widely used as biocides in marine and terrestrial environments. Several currently used techniques allow either the measurement of the chemicals or their effects on living organisms. Our current research focuses on the development of a complementary method based on a bacterial bioluminescence-based bioassay for the specific detection of organotin compounds. The performance of the bioassay was assessed. The Escherichia coli bacterial strain used in this study is specific for TBT and DBT (with Cl, Br or I as the halogen group) with the central tin atom important for light production. The assay is conducted after overnight culture of the bacterial strain, followed by 60 min of contact time with the organotin compound for significant light production. The detection limits were found to be 0.08 microM for TBT (26 microgl(-1)) and 0.0001 microM for DBT (0.03 microgl(-1)) with a linear range of one logarithm. The repeatability of the bioassay is 8% and the reproducibility for TBT and DBT was approximately 14%. Lyophilization of the strains did not significantly modify the detection limit as well as the range of detection. Applications of the bioassay to environmental samples are discussed.

Biological Assay↗

PubMed1980

Prolonged induction of hepatic haem oxygenase and decreases in cytochrome P-450 content by organotin compounds.

The administration of organotin compounds to rats in single doses causes a significant and prolonged induction of haem oxygenase and a sustained decrease in haemoprotein content in the liver. The extent of induction of hepatic haem oxygenase varied between 3 and 5-fold at 72h after a single injection of water-insoluble organotins of differing structure. The alterations in haem metabolism produced by tricyclohexyltin hydroxide were studied in detail. The effects were dose-dependent, with doses as low as 3.75 mg/kg body wt. resulting in significant induction of haem oxygenase and a decrease in cytochrome P-450 and cytochrome b5 contents at 72h in the liver. The effects with time of a single dose of tricyclohexyltin on various parameters of liver haem metabolism were also examined. The organotin produced a substantial and very prolonged induction of haem oxygenase accompanied by a steady decline in cytochrome P-450 content for periods up to 8 days. The long duration of action of these organotins with respect to induction of haem oxygenase and depletion of cellular haemoprotein content provides a highly sensitive metabolic system with which to define further the toxic potential of organometals as well as to study the adaptive responses in liver to long-term perturbations of haem metabolism by foreign chemicals.

Animals↗

PubMed2001

Organotin compounds alter the physical organization of phosphatidylcholine membranes.

Organotin compounds have a broad range of biological activities and are ubiquitous contaminants in the environment. Their toxicity mainly lies in their action on the membrane. In this contribution we study the interaction of tributyltin and triphenyltin with model membranes composed of phosphatidylcholines of different acyl chain lengths using differential scanning calorimetry, (31)P-nuclear magnetic resonance, X-ray diffraction and infrared spectroscopy. Organotin compounds broaden the main gel to liquid-crystalline phase transition, shift the transition temperature to lower values and induce the appearance of a new peak below the main transition peak. These effects are more pronounced in the case of tributyltin and are quantitatively larger as the phosphatidylcholine acyl chain length decreases. Both tributyltin and triphenyltin increase the enthalpy change of the transition in all the phosphatidylcholine systems studied except in dilauroylphosphatidylcholine. Organotin compounds do not affect the macroscopic bilayer organization of the phospholipid but do affect the degree of hydration of its carbonyl moiety. The above evidence supports the idea that organotin compounds are located in the upper part of the phospholipid palisade near the lipid/water interface.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed1982

[Recent progress in the study of analytical methods, toxicity, metabolism and health effects of organotin compounds].

Over the years, a variety of uses has been found of organic tin compounds as fungicides, as stabilizers in plastics and for other industrial uses. The purpose of this article is to summarize and review the results so far obtained as to the analytical method for organotins in biological samples, the toxicity, metabolism, and biochemical and health effects of organotin compounds. 1) Many methods have been developed for analysis of organotin compounds by spectrophotometry, polarography, gas- or liquid-chromatography, etc. These methods, however, are mainly for analysis of organotins in standard solutions or in water, and are not suitable for organotin compounds in biological samples. Recently, we have developed several methods for analysis of various kinds of organotin compounds in biological samples. These methods are able simultaneously to separate and determine trace amounts (at nanogram order) of organotin compounds and their metabolites in the same biological samples. 2) Acute toxicity of organotin compounds which appeared on the literature are summarized. Trialkyl and triaryl compounds seem to be more toxic than the tetra-, di-, or mono-compounds of the same chain length. With an increase in the number of C atoms the toxicity of alkyl compounds decreases. Aryltin compounds are less toxic than alkyltin compounds. 3) Intestinal absorption sites for tetra-alkyltins are jejunum and duodenum, and those for trialkyltins are ileum and jejunum. A considerable amount of orally administered tetra- and trialkyltins of low molecular weights are absorbed, but only very little of the other organotin compounds seems to be absorbed from the gastrointestinal tract. Absorbed organotin compounds rapidly undergo dealkylation by the microsomal mono-oxygenase system dependent on cytochrome P-450 in the liver, brain or other organs, and the compounds and their metabolites distribute to the whole body, ultimately being excreted into urine, bile and faeces. The biological half life of organotin compounds in mammals is usually short, a half of the amount of tributyl- and triphenyl-tins deposited in the body disappearing in several days. A part of organotin compounds excreted into bile is demonstrated to have been absorbed from the intestine and to circulate in the body via enterohepatic circulation. 4) Specific effects of organotin compounds on the biological systems and health include disturbance of the structure and function of the central nervous system (interstitial edema of white matter), inhibited oxidative phosphorylation in mitochondria of cells, atrophy of the thymus and thymus dependent lymphoid tissues resulting in the dysfunction of T cells for immunity, inhibited enzyme activity, lesions in the liver and bile ducts etc., although some specificity is observed among species of animals and organotin compounds. Recently we found that a single oral administration of triphenyltin fluoride to rabbits induces transient diabetes and diabetic lipemia by inhibiting insulin secretion from morphologically normal pancreatic B-cells...

Animals↗

PubMed1993

Studies on the mechanism of oxidative phosphorylation. ATP synthesis by submitochondrial particles inhibited at F0 by venturicidin and organotin compounds.

Oligomycin,N,N'-dicyclohexylcarbodiimide (DCCD), venturicidin, and tetracoordinate organotin compounds (R3SnX) are potent inhibitors of the mitochondrial ATP synthase complex, all acting on the membrane sector, F0. Oligomycin and DCCD inhibit proton translocation through F0 and energy transfer between F0 and the catalytic sector, F1, of the ATP synthase complex. Our results have shown that venturicidin and organotin compounds (tributyltin and triphenyltin chloride were used) greatly attenuate these processes, but do not cause complete inhibition. As a result, bovine submitochondrial particles (SMP) treated with venturicidin or tributyltin chloride were shown to be capable of ATP hydrolysis and synthesis, albeit at very slow rates. We had shown previously that in ATP synthesis Vmax and apparent Km for ADP and Pi increase or decrease, respectively, as the steady-state membrane potential is elevated or lowered (Matsuno-Yagi, A., and Hatefi, Y. (1986) J. Biol. Chem. 261, 14031-14038). These changes occurred at constant Vmax/Km, suggesting that the apparent Km changes were due mainly to kcat changes. Results presented here show that, in respiring SMP treated with venturicidin or organotin compounds, the membrane potential is near the static-head level, but the slow rate of ATP synthesis takes place with a low KmADP value of 2-3 microM. In agreement with our previous conclusions, these results indicate that it is not the membrane potential per se that affects KmADP during ATP synthesis, but rather it is the rate of energy transfer from F0 to F1 that influences both Vmax and KmADP. Further conclusions from the above studies have been discussed in relation to the possible mechanism of energy transfer between F0 and F1 and the manner in which venturicidin and organotin compounds might attenuate this process.

Adenosine Triphosphate↗

PubMed1998

Distribution pattern of organotin compounds at different trophic levels of aquatic ecosystems.

Organotin compounds including methyl- and butyltin species were determined in selected aquatic specimens (fish muscles, fish liver, mussels, algae) as well as in sediment and water from the mud flats of the German North Sea and the River Elbe. The concentration of tributyltin (TBT) ranged between 27-202 ng/g (fresh mass) in fish muscles, 54-223 ng/g (fresh mass) in fish liver, 10-25 ng/g (fresh mass) in common mussels and 42-97 ng/g (fresh mass) in bladderwrack. The concentration of total organotin compounds (mono-, di-, and trimethyltin + mono-, di-, and tributyltin) in water samples along the River Elbe up to the Elbe estuary ranged between 30-96 ng/l. Retrospective investigation of butylin compounds in mussel samples from the North Sea was performed by the analysis of cryogenically stored samples from 1985. A comparison of the results with that in muscles from 1993 shows that the total tin content and the TBT content decreased from 1985-1993 by a factor of 3.5 and 6.5, respectively. In addition estimated bioconcentration factors (BCF) for organotin compounds in samples from different trophic levels are presented.

Animals↗

PubMed1993

Inhibition of mouse spleen cell activity by organotin compounds: effect of attachment of a maltose residue to the organotin group.

Studies are reported on the inhibition of DNA synthesis and the lowering of cell viability caused by bis(tributyltin) oxide in mouse spleen cells cultured in the presence and absence of the B-lymphocyte mitogen, bacterial lipopolysaccharide. When a maltose residue is introduced into the organotin compound these toxic effects are increased. It is suggested that the maltose residue facilitates entry of the organotin compound into the cells.

Animals↗

PubMed1991

Laser-excited atomic fluorescence in a flame as a high-sensitivity detector for organomanganese and organotin compounds following separation by high-performance liquid chromatography.

The coupling of a high-performance liquid chromatograph with a sensitive and selective laser-excited atomic fluorescence spectrometry (LEAFS) detector is described. In connection with this, a study of the signal and noise characteristics of instrumentation for dispersive, nondispersive, and front surface LEAFS is reported together with a comparison of the sensitivity and selectivity achieved with high-performance liquid chromatography (HPLC)-flame LEAFS, HPLC-ultraviolet (UV), and HPLC-continuum source excited flame atomic fluorescence spectrometry (AFC) instrumentation. The HPLC-flame LEAFS instrumentation was applied to an investigation of the Mn species responsible for (methylcyclopentadienyl)manganese tricarbonyl (MMT) toxicity in rats. The detection limits for various organomanganese species by HPLC-flame LEAFS ranged from 8 to 22 pg of manganese. Recovery of these compounds from rat urine varied between 80% and 100%, with a reproducibility of between 4% and 8% relative standard deviation. Preliminary data for the HPLC-flame LEAFS determination of toxic alkyltin compounds are reported.

Chromatography, High Pressure Liquid↗

PubMed1979

Inhibition of the enzymatic activity of ligandin by organogermanium, organolead or organotin compounds and the biliary excretion of sulfobromophthalein by the rat.

Ligandin binds several classes of compounds, has glutathione-S-transferase activity and is postulated to function in the intracellular transport of substances which bind to it and/or are substrates for its enzymatic activity. The effects of a group of organometals reported to inhibit the enzymatic activity of ligandin on the biliary excretion of sulfobromophthalein have been investigated to determine what role the enzymatic activity of ligandin has with respect to the biliary excretion of the dye. Triethyllead reduced the rate of dye excretion into the bile without affecting blood pressure, blood or liver sulfhydryl compounds or the volume of bile flow. The organometal had no effect on the initial rate of plasma dye clearance. Inhibited biliary sulfobromophthalein excretion by triethylead-treated rats correlated with relative increases in liver and bile unconjugated dye, decreases in liver and bile conjugated dye and reduced glutathione-S-aryltransferase activity in supernatant fractions isolated from the liver. The results clearly demonstrated that the tested organometals can inhibit the enzymatic activity of ligandin in vivo and suggested that, if ligandin has a role in the translocation of the dye from the blood to the liver, the enzymatic activity of the protein may not be involved.

Animals↗

PubMed2004

Inhibitory effect of organotin compounds on rat neuronal nitric oxide synthase through interaction with calmodulin.

Organotin compounds, triphenyltin (TPT), tributyltin, dibutyltin, and monobutyltin (MBT), showed potent inhibitory effects on both L-arginine oxidation to nitric oxide and L-citrulline, and cytochrome c reduction catalyzed by recombinant rat neuronal nitric oxide synthase (nNOS). The two inhibitory effects were almost parallel. MBT and TPT showed the highest inhibitory effects, followed by tributyltin and dibutyltin; TPT and MBT showed inhibition constant (IC(50)) values of around 10microM. Cytochrome c reduction activity was markedly decreased by removal of calmodulin (CaM) from the complete mixture, and the decrease was similar to the extent of inhibition by TPT and MBT. The inhibitory effect of MBT on the cytochrome c reducing activity was rapidly attenuated upon dilution of the inhibitor, and addition of a high concentration of CaM reactivated the cytochrome c reduction activity inhibited by MBT. However, other cofactors such as FAD, FMN or tetrahydrobiopterin had no such ability. The inhibitory effect of organotin compounds (100microM) on L-arginine oxidation of nNOS almost vanished when the amount of CaM was sufficiently increased (150-300microM). It was confirmed by CaM-agarose column chromatography that the dissociation of nNOS-CaM complex was induced by organotin compounds. These results indicate that organotin compounds disturb the interaction between CaM and nNOS, thereby inhibiting electron transfer from the reductase domain to cytochrome c and the oxygenase domain.

Amino Acid Oxidoreductases↗