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PubMed1992

Molecular neurotoxicology of trimethyltin: identification of stannin, a novel protein expressed in trimethyltin-sensitive cells.

The molecular basis of selective vulnerability of specific neuronal populations to neurotoxicants remains a key focus in neurotoxicology. Trimethyltin (TMT) selectively damages neurons in rodent and human central nervous system after a single exposure. By coupling subtractive hybridization with molecular cloning techniques, we isolated a cDNA specifically localized in TMT-sensitive cells. This 2.9-kilobase cDNA encodes a putative 10-kDa peptide of 88 amino acids, termed "stannin." In immunocytochemical experiments, antisera raised against the amino terminus of stannin exhibited strong immunoreactivity in TMT-sensitive neurons in the hippocampus and entorhinal cortex, areas previously identified by in situ hybridization. Northern blot and in situ hybridization experiments detected a 3.0-kilobase stannin mRNA in brain, spleen, and kidney; expression occurred as early as embryonic day 15 in rat brain and thymus. In situ hybridization in human hippocampus demonstrated a stannin mRNA in pyramidal and dentate gyrus neurons. High stringency Southern blot analysis of genomic DNA identified stannin homologs in rabbit, Drosophila, and human. These findings indicate that stannin is present in TMT-sensitive cells and may play a role in the selective toxicity of organotin compounds.

Amino Acid Sequence↗
PubMed1986

Trimethyltin-induced alterations in brain amino acids, amines and amine metabolites: relationship to hyperammonemia.

An investigation of several neurochemical consequences of exposure of the rat to 3/4 of the estimated single injection LD50 quantity of trimethyltin chloride (TMT) indicated that a significant elevation in the levels of glutamine (Gln) and 5-hydroxyindole acetic acid (5-HIAA) occurred at post-dosing day 7 in each examined region of the brain; elevated Gln persisted in the hippocampus through day 14 and returned to control levels at day 28. At post-dosing day 7, levels of glutamate were decreased in the hippocampus, while levels of GABA were decreased in hippocampus and frontal cortex, but not in corpus striatum; hippocampal glutamate and GABA returned to control levels by post-dosing day 14. Decreased levels of taurine (Tau) occurred on day 7 in both hippocampus and frontal cortex; hippocampal Tau remained below control levels through post-dosing day 28. Levels of other amino acids and of amines and amine metabolites were not altered by TMT in the 7 to 28 day post-dosing interval. At day 7, TMT treatment did not alter brain regional activities of glutamine synthetase; however, plasma ammonia was elevated 100% above the control value. Alterations in several serum enzymes (esp., alkaline phosphatase and aspartate aminotransferase) revealed several other peripheral consequences of TMT exposure which persist through post-dosing day 28. The more prominent and wide-spread neurochemical alterations resulting from TMT exposure appear to reflect consequences of hyperammonemia resulting from a peripheral effect of the organotin compound.

Amino Acids↗
PubMedDate not supplied

In vitro studies on tin-dithiocarbamates.

Organotin compounds have been studied for their biological properties, whereas very little is known about the effects of tin-inorganic derivatives on biological systems. Owing to our interest in the dithiocarbamate moiety in relation to metal redistribution in the body and to its biological import, we performed in vitro cytotoxicity experiments on dithiocarbamates. Preliminary results obtained with five tin-dithiocarbamates, where DDTC is the diethyldithiocarbamate anion, indicate some very promising compounds.

Animals↗
PubMedDate not supplied

Assessment of chemicals using a battery of neurobehavioral tests: a comparative study.

Single-dose LD10S and LD50S were determined in male, Fischer-344 rats for acrylamide monomer, arsenic trioxide, chlordecone, lead acetate, methylmercury hydroxide, monosodium salicylate, tetraethyl tin, and triethyl lead chloride. Proportions of the single-dose LD10S were used in a subacute study to estimate the 28-day LD20S for each chemical. Proportions of the 28-day LD20S were used in a subchronic (105 days of dosing) study to determine the effectiveness of a battery of neurobehavioral tests for detecting and characterizing the neurotoxic effects of each chemical. The battery consisted of undifferentiated motor activity, forelimb and hindlimb grip strengths, rotation orientation, thermal sensitivity, startle responsiveness to acoustic and air-puff stimuli, and performance of a multisensory conditioned pole-climb avoidance response task; body weight and rectal temperature were also monitored. The battery of tests was administered on eight occasions, that is, before, at three-week intervals during dosing (PO or IP, five days each week for 15 weeks), and at three and six weeks after dosing. Normative data (controls from each experiment) indicated fair overall stability of the measures over the eight test sessions, but experiment-to-experiment variability in this regard was clearly evident. The inherent statistical sensitivity of the tests varied greatly as estimated by their coefficients of variation, which ranged from 1% (rectal temperature) to over 100% (rotation orientation). Intercorrelations among the various measures were low to moderate indicating relatively little redundancy. The various measures were differentially affected by the eight chemicals: body weight by all eight; rectal temperature by one; undifferentiated motor activity by three; forelimb grip strength by two; hindlimb grip strength by four; rotation orientation by one; thermal sensitivity by one; startle responsiveness by three; and CAR performance by five. A profile analysis using the slopes of the dose-response functions after 15 weeks of dosing indicated clearly different patterns of effect among the eight chemicals. A composite score derived from a multidimensional analysis of the data suggested that the eight chemicals could be ranked from most to least neurotoxic as defined by these tests as acrylamide greater than methylmercury greater than chlordecone greater than tetraethyl tin greater than triethyl lead greater than lead acetate greater than arsenic greater than monosodium salicylate. This ranking and the results in general are in good agreement with what is known about these chemicals from other experiments with animals and from human experience. This battery of tests, or subsets thereof, may therefore have utility in the assessment of the potential neurobehavioral toxicity of various chemicals.

Acrylamides↗
PubMed1994

Synthesis and biological studies on some organo-tin and lead halo and mixed halo-pseudohalo anionic complexes.

Some new anionic complexes of organo-tin(IV) and lead (IV) isolated in combination of tetraorgano-ammonium phosphonium and stibonium cation(s). L[R4-nMXnY] and L2[R2MX2Y2], where R = C2H5, C4H9 or C6H5; M = Sn or Pb; X = Y = Cl = Br, I, N3, NCS; n = 1, 2 and L = R4M1 (M1 = N, P, Sb), whose structures were confirmed by correct elemental analyses, molar conductance values, van't Hoff factor and IR spectral studies, were synthesized and evaluated for anti-convulsant activity in vivo and antiviral and antibacterial activity in vitro. A few of them exhibited promising activity. In addition, the toxicity (ALD50) and effects on the central nervous system of these complexes have been studied in mice.

Animals↗
PubMedDate not supplied

[Immunotoxicology in occupational and environmental medicine: prospectives, limitations, and research objectives].

The immune system is able to recognize and neutralize potentially harmful agents, conferring to the organism resistance to infectious and malignant diseases. The authors have reviewed the literature and identified a group of substances able to enhance and/or reduce different immune functions, both in an experimental model and in occupational and environmental human exposure. The group includes several polyhalogenated hydrocarbons, particularly polychlorinated biphenyls, polybrominated biphenyls, tetrachloro-dibenzo-p-dioxin (TCDD), some metals like lead, cadmium and mercury, pesticides, i.e. dithiocarbamates and organotin compounds, organic solvents. The observed changes are usually slight and do not allow prognostic conclusion. In this study, the authors propose a 3-level rank of tests suitable for the immune evaluation of individuals occupationally exposed to xenobiotics, divided into three levels, as follows: tier 1: immunoglobulin classes (IgG, IgA, IgM), complement fractions (C3, C4), rheumatoid factor, and non-organ specific autoantibodies (AMA, SMA, ANA); CD3, CD4, CD8, CD57, CD20, HLA-DR; CD3/HLA-DR positive lymphocyte subsets; tier 2: determination of the mitotic response of peripheral blood lymphocytes to phytohaemoagglutinin, anti-CD3 monoclonal antibody, phorbol-myristate-acetate (PMA) and polyclonal immunoglobulin production after stimulation with pokeweed mitogen; tier 3: cytokine production with and without mitogen stimulation. The approach is "step by step" and assumes the need of a closely integrated and comparative evaluation of the findings obtained. The protocol could be used in research fields; moreover, some of the tests could be useful in the monitoring of persons exposed in the environment or in the workplace to immunotoxic substances or to biological agents.

Animals↗
PubMed1993

Crystal and molecular structure and in vitro antiproliferative and antitumor activity of two organotin (IV) carbohydrate compounds.

3-C-[(Triphenylstannyl)methyl]-1,2:5,6-di-O-isopropylidene-alpha-D -allofuranose (Ph3SnCH2 carbohydrate) and 3-C-(triphenylstannyl)-1,2:5,6-di-O-isopropylidene-alpha-D-allo furanose (Ph3Sn carbohydrate) were studied by diffraction methods, space groups P2(1)2(1)2(1), a = 6.073 (1), b = 13.091 (3), c = 37.739 (13) and a = 8.3219 (9), b = 11.876 (1), c = 29.575 (5) A, respectively; both compounds have distorted tetrahedral coordination. The biological study of these compounds along with Ph3SnCl shows the following: (a) With respect to their capacity to interfere with DNA, RNA, and protein synthesis of isolated fastly proliferating thymocytes, the triphenyltin carbohydrates are less active than Ph3SnCl. Protein synthesis was found to be most sensitive with an IC50 value of approximately 0.3 microM for Ph3SnCl, 3 microM for Ph3Sn-carbohydrate, and greater than 5 microM for Ph3SnCH2-carbohydrate; (b) The in vitro activity toward the mouse tumor cell lines MOPC315, P815, SL2, and L1210, which was also performed for Bu2SnCl2, also showed that the two triphenyltin carbohydrates were less effective than Ph3SnCl. From these results it is concluded that in vitro these Sn-C bonded triphenyltin carbohydrates are less active than Ph3SnCl. Ph3Sn carbohydrate is more active than Ph3SnCH2 carbohydrate, and this may be related with the long Sn-C (of the carbohydrate moiety) bond distance (2.225 (8) A) for the former compound. This compound shows a biological activity which is in contrast to the normal inactivity of tetraorganotins and is the first active member of this family whose molecular structure is reported.

Animals↗
PubMed1988

A comparison of the rates of methylation of mercury(II) species in aquatic media by various organotin and organosilicon moieties.

Metals can be methylated in environmental aqueous media by a variety of organotin and organosilicon compounds. Main group metals and metalloids were surveyed for the identification of species that can either donate or accept methyl groups. The methylation of mercury(II) by trimethyltin cation was found to be a bimolecular reaction, the reaction rate of which decreased with increasing chloride concentration. Kinetic investigations using NMR techniques showed that the most important pairs of reactants were (CH3)3Sn+ + HgCl2, (CH3)3SnCl + HgCl2, and (CH3)3SnCl + HgCl-3. Sodium 2,2,3,3-tetradeutero-3-(trimethylsilyl)propionate (TSP) and sodium 2,2-dimethyl-2-silapentane-5-sulfonate (DSS) were found to methylate mercury(II). Organylsilatranes were found to transfer their organic groups readily to mercury(II) to produce organomercury compounds.

Magnetic Resonance Spectroscopy↗
PubMed1967

Molluscicidal properties of organotin and organolead compounds.

Triphenyltin acetate has proved successful as a molluscicide in the laboratory and in small-scale field trials. However, in view of its cost and its toxicity to swamp rice at molluscicidal concentrations, an effort has been made to explore the molluscicidal value of other organotin and organolead compounds. Those that proved most toxic to snails were screened in the laboratory against swamp rice in order to obtain some measure of their phytotoxicity. This study yielded 6 compounds that were relatively non-toxic to rice. One of these, triphenyllead acetate, has been formulated as an emusifiable concentrate for use in the field and the results of trials in two parts of Tanzania are reported. Chemical analyses of water treated with triphenyllead acetate are discussed, and the reasons for the disappearance of the compound in the field are investigated. Some preliminary information on the toxicity of triphenyllead and triphenyltin derivatives to other organisms is also given.

Animals↗
PubMed2006

Synthesis characterization and biological study of diorganotin(IV) complexes of monomethyl phthalate.

The synthesis and characterization of new coordination compounds of some organotin(IV) chlorides with monomethyl phthalate is reported; the ligand molecules appear to be bound to the tin atom through carbonyl oxygen atoms. Their structures have been characterized by elemental analyses, molar conductance, and bonding in these complexes is discussed in terms of their IR, (1)H, (13)C, (119)Sn NMR and (119 m)Sn Mössbauer spectral studies. The spectroscopic results obtained are in full agreement with the proposed 2:1 stoichiometry. The complexes soluble in DMSO have been screened against a wide spectrum of bacteria and the results obtained are quite promising. The LD(50) values have also been determined in the albino rats. Some of the complexes also exhibit high anti-inflammatory activity.

Animals↗
PubMed1989

Inhibition of oxidative phosphorylation by organotin thiocarbamates.

A series of triphenyl-, tricyclohexyl- and tribenzyltin compounds have been synthesized and examined as inhibitors of mitochondrial oxidative phosphorylation. All compounds tested inhibit oxidative phosphorylation linked to succinate oxidation by potato tuber mitochondria. All of the organotin compounds inhibit ADP-stimulated O2 uptake linked to succinate oxidation with concentrations for 50% inhibition in the range 2-50 microM. This inhibition is not due to inhibition of electron transport from succinate to O2 per se: none of the organotin compounds at 50 microM substantially inhibit the rate of succinate oxidation in the presence of 2,4-dinitrophenol. Representative organotin compounds at 0.5-50 microM do not act as uncouplers of succinate oxidation. It is concluded that the organotin compounds act as energy transfer inhibitors to inhibit oxidative phosphorylation in potato tuber mitochondria. A similar mode of action of representative organotin compounds was found with rat liver mitochondria. These organotin compounds inhibit a hydrophobic Ca2+-dependent plant protein kinase in the absence but not in the presence of thiols.

Animals↗