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PubMed1981

The microsomal metabolism of the organometallic derivatives of the group-IV elements, germanium, tin and lead.

The NADPH- and oxygen-dependent microsomal metabolism of the di-, tri- and tetra-ethyl-substituted derivatives of germanium, tin and lead was shown to give rise to ethylene as a major product and ethane as a minor product. These reactions were shown to be catalysed by the liver microsomal cytochrome P-450-dependent mono-oxygenase. Since formation of ethane and ethylene was differentially inhibited by anaerobiosis, the results suggest that at least a large portion of the ethane produced may be derived by a reductive mechanism. Triethyltin bromide in both the absence and presence of NADPH was shown to convert cytochrome P-450 into cytochrome P-420 and to affect the function of the mono-oxygenase in vitro. Tetraethyltin caused the NADPH- and time-dependent formation of cytochrome P-420, suggesting that tetraethyltin is converted into triethyltin salts in significant concentrations. The order of potency in formation of cytochrome P-420 was closely paralleled by the ability of the tin derivatives to induce microsomal lipid peroxidation in vitro.

Animals↗
PubMed1998

Sequence, catalytic properties and expression of chicken glutathione-dependent prostaglandin D2 synthase, a novel class Sigma glutathione S-transferase.

The Expressed Sequence Tag database has been screened for cDNA clones encoding prostaglandin D2 synthases (PGDSs) by using a BLAST search with the N-terminal amino acid sequence of rat GSH-dependent PGDS, a class Sigma glutathione S-transferase (GST). This resulted in the identification of a cDNA from chicken spleen containing an insert of approx. 950 bp that encodes a protein of 199 amino acid residues with a predicted molecular mass of 22732 Da. The deduced primary structure of the chicken protein was not only found to possess 70% sequence identity with rat PGDS but it also demonstrated more than 35% identity with class Sigma GSTs from a range of invertebrates. The open reading frame of the chicken cDNA was expressed in Escherichia coli and the purified protein was found to display high PGDS activity. It also catalysed the conjugation of glutathione with a wide range of aryl halides, organic isothiocyanates and alpha,beta-unsaturated carbonyls, and exhibited glutathione peroxidase activity towards cumene hydroperoxide. Like other GSTs, chicken PGDS was found to be inhibited by non-substrate ligands such as Cibacron Blue, haematin and organotin compounds. Western blotting experiments showed that among the organs studied, the expression of PGDS in the female chicken is highest in liver, kidney and intestine, with only small amounts of the enzyme being found in chicken spleen; in contrast, the rat has highest levels of PGDS in the spleen. Collectively, these results show that the structure and function, but not the expression, of the GSH-requiring PGDS is conserved between chicken and rat.

Amino Acid Sequence↗
PubMed2000

Molecular mechanisms of apoptosis induced by cytotoxic chemicals.

The purpose of this review article is to discuss established molecular mechanisms of apoptosis and their relevance to cell death induced by environmental toxicants. Apoptosis is a highly regulated form of cell death distinguished by the activation of a family of cysteine-aspartate proteases (caspases) that cleave various proteins resulting in morphological and biochemical changes characteristic of this form of cell death. Abundant evidence supports a role for mitochondria in regulating apoptosis. Specifically, it seems that a number of death stimuli target these organelles and stimulate, by an unknown mechanism, the release of several proteins, including cytochrome c. Once released into the cytosol, cytochrome c binds to its adaptor molecule, Apaf-1, which oligomerizes and then activates pro-caspase-9. Caspase-9 can signal downstream and activate pro-caspase-3 and -7. The release of cytochrome c can be influenced by different Bcl-2 family member proteins, including, but not limited to, Bax, Bid, Bcl-2, and Bcl-X(L). Bax and Bid potentiate cytochrome c release, whereas Bcl-2 and Bcl-X(L) antagonize this event. Although toxicologists have traditionally associated cell death with necrosis, emerging evidence suggests that different types of environmental contaminants exert their toxicity, at least in part, by triggering apoptosis. The mechanism responsible for eliciting the pro-apoptotic effect of a given chemical is often unknown, although in many instances mitochondria appear to be key participants. This review describes our current understanding of the role of apoptosis in environmental toxicant-induced cell death, using dioxin, metals (cadmium and methylmercury), organotin compounds, dithiocarbamates, and benzene as specific examples. Finally, we conclude with a critical discussion of the current knowledge in this area and provide recommendations for future directions.

Animals↗
PubMed2002

Preventable exposure to trimethyl tin chloride: a case report.

Trimethyl tin chloride (TMTC) is a highly toxic organotin compound that affects four main target organs: the brain, liver, immune system and skin. Exposure can occur by inhalation, ingestion or direct skin absorption. Trimethyl tin is but one of many hazardous substances with potentially serious health consequences to which individuals working in research laboratories may be exposed. We report a preventable case of TMTC exposure. Better understanding of the Canadian Workplace Hazardous Materials Information System (WHMIS) legislation and its applicability to the research laboratory situation would prevent such unnecessary exposure to hazardous substances.

Adult↗
PubMed1988

DCCD-sensitive Na+-transport in the membrane vesicles of Halobacterium halobium.

The effects of N,N'-dicyclohexylcarbodiimide (DCCD) and various ionophores on light-induced 22Na+-transport were studied in right-side-out membrane vesicles from Halobacterium halobium R1M1. The light-induced Na+ efflux was inhibited at the same DCCD concentration (greater than 40 nmol/mg protein) as required for inhibition of the Na+-dependent membrane potential (delta phi) formation. This supports our previous indication that the DCCD-sensitive, Na+-dependent transformation of pH-gradient (delta pH) into delta phi is mediated by Na+/H+-antiporter (Murakami, N. and Konishi, T. (1985) J. Biochem. 98, 897-907). FCCP or a combination of valinomycin and triphenyltin (TPT) inhibits the light-induced Na+ efflux in accordance with the notion of protonmotive force (delta mu H+)-driven antiporter. However, a marked lag in initiation of the Na+ efflux occurred in the presence of valinomycin, TPMP+, or a small amount of FCCP, suggesting that a gating step is involved in the Na+ efflux. On the other hand, the delta pH-dissipating ionophore TPT did not cause the lag. A simultaneous determination of delta phi, delta pH, and Na+ efflux rate at the initial stage of illumination revealed that the antiporter is gated by delta phi rather than delta mu H+.

Biological Transport↗
PubMed1981

Tin and tin-resistant microorganisms in chesapeake bay.

Sediment and water samples from nine stations in Chesapeake Bay were examined for tin content and for microbial populations resistant to inorganic tin (75 mg of Sn liter as SnCl(4).5H(2)O) or to the organotin compound dimethyltin chloride [15 mg of Sn liter as (CH(3))(2)SnCl(2)]. Tin concentrations in sediments were higher (3.0 to 7.9 mg kg) at sites impacted by human activity than at open water sites (0.8 to 0.9 mg kg), and they were very high (239.6 mg kg) in Baltimore Harbor, which is impacted by both shipping and heavy industry. Inorganic tin (75 mg Sn liter) in agar medium significantly decreased viable counts, but its toxicity was markedly reduced in liquid medium; it was not toxic in medium solidified with silica gel. Addition of SnCl(4).5H(2)O to these media produced a tin precipitate which was not involved in the metal's toxicity. The data suggest that a soluble tin-agar complex which is toxic to cells is formed in agar medium. Thus, the toxicity of tin depends more on the chemical species than on the metal concentration in the medium. All sites in Chesapeake Bay contained organisms resistant to tin. The microbial flora was more sensitive to (CH(3))(2)SnCl(2) than to SnCl(4).5H(2)O. The elevated level of tin-resistant microorganisms in some aeas not containing unusually high tin concentrations suggests that factors other than tin may participate in the selection for a tin-tolerant microbial flora.

Journal Article↗
PubMed1986

Effect of triethyltin on enzyme activity in human adult and cord red cells.

Since organotin compounds represent an environmental health hazard, we determined the effect of triethyltin bromide (TTB) on red blood cell (RBC) enzyme activity. TTB produced a concentration-dependent inhibition of hexokinase and pyrimidine 5'-nucleotidase for both adult and cord RBC. D-Glucose, but not ATP or MgCl2, prevented the hexokinase inhibition by TTB. Glucose-6-phosphate dehydrogenase, adenylate kinase, and hypoxanthine-guanine phosphoribosyltransferase were also inhibited by TTB. Cord RBC enzymes were more resistant to the effects of TTB than were adult RBC enzymes. Although TTB is a potent inhibitor of hexokinase, physiologic concentrations of glucose appear to protect the RBC during clinical tin intoxication.

5'-Nucleotidase↗
PubMed1999

[Marine natural products influencing larval settlement and metamorphosis of marine sessile organisms].

Most marine sessile organisms have a planktonic larval phase in their life cycles, and then larvae settle and metamorphose into their adult forms. The selection of settlement sites is a critical event for these organisms because settlement on unsuitable places affects their survivorship severely. Ascidians live gregariously, and conspecific chemical cues are thought to play an important role in gregarious settlement of larvae. The extracts of conspecific adults or larvae have been claimed to contain "natural metamorphosis inducers." Little is known, however, about their chemical properties. To discover natural signal substances for larval metamorphosis in ascidians, we surveyed the metamorphosis-inducing activity of the medium conditioned by ascidian larvae, and succeeded in isolating a metamorphosis-inducing substance from the conditioned medium of Halocycthia roretzi larvae and found that it was identical to lumichrome. We have also isolated more than 40 active metabolites, which may mimic lumichrome, from marine sponges. On the contrary, marine sessile organisms cause serious problems by settling on fishing nets, hulls of ships, and cooling systems of power plants. Organotin compounds have been widely used for the control of these organisms, but they are known to be toxic to marine biota. Therefore, nontoxic antifouling substances are urgently needed. Marine sessile organisms possess chemical defense systems using their secondary metabolites, which might be potential by nontoxic antifouling agents. We have attempted to obtain antibarnacle substances from marine sponges and isolated 26 antifoulants.

Animals↗
PubMed2002

Quantitative analysis of triphenylboron in environmental water samples by liquid chromatography/mass spectrometry.

Liquid chromatography/mass spectrometry (LC/MS) has been applied to the analysis of triphenylboron, which has been produced as a substitute for organotin compounds, in water. Although commercial triphenylboron compounds are produced as pyridinyl complexes, the chemical form in water is supposed to be mainly triphenylboron after liberating pyridine. The triphenylborons were extracted from water with an Empore C18 extraction disk under acidic condition, and the extracts were introduced directly into a liquid chromatograph-mass spectrometer equipped with a negative ion electrospray ionization interface. Identification of the compounds was performed with specific ions produced from the triphenylboron, and a quantitative analysis was carried out using the peak areas. The average recoveries from distilled water, seawater and river water at 0.30 ng/ml were 92.3, 100 and 85.3%, respectively. A detection limit of 0.023 ng/ml for triphenylboron was achieved.

Boron Compounds↗
PubMedDate not supplied

Encapsulation of triphenyltin hydroxide.

Triphenyltin hydroxide was encapsulated to prolong its fungicidal activity and to decrease its phytotoxicity in peanut fields. The envelopes found to be adequate for this purpose were polyureas and ethyl cellulose, as was demonstrated by biological tests.

Cellulose↗
PubMed1995

Tributyltin use in interior paints: a continuing health hazard.

We report on five patients who developed mucous membrane irritation after inhalational exposure to an interior use latex paint containing the organotin compound bis(tributyltin) oxide. Stricter regulations regarding the use of bis(tributyltin) oxide with interior paint would most likely have prevented these cases of tributyltin toxicity. Bis(tributyltin) oxide should not be used with paint intended for interior use.

Adult↗
PubMedDate not supplied

[Occupational agents and endocrine function: an update of the experimental and human evidence].

Many environmental and occupational agents have been shown to cause detrimental effects on endocrine function and growing scientific evidence supports the hypothesis that such alterations may produce serious consequences for health. Although those chemicals mimicking (or contrasting) estrogenic or androgenic actions have raised great concern, the relevance of disruption of other hormonal pathways is not negligible. This article reviews the effects of chemical and physical agents on the hypothalamus-pituitary unit, pineal gland, thyroid, parathyroid and calcium metabolism, adrenal glands, and glucose metabolism. Metals (Pb, Mn, Cd, organotin compounds), solvents (benzene, dioxane, styrene, tetrachloroethylene, toluene), organochlorines (PCBs, TCDD), and physical agents have been shown in human, animal or in vitro studies to cause alterations of the blood levels, and of the activity or circadian rhythm of pituitary hormones. Melatonin has been proposed as the link between environmental/occupational factors and the immunologic and neoplastic diseases, which in addition to disturbances of the circadian timing system, feature pineal hormone reduction. Thyroid gland diseases (goiter, autoimmune thyroiditis, carcinoma) are associated with exposure to many chemical or physical agents. Disruptions of calcium control secondary to metal exposures, as well as the effect of radiation on parathyroid, are addressed. Adrenal cortex and medulla function alterations by several chemical agents are considered. Finally, diabetes mellitus as an outcome of occupational or environmental exposures and as susceptibility to occupational and environmental factors is discussed.

Animals↗
PubMed2001

[Effects of microwave radiation on the content of five elements in mice bone tissue].

Mice were radiated with 2450 MHz, 10 mW/cm2 microwave for 12 days, 1.5 h/day. After microwave radiation, compared with the normal control, the content of calcium and zinc in mice bone were significantly decreased (P < 0.05) copper, iron and manganese decreased, appulsively After Libido, a composed traditional herb medicine, and asshide asafetida were supplied seperatively, the content of calcium and trace element zinc in mice bone increased (P < 0.05). It is concluded that Libido was effective on the resistance of mice to microwave radiation. The toxicity of organotin compounds and the current pollution status.

Animals↗
PubMed2003

[Di-n-butytin tridentate acylhydrazone Schiff base complexes: synthesis and studies by infrared spectroscopy].

Four tridentate acylhydrazone schiff base ligands H2L [H2L1:C6H5C(O)NHN = CHC6H4OH-2, H2L2:C6H5C(O)NHN = CHC6H3(OH)(2)-2,4, H2L3:NC5H4C(O)NHN = CHC6H4OH-2, H2L4:NC5H4C(O)NHN = CHC6H3(OH)(2)-2,4] were synthesized and use to form four novel di-n-Butytin complexes of the type (n-Bu)2SnL with di-n-Butytin oxide [(n-Bu)2SnO]. All these ligands and complexes were characterized by elemental analysis and infrared spectroscopy. Their principal infrared spectral absorption peaks were assigned and discussed for the region of 4,000-400 cm-1. A comparison of the infrared spectra of the ligands with those of the corresponding complexes reveals that the disappearance of the bands assigned to carbonyl unambiguously confirms that the ligands coordinate with tin in the enol form. The coordination manner for tridentate acylhydrazone schiff base ligands with tin atom in the complexes was determined. The results indicated that the Sn atom in these complexes is five-coordinated.

Hydrazones↗