Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Triethyltin 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 271 records · Page 15Linked to original sources
PubMed1975

The decrease of mitochondrial substrate uptake caused by trialkyltin and trialkyl-lead compounds in chloride media and its relevance to inhibition of oxidative phosphorylation.

1. In a 100 mM-KCl medium (pH 6.8) containing ATP, triethyltin (1 muM) causes a decrease in the uptake of pyruvate, malate, citrate or beta-hydroxybutyrate by rat liver mitochondria, but no decrease is observed in a 100 mM-KNO3 medium. This response is not modified by the presence of rotenone in the incubation medium. 2. In the KCl medium at least 1 muM-triethyltin is required to cause maximum inhibition of pyruvate uptake. 3. Trimethyltin, tributyltin and the trialkyl-lead analogues at 1 muM, to varying degrees, also cause a decrease in pyruvate uptake by mitochondria only in the KCl medium. 4. Triethyltin stimulates resting respiration of mitochondria with all the substrates tested in the KCl medium but not in the KNO3 medium, yet this stimulation of O2 uptake occurs under conditions when substrate uptake is decreased. 5. In contrast, both O2 uptake during state 3 respiration and ATP synthesis when linked to the oxidation of pyruvate, malate or citrate are strongly inhibited by 1 muM-triethyltin in a KCl medium, but O2 uptake and ATP synthesis during the oxidation of beta-hydroxybutyrate are only slightly affected. In a KNO3 medium O2 uptake and ATP synthesis linked to the oxidation of all substrates are only slightly affected. 6. The relevance of the decrease in substrate uptake by mitochondria caused by triethyltin in a KCl medium to the greater sensitivity of various mitochondrial functions observed in vitro is discussed. It is concluded that decrease of matrix substrate content is probably not the major cause of the greater sensitivity of oxidative phosphorylation to triethyltin in a KCl medium observed previously.

Adenosine Triphosphate↗
PubMed1977

Oxidative phosphorylation. Halide-dependent and halide-independent effects of triorganotin and trioganolead compounds on mitochondrial functions.

1. Each of five triorganotin and five triorganolead compounds was shown to perturb mithochondrial functions in three different ways. One is dependent and two are independent of Cl- in the medium. 2. Structure-activity relationships for the three interactions are described, and compounds suitable as tools for the separate study of each process are defined. 3. In a Cl- -containing medium trimethyltin, triethyltin, trimethyl-lead, triethyl-lead and tri-n-propyl-lead all produce the same maximum rate of ATP hydrolysis and O2 uptake; this rate is much less than that produced by uncoupling agents such as 2,4-dinitrophenol. 4. Increase in ATP hydrolysis and O2 uptake are measures on energy ultilization when triogranotin and triorganolead compounds bring about an exchange of external C1- for intramitochondrial OH- ions. Possible rate-limiting steps in this process are discussed. 5. In a C1- -containing medium ATP synthesis linked to the oxidation of beta-hydroxybutyrate or reduced cytochrone c is less inhibited by triethyltin or triethyl-lead than is ATP synthesis linked to the oxidation of succinate, pyruvate or L-glutamate. 6. The inhibition of ATP synthesis linked to the oxidation of both beta-hydroxybutyrate and reduced cytochrome c consists of two processes: one is a limited uncoupling and is C1- -dependent and the other is a C1- -independent inhibition of the energy-conservation system. 7. The different sensitivities to inhibition by triethyltin of mitochondrial functions involving the oxidation of beta-hydroxybutyrate and succinate are compared and discussed.

Adenosine Triphosphate↗
PubMed1999

Triorganotin compounds as antimicrobial agents.

Six triorganotin derivatives of thiolupinine(1-mercaptolupinane), 2-mercaptobenzoxazole and 2-mercaptobenzothiazole were prepared and tested against several bacteria, fungi and protozoa. Most compounds exhibited high activity against the tested microorganisms and particularly worth noting was the activity of triethyltin lupinylsulfide on Gram-negative strains. Triethylgermanium lupinylsulfide was also prepared but was devoid of action on the whole set of tested microorganisms.

Anti-Bacterial Agents↗
PubMed1991

Inhibition of Ca2+ transport associated with cAMP-dependent protein phosphorylation in rat cardiac sarcoplasmic reticulum by triorganotins.

Organotin compounds have been shown to interfere with cardiovascular system. We have studied the in vitro and in vivo effects of tributyltin bromide (TBT), triethyltin bromide (TET) and trimethyltin chloride (TMT) on the cardiac SR Ca2+ pump, as well as on protein phosphorylation of SR proteins, in order to understand the relative potency of these tin compounds. All the three tin compounds inhibited cardiac SR 45Ca uptake and Ca(2+)-ATPase in vitro in a concentration-dependent manner. The order of potency for Ca(2+)-ATPase as determined by IC50, is TBT (2 microM) greater than TET (63 microM) greater than TMT (280 microM). For 45Ca uptake, it followed the same order i.e., TBT (0.35 microM) greater than TET (10 microM) greater than TMT (440 microM). In agreement with the in vitro results, both SR Ca(2+)-ATPase and 45Ca uptake were significantly inhibited in rats treated with these tin compounds, indicating that these tin compounds inhibit cardiac SR Ca2+ transport. cAMP significantly elevated (70-80%) the 32P-binding to SR proteins in vitro in the absence of any organotin. In the presence of organotins, cAMP-stimulated 32P-binding to proteins was significantly reduced, but the decrease was concentration dependent only at lower concentrations. The order of potency is TBT greater than TET greater than TMT. In agreement with in vitro studies, cAMP-dependent 32P bound to proteins was significantly reduced in rats treated with TBT, TET and TMT. SDS-polyacrylamide gel electrophoresis of the cardiac SR revealed at least 30 Coomassie blue stainable bands ranging from 9 to 120 kDa.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1982

Effects of organotin compounds on maximal electroshock seizure (MES) responsiveness in mice. I. TRI(n-alkyl)tin compounds.

Male mice (25-30 g) were injected (ip) with 0, 3.5 X 10(-6), or 17.5 X 10(-6) mol trimethyltin bromide (TMT), triethyltin bromide (TET), tri-n-propyltin chloride (TPT), or tri-n-butyltin bromide (TBT) per kg. Additional groups of mice were also injected (ip) with either 0 or 17.5 X 10(-6) mol sodium bromide (NaBr) or 17.5 X 10(-6) mol stannic bromide (SnBr4) per kg. The mice were tested with maximal electroshock seizure (MES) at 0.5, 4, 21-24, and 96 h following exposure to the organotin compounds. Mice exposed to TMT, TET, TPT, or TBT exhibited dose-dependent decreases in MES severity as evaluated by seizure-grade distributions and duration of tonic seizure phases. The tri-n-alkyltin compounds exhibited a structure-activity relationship in their ability to decreased maximal responsiveness to the MES test. In order of decreasing ability they were: TMT greater than TET greater than TPT greater than TBT. Administration of NaBr and SnBr4 did not alter MES responsiveness, indicating the essential role of the alkyl moieties of the tri-n-alkyltin compounds in producing alterations in central nervous system function.

Animals↗
PubMedDate not supplied

Erythrocyte hemolysis by organic tin and lead compounds.

The effect of trialkyllead and trialkyltin on pig erythrocyte hemolysis has been studied and compared. The results of experiments showed that the hemolytic activity of organoleads increases with their hydrophobicity and follows the sequence: triethyllead chloride < tri-n-propyllead chloride < tributyllead chloride. And similarly in the case of organotins: triethyltin chloride < tri-n-propyltin chloride < tributyltin chloride. Comparison of the hemolytic activity of organoleads and organotins indicates that the lead compounds exhibit higher hemolytic activity. The methods of quantum chemistry allowed to determine the maximum electric potential of the ions R3Pb+ and R3Sn+, and suggest a relationship between the potential and toxicity.

Animals↗
PubMed1993

In vitro assessment of teratogenic potential of organotin compounds using rat embryo limb bud cell cultures.

Assessment of the relative teratogenic potential of bis(tri-n-butyltin)oxide (TBTO), tri-n-butyltin chloride (TBT), and its metabolites, i.e., (3-OH)hydroxybutyl dibutyltin chloride ((3-OH-Bu)DBT), di-n-butyltin dichloride (DBT), and butyltin trichloride (MBT) have been conducted using rat embryo limb bud cell cultures (LBC) to gain some knowledge of TBT embryotoxicity and DBT teratogenicity. Triphenyltin chloride (TPT), trimethyltin chloride (TMT), and triethyltin bromide (TET) have also been tested to obtain data for validation of LBC as a teratogen prescreening for organotin compounds. Fifty percent inhibition concentration for cell proliferation (IP50), and for cell differentiation (ID50), and the ratio of the former to the latter (P/D ratio) were obtained. The ID50 values in increasing order were as follows; TPT, DBT < TBT, TBTO < (3-OH-Bu)DBT < TET < TMT << MBT. With the exception of MBT, organotin compounds tested were very strong inhibitors of cell differentiation (ID50; 0.13-1.71 microM) and cell proliferation (IP50; 0.12-2.81 microM). P/D ratios for TBT, (3-OH-Bu)DBT, DBT and MBT were 1.0, 1.43, 1.32 and 1.08, respectively. These results suggest that the proximal toxin of DBT teratogenicity is DBT itself, and TBT is rather embryocidal than teratogenic so that TBT might mask the teratogenic and/or fetotoxic effects of its metabolites.

Abnormalities, Drug-Induced↗
PubMed1999

Differential gliotoxicity of organotins.

On the basis of reports that astrocytes play an important role in the neurotoxicity of trimethyltin (TMT), we investigated the sensitivity of astrocytes to TMT and compared it to triethyltin (TET), a neurotoxic analog with a different in vivo specificity. The gliotoxicity of these two compounds was further compared to that of tributyltin (TBT) and triphenyltin (TPT), two purportedly nonneurotoxic organotin compounds. The time and concentration components of organotin toxicity were determined by measuring lactate dehydrogenase (LDH) release and formazan production from dimethylthiazolyldiphenyltetrazolium bromide (MTT). A TMT concentration of 100 micromol/L did not elevate extracellular LDH until 48 h after exposure, while signs of toxicity were not seen at 72 h for concentrations less than 10 micromol/L. Extracellular LDH activity increased 24 h after exposure to concentrations of TET, TBT, and TPT as low as 2.5 micromol/L. TMT was the only organotin to produce a delayed cytotoxicity, requiring both higher concentrations and more time to produce discernible toxicity. In contrast with TBT and TPT, the toxicity of the two neurotoxic organotins (TMT and TET) produced an early increase in MTT reduction. The distinct pattern of toxicity for TMT does not explain its selective in vivo toxicity, but the lack of sensitivity of astrocytes to this organotin also does not rule out more subtle changes in these cells that could disrupt normal glial/neuronal interactions.

Animals↗
PubMed1974

Inhibition and uncoupling of photophosphorylation in isolated chloroplasts by organotin, organomercury and diphenyleneiodonium compounds.

1. Trialkyltin, triphenyltin and diphenyleneiodonium compounds inhibited ADP-stimulated O(2) evolution by isolated pea chloroplasts in the presence of phosphate or arsenate. Tributyltin and triphenyltin were the most effective inhibitors, which suggests a highly hydrophobic site of action. Phenylmercuric acetate was a poor inhibitor of photophosphorylation, which suggests that thiol groups are not involved. 2. Triethyltin was a potent uncoupler of photophosphorylation by isolated chloroplasts in media containing Cl(-), but had little uncoupling activity when Cl(-) was replaced by NO(3) (-) or SO(4) (2-), which are inactive in the anion-hydroxide exchange. It is suggested that uncoupling by triethyltin is a result of the Cl(-)-OH(-) exchange together with a natural uniport of Cl(-). Tributyltin, triphenyltin and phenylmercuric acetate had low uncoupling activity, probably because in these compounds the uncoupling activity is partially masked by inhibitory effects. 3. At high concentrations the organotin compounds caused inhibition of electron transport uncoupled by carbonyl cyanide m-chlorophenylhydrazone or NH(4)Cl. At these high concentrations the organotin compounds may be producing a detergent-like disorganization of the membrane structure. In contrast, diphenyleneiodonium sulphate inhibited uncoupled electron transport at low concentrations; however, this inhibition is less than the inhibition of photophosphorylation, which suggests that the compound also inhibits the phosphorylation reactions as well as electron transport. 4. The effects of these compounds on basal electron transport were complex and depended on the pH of the reaction media. However, they can be explained on the basis of three actions: inhibition of the phosphorylation reactions, uncoupling and direct inhibition of electron transport. 5. The inhibition of cyclic photophosphorylation in the presence of phenazine methosulphate by diphenyleneiodonium sulphate shows that it inhibits in the region of photosystem 1.

Adenosine Diphosphate↗
PubMed1985

Toxicity of triorganotin compounds: comparative in vivo studies with a series of trialkyltin compounds and triphenyltin chloride in male rats.

In 2-week feeding studies, a series of trialkyltin chlorides and triphenyltin chloride were fed to male weanling rats at different dietary concentrations to evaluate their toxic effects, especially on the brains and the lymphoid organs, thymus and spleen. The lower trialkyltin homologs, trimethyltin chloride (TMTC) and triethyltin chloride (TETC), were neurotoxic, causing neuronal degradation and cerebral edema, respectively, at dietary concentrations of 15 ppm. The intermediate homologs, tri-n-propyltin chloride (TPTC) and tri-n-butyltin chloride (TBTC), and the aromatic compound, triphenyltin chloride (TPhTC), caused a dose-related reduction of thymus weight. At a dietary concentration of 150 ppm decreases in thymus weight to 53, 39, and 81% of controls were found following treatment with TPTC, TBTC, and TPhTC, respectively. Microscopically, thymus atrophy was associated with a lymphocyte depletion in the thymic cortex. Only 16% of the total number of nucleated thymocytes could be isolated from rats fed 150 ppm TBTC. These effects were completely reversed within 2 weeks. Slight thymus atrophy was observed after feeding a relatively high dose of 150 mg tri-n-hexyltin chloride (THTC)/kg diet, whereas tri-n-octyltin chloride (TOTC) was ineffective. A dose-related decrease in spleen weight was noticed after 2 weeks feeding of TPTC, TBTC, and TPhTC. Liver weights were increased in rats fed TBTC, THTC, and TPhTC for 2 weeks. Nevertheless, no enlarged livers and normal spleen weights were found upon feeding 100 ppm TPTC or TBTC for 4 weeks, whereas thymus weight was severely decreased. Therefore, atrophy of the thymus was considered to be the predominant effect of the intermediate trialkyltins (TPTC, TBTC). From this study it is concluded that the lower trialkyltins (TMTC, TETC) are essentially neurotoxic, the intermediate trialkytins (TPTC, TBTC) and triphenyltin are primarily immunotoxic, and the higher homologs (THTC, TOTC) are only slightly toxic or not toxic at all.

Administration, Oral↗
PubMed2006

Development of an analytical method for organotin compounds in fortified flour samples using microwave-assisted extraction and normal-phase HPLC with UV detection.

The normal high-performance liquid chromatography with UV detection was applied for the determination of tributyltin chloride (TBT), triphenyltin chloride (TPhT), tetraphenyltin (TrPhT), triethyltin chloride (TET) and tetraethyltin (TrET) from flour samples. The separation was performed in the isocratic mode on cyanopropyl column with a mobile phase of hexane-acetonitrile-THF (97/1/2). Under the experimental conditions used, quantitative limit of TBT, TPhT, TrPhT, TET and TrET are 0.95, 0.46, 0.97, 0.75 and 0.96 microg/ml, respectively. Microwave-assisted extraction of organotin (OT) compounds at 100 degrees C with an extraction time of 3 min was described. The extraction of organotin can be finished in acetic acid-hexane (20/80) medium. The quantitative extraction of five organotin compounds was achieved with recoveries ranging from 88 to 101% R.S.D. 3-8%.

Analytic Sample Preparation Methods↗
PubMedDate not supplied

Comparison of the behavioral effects of neurotoxic and systemically toxic agents: how discriminatory are behavioral tests of neurotoxicity?

The behavioral effects of carbon tetrachloride-produced impairment of liver function, insulin-produced reduction of plasma glucose levels, and the reduction of food and water intake have been evaluated. Considerable similarity was found among the behavioral effects of systemically toxic agents, three neurotoxicants (triethyltin, acrylamide, and 2,5-hexanedione), and the neuroleptic drug haloperidol. Measure of motor strength differentiated neurotoxic from non-neurotoxic compounds, while measures of motor activity were equally sensitive to neurotoxic, systemically toxic, and non-neurotoxic agents. These findings demonstrate the importance of assessing systemic toxicity before drawing conclusions about the neurotoxicity of a behaviorally active compound.

Animals↗
PubMed1989

Correlation between behavioral and pathological changes in the evaluation of neurotoxicity.

Recently the EPA has implemented new guidelines under Section 4 of TSCA to undertake neurotoxicity testing. It is expected that other agencies, both national and international, will follow suit. The evaluation of neurotoxicity will be based primarily on behavioral and morphological observations and particularly on the correlation between them. Initially, considerable information will have to be gathered from various laboratories to form the background data on which decisions of toxic effects can be made. This paper presents our experience to date with behavioral and neuropathological procedures for the evaluation of chemical compounds or dietary regimens in rats for potential neurotoxicity. Reference is made to acrylamide, 2,5-hexanedione, 3,3'-iminodipropionitrile, amphetamine, physostigmine, ethanol, triethyltin, food and water deprivation, and carbon tetrachloride. The question of whether every change induced by xenobiotics can be considered as a sign of toxicity is discussed.

Acrylamide↗
PubMed1984

The 2-deoxyglucose uptake method as a first screen for neurotoxic compounds.

Our primary goal is to develop a screening procedure to detect and partially characterize neurotoxic compounds. There is a great need for a new approach to screening for neurotoxicants because our industrialized world abounds with untested and potentially neurotoxic compounds. A large number of new compounds are introduced each year. Although a number of testing approaches to the screening for neurotoxicants have been proposed in the recent years, a consensus on the most adequate approach is yet to emerge. The existing methods share a number of shortcomings. Thus, most methods only detect a fraction of the tested neurotoxicants. Other methods lack the necessary resolution to detect the neurotoxic damage reproducibly and reliably. Furthermore, many screening approaches are too time consuming and costly to be used for the large-scale screening of neurotoxicants. It is, therefore, imperative to develop reliable and efficient screening methods applicable in regulatory toxicology. In this report, we describe two versions of the same method that we feel may be very beneficial for the large-scale screening of neurotoxicants. The 2-deoxyglucose (2-DG) uptake method provides an indirect measure of neuronal activity in different areas of the brain. The ability of the method to detect most, if not all, neuroactive substances is reviewed in this report. In the context of this report, a neuroactive substance is defined as a substance acting directly on the central or peripheral nervous system neurons and (or) glia. The 2-DG method equals the sensitivity of the most sensitive alternative methods which were selectively designed to detect the effects of specific groups of compounds. The generality and sensitivity of the 2-DG method are of major importance. Thus, if a tested compound does not affect the uptake of 2-DG into the brain, it is not likely to be neuroactive. Since neurotoxic compounds are a subset of neuroactive compounds, a compound that is not neuroactive is also not neurotoxic. Thus, a single test may, in some instances, determine if a tested compound is nontoxic. In addition, it appears that each compound or, at least, each family of compounds produces a characteristic profile ("pattern") of the sites of altered 2-DG uptake. This pattern can be exploited to characterize the tested compound and help us decide whether it is neurotoxic or neuroactive. Preliminary results from our laboratory indicate classical neurotoxic agents such as acrylamide, triethyltin, and 2,5-hexanedione induce a generalized depression of the 2-DG uptake throughout the brain.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1977

Studies of energy-linked reactions. Localization of the site of action of trialkyltin in yeast mitochondria.

Ligand-binding studies with labelled triethyltin on yeast mitochondrial membranes showed the presence of high-affinity sites (KD = 0.6 micronM; 1.2 +/- 0.3 nmol/mg of protein) and low-affinity sites (KD less than 45 micronM; 70 +/- 20 nmol/mg of protein). The dissociation constant of the high-affinity site is in good agreement with the concentration of triethyltin required for inhibition of mitochondrial ATPase (adenosine triphosphatase) and oxidative phosphorylation. The high-affinity site is not competed for by oligomycin or venturicidin, indicating that triethyltin reacts at a different site from these inhibitors of oxidative phosphorylation. Fractionation of the mitochondrial membrane shows a specific association of the high-affinity sites with the ATP synthase complex. During purification of ATP synthase (oligomycin-sensitive ATPase) there is a 5-6-fold purification of oligomycin- and triethyltin-sensitive ATPase activity concomitant with a 7-9-fold increase in high-affinity triethyltin-binding sites. The purified yeast oligomycin-sensitive ATPase complex contains approximately six binding sites for triethyltin/mol of enzyme complex. It is concluded that specific triethyltin-binding sites are components of the ATP synthase complex, which accounts for the specific inhibition of ATPase and oxidative phosphorylation by triethyltin.

Adenosine Triphosphatases↗
PubMed1996

The structure of organometals determines cytotoxicity and alteration of calcium homeostasis in HL-60 cells.

There is increasing concern about the degradation and metabolisation as well as the biochemical mechanisms of action of organometallic compounds. They are known to be immunotoxic and/or neurotoxic. Because of their different toxic capacities, the development of a reliable correlation between molecular parameters and biochemical effects, which could be helpful in risk assessment, was an aim of this study. The tested organolead and -tin compounds decrease the viability of human cells in culture in a time- and concentration-dependent manner. Parabolic QSAR(1)(1) The abbreviations used are: TMT, trimethyltin chloride; TET, triethyltin bromide; TPT, tripropyltin chloride; TBT, tri- n-butyltin chloride; DBT, di- n-butyltin dichloride; TEL, triethyllead chloride; DEL, diethyllead dichloride; TML, trimethyllead chloride; TPhL, triphenyllead chloride; QSAR, quantitative structure-activity relationships; TSA, total surface area; MW(ion), ionic molecular weight; fMLP, N-formyl-L-methionyl-L-leucyl-L-phenylalanine; fluo-3, fluo-3 free acid; fluo-3 AM, fluo-3 acetoxymethyl ester; Me(2)SO, dimethyl sulfoxide; PLA(2), phospholipase A(2) (EC 3.1.1.4); FCS, fetal calf serum; HEPES, 4-(2-hydroxy-ethyl)-1-piperazineethanesulfonic acid; EGTA, [ethylene-bis(oxyethylenenitrilo)]tetraacetic acid; [Ca(2+)](i), cytosolic free Ca(2+) concentration models yield an adequate correlation between toxicity expressed as LC(50) and structural parameters like ionic molecular weight (MW(ion)) or total surface area (TSA). Two main chemical attributes of the organometals are probably responsible for such a parabolic relationship: the hydrophobic side chain and the polar metal atom. Furthermore, all tested organometal compounds evoke a persistent increase of the cytosolic free calcium concentration [Ca(2+)](i). This effect is mainly due to an influx from the extracellular space. Further results suggest that Ca(2+) enters the cell via opened calcium channels. Based on the essential role of Ca(2+) within cellular signalling, the perturbation of calcium homeostasis appears to be an important event in final cell killing by organometals and it is most likely that other biochemical mechanisms, e.g. activation of phospholipase A(2), are possibly mediated by an increase of [Ca(2+)](i).

Journal Article↗