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At least 127 records · Page 7Linked to original sources

PubMed1986

Effects of chemicals on delayed matching behavior in pigeons. III. Effects of triethyltin.

The effects of triethyltin (TET) on delayed matching-to-sample performance were studied in male White Carneaux pigeons. Pigeons were trained to peck a red or green center key 15 times to turn it off. After a 2- or 5-sec delay, one side key was illuminated by a red color and the other by a green color. One peck on the side key whose color matched the color that the center key had been, produced food. After performance had stabilized, TET was administered intramuscularly at 3 different dosages (1.75, 3.0 and 5.6 mg/kg) to 3 different groups of birds. Birds received 4 injections of the same dose 2 weeks apart. Responding was totally suppressed in all animals 3 hours after each TET administration at all dosage levels. At 27 and 51 hrs after TET administration, dose-dependent decreases in both matching accuracy and rate of responding were observed. These behavioral changes disappeared in 2 to 3 days.

Animals↗

PubMedDate not supplied

Triethyltin: ambient temperature alters visual system toxicity.

Previous studies have indicated that acute exposure to triethyltin (TET) increases latencies of the flash evoked response (VER) recorded from the rat cortex. TET also produces hypothermia, which may be modified by altering environmental (ambient) temperature. In this study, the role of ambient temperature in determining the effects of acute TET upon the VER was examined. Rats with chronically implanted electrodes were administered either TET (6 mg/kg) or saline, and maintained in either a warm (30 degree C) or cool (22 degrees C) environment for the next 7 hrs. VERs were recorded during this 7 hr period, and at regular intervals for the next 2 weeks. TET increased VER peak latencies. VER peak latencies recorded from animals exposed in a cool room gradually returned to pre-TET values. Latencies recorded from animals exposed to TET in a warm room remained elevated for a longer period of time, thus indicating a more severe impact of the TET exposure. This study indicates that toxicant-induced alterations in core temperature are potential determinants of other toxicant-induced effects.

Animals↗

PubMed1984

Histopathology of spinal cord, peripheral nerve, and soleus muscle of rats treated with triethyltin bromide.

Mammalian exposure to triethyltin (TET) leads to severe impairment of motor function. Spinal cord, rootlets of spinal nerve, sciatic nerve, and soleus muscle of TET-treated rats were examined to assess their involvement. Adult rats were exposed to TET bromide in drinking water (30 mg/liter) for 3 weeks. The spinal cord became edematous with vacuolar formation in the myelin of white and gray matter. Chromatolysis occurred in motor neurons of the ventral root. Myelin of ventral and dorsal rootlets of spinal nerve was also affected with ventral rootlets showing greater involvement. Minimal effect was seen in myelin of sciatic nerve. Soleus muscle contained atrophic myofibers and, after 3 weeks recovery, type-grouping of fast-twitch myofibers. Chromatolysis and type-grouping were regarded as indications of a degenerative effect of TET-treatment on peripheral axons. We conclude that the neuromuscular toxicity of TET has a myopathic and neuropathic component and that the involvement of the neuronal cell body and the denervation of myofibers may contribute to the peripheral motor dysfunction.

Animals↗

PubMedDate not supplied

Effects of triethyltin on ingestive behavior at ad lib, reduced, and recovered body weight.

The effects of repeated injections of small amounts of the neurotoxicant triethyltin (TET) on 1 and 24 hr food and water intake were investigated in rats at ad lib feeding, reduced, and recovered body weights. Following adaptation to 15% ethanol vehicle injections, TET doses of 0.5, 1.0 and 1.5 mg/kg body weight were administered in four separate injections, each separated by 3 or 4 days. Decreases only in 24 hr food intake and body weight occurred with 1.5 mg/kg TET in ad lib feeding animals. In animals reduced to 80% body weight decreases in water intake occurred for only 1 hr after injections of 1.0 or 1.5 mg/kg TET. When TET was administered to animals previously reduced to 80% body weight and allowed to recover ad lib feeding weight, effects on daily food and water intakes were observed. The effects of TET on ingestive behavior seem to be dependent on whether or not animals are or have been chronically food deprived. Results are discussed in terms of the known effects of TET on brain physiology.

Analysis of Variance↗

PubMed1981

Neonatal triethyltin exposure alters adult electrophysiology in rats.

In adults, triethyltin (TET) produces degeneration of white matter, edema, vacuolization on myelin and histotoxic hypoxia. To determine the functional consequences of perinatal exposure to TET, albino rats were administered either 0, 3, 6, or 9 mg/kg TET on postnatal day 5. Upon reaching adulthood, the rats were implanted with electrodes for recording visual evoked potentials (VEPs) and hippocampal afterdischarges (ADs). In addition to these tests, 17 days of kindling trials were administered to the rats followed by testing with pentylenetetrazol and picrotoxin for seizure susceptibility. TET increased latencies of P2, P3, and N3 of the VEP in a dose dependent fashion. TET also decreases N1P2 amplitudes and produced gender-specific alterations in both P1, N1, and N2 latencies and N2P3 amplitudes. TET produced alterations in duration of the AD recorded from cortex during kindling, but did not produce significant alterations in any of the other variables tested. The results support previous studies, since they show that the adult VEP is sensitive to perinatal toxicant exposure.

Analysis of Variance↗

PubMedDate not supplied

Pharmacological and biochemical evaluation of triethyltin's anticonvulsant effects.

Acute treatment of mice with triethyltin (TET) causes dose dependent anticonvulsant effects as determined by the maximal electroshock (MES) test: grade 1 (minimal) to grade 5 (maximal) seizures. Thirty minutes following 1 or 5 mg/kg TET mice exhibit 20% grade 4 and 80% grade 5 seizures or 90% grade 2 and 10% grade 3 seizures, respectively. These studies were designed to examine the neuropharmacological and neurochemical basis of this anticonvulsant effect. For MES testing, mice were injected with either reserpine, yohimbine, propranolol, haloperidol or metergoline prior to dosing with TET. Only reserpine and yohimbine blocked the previously noted anticonvulsant effects of TET. For chemical seizure testing, bicuculline ad picrotoxin were injected 30 minutes following TET. TET significantly decreased the convulsant effects of these GABAergic blockers. These results are interpreted to mean that TET preferentially interacts with the alpha-adrenergic and GABAergic transmitter systems to produce its anticonvulsant effects. In vitro receptor binding assays revealed no direct agonist activity of TET at either of these two sites. Possible alternative mechanisms are discussed.

Analysis of Variance↗

PubMed1984

Tin distribution in adult rat tissues after exposure to trimethyltin and triethyltin.

The time course of distribution of tin in the adult rat was determined in brain, liver, kidneys, heart, and blood following single ip administrations of trimethyltin hydroxide (TMT) and triethyltin bromide (TET). Adult Long-Evans rats were killed 1, 4, 12, and 24 hr, and at 5, 10, or 22 days following injection of TMT and TET (N = 6/time), and tissues were analyzed for total tin by atomic absorbance spectroscopy. TET exposure resulted in higher tin concentrations in brain, liver, and kidney tissues, while the two trialkyltins resulted in approximately equal tin concentrations in the heart and blood. Rates of elimination of tin (expressed as elimination rate constants, Kel) were greater in all tissues following TET exposure than following TMT exposure. The concentration of tin in the brain 12 hr after TMT exposure was 4.4, 8.5, and 12.7 ng tin/mg protein for dosages of 3.0, 6.0, and 9.0 mg/kg, respectively. Tin was evenly distributed across the cerebellum, medulla-pons, hypothalamus, hippocampus, and striatum following TMT exposure. These results describe major differences in the disposition and rates of elimination of tin from body tissues after TMT and TET exposure, and demonstrate that the regional disposition of tin is not related to the region-specific pathology reported following TMT exposure.

Animals↗

PubMedDate not supplied

Effects of triethyltin and its interaction with d-amphetamine and chlorpromazine on responding under a multiple schedule of food presentation in rats.

Effects of triethyltin (TET) were studied in rats performing under a multiple fixed-ratio 30 fixed-interval 5-min schedule of food presentation. A dose of 1.0 mg/kg TET produced only marginal effects on responding. A dose of 3.0 mg/kg suppressed responding 3 hours after administration, but responding returned to control levels by the next day. During a period 2 to 6 weeks after the 3.0 mg/kg dose, small rate increases were observed for fixed-interval responding. The 5.6 mg/kg dose eliminated responding under both schedule components and all the animals died on the fourth day. Rats were also given d-amphetamine and chlorpromazine before and beginning six weeks after 1.0 and 3.0 mg/kg TET treatment. Both doses of TET attenuated the rate-increasing effect of d-amphetamine on fixed-interval responding, but d-amphetamine dose-effect curves determined before and after TET administration differed significantly only for 3.0 mg/kg dose of TET. Chlorpromazine dose-effect curves did not differ significantly before and after TET treatment.

Animals↗

PubMedDate not supplied

Triethyltin exposure suppresses synaptic transmission in area CA1 of the rat hippocampal slice.

To examine the effects of TET on the electrophysiology of area CA1 of hippocampus, hippocampal slices were obtained from adult hooded rats and were maintained in vitro using standard techniques. Stimulating and recording electrodes were placed in the Schaffer collaterals and CA1 pyramidal cell body layer, respectively. Following baseline measurements, slices were exposed to either 0, 1, 3, 6, or 10 microM TET in the incubating medium. Both pyramidal cell excitability and recurrent/feedforward inhibition were suppressed in a dose-dependent manner within 3 hr postexposure. The evoked population spike and population excitatory postsynaptic potential (EPSP) were suppressed significantly by 2 hr postexposure for 1 and 3 microM TET exposures, and by 45 min postexposure for 6 and 10 microM exposures. A similar dose-dependency was observed for the suppression of recurrent/feedforward inhibition in hippocampal CA1. A second procedure tested the specificity of TET effects to axonal conduction of Schaffer collaterals. Both the stimulating and recording electrode were placed in the Schaffer collaterals so that both the Schaffer collateral population fiber volley and the CA1 pyramidal cell population EPSP could be recorded. TET exposure suppressed pyramidal cell EPSPs without significantly affecting the amplitude of Schaffer collateral fiber volleys. The results support the view that acute TET exposure suppresses synaptic transmission in area CA1 of hippocampus.

Animals↗

PubMedDate not supplied

Triethyltin intoxication alters acetylcholine release from rat phrenic nerve-hemidiaphragm.

Triethyltin (TET) exposure produces, among other symptoms, muscular weakness . The etiology of this phenomenon is obscure, but the symptoms suggest impaired cholinergic transmission at the neuromuscular junction. Therefore, acetylcholine (ACh) release was assessed in the vascularly perfused phrenic nerve-hemidiaphragm isolated from rats subjected to acute or chronic in vivo exposure to TET. Adult male hooded Long-Evans rats (250-350 grams) were exposed acutely to one injection of TET (10 mg/kg IP), or chronically to TET (30 mg/L) in their drinking water. Hemidiaphragms were obtained from treated and age-matched control rats 24 hours after acute exposure or one, two, or three weeks after initiation of the chronic exposure regimen. ACh release was assessed during unstimulated (spontaneous), stimulated (7 Hz), and supra-stimulated (20 Hz) conditions. Ach release was not altered in the hemidiaphragms of acutely exposed rats. Rats chronically exposed to TET showed normal spontaneous release, a trend towards decreased stimulated (7 Hz) release, and an almost complete failure to release Ach in response to 20 Hz stimulation. The data are discussed with respect to known TET effects on cellular bioenergetics and the consequences for neurotransmitter synthesis and release mechanisms.

Acetylcholine↗

PubMedDate not supplied

Chronic triethyltin exposure reduces the resting membrane potential of rat soleus muscle.

Muscle weakness is a prominent component of the toxic syndrome which results from prolonged exposure to triethyltin (TET). The etiology of this phenomenon includes, in part, an alteration of acetylcholine (ACh) release from motoneurons but there are also indications that TET causes a primary myopathy. We have found that chronic exposure of rats to TET bromide (30 mg/liter of drinking water) caused a time-dependent reduction of resting membrane potentials (RMPs) recorded in situ from soleus muscle fibers. The RMPs of TET-exposed rats were significantly lower than those of control animals (5.4 mV) after four days and were further reduced by continuous TET exposure to 11.2 mV less than control on the twenty-eighth day. Three weeks after rats were withdrawn from TET RMPs were restored to control values. TeT had no effect on the frequency, amplitude or incidence of occurrence of miniature endplate potentials. Spontaneous ACh release ane its action on the postsynaptic membrane were not affected by TET, which suggests that TET reduces RMPs through an effect on muscle fibers unrelated to denervation. We propose that TET reduces RMPs by inhibiting the bioenergetic capacity of the muscle and that this myogenic toxicity is a significant factor in the development of muscle weakness following exposure.

Animals↗

PubMed1990

Isolation and genetic study of triethyltin-resistant mutants of Saccharomyces cerevisiae.

Three mutants of Saccharomyces cerevisiae resistant to triethyltin (an inhibitor of mitochondrial ATPase) on non-fermentative media, and non-resistant to this drug on fermentative media, were isolated and named TTR1, TTR2 and TTR3. Apart from triethyltin resistance, these mutants show the following common characteristics: (1) Increased intracellular cytochrome c concentration. (2) Increased respiration rate. (3) Decreased growth yield. (4) Increased growth sensitivity to several drugs inhibiting oxidative phosphorylation: namely, CCCP (permeabilizing inner mitochondrial membrane to protons), valinomycin (permeabilizing inner mitochondrial membrane to potassium) and oligomycin (inhibitor of mitochondrial ATPase). (5) Increased sensitivity to carbon source starvation. For each mutant, these characteristics appeared to be due to a single pleiotropic nuclear mutation. Mutation TTR1 causes additional phenotypic characteristics which do not appear in mutants TTR2 and TTR3: (1) Pinkish coloration of colonies which is more pronounced after a long growth period. (2) Inability of the cells to store glycogen. (3) Growth defect of the cells on a galactose-containing medium. (4) Inability of a diploid homozygote mutant strain to sporulate. All these phenotypic characteristics have already been described in yeast mutants deregulated in cAMP-dependent protein phosphorylation. Crossing of a strain bearing the TTR1 mutation with a strain mutated in the adenylate cyclase structural gene suggested that the TTR1 phenotype is due to a modification in regulation of cAPK by cAMP, making cell multiplication possible without intracellular cAMP.

Alleles↗

PubMed1987

Increased free intrasynaptosomal Ca2+ by neurotoxic organometals: distinctive mechanisms.

Effects of several alkylmetals on free intrasynaptosomal Ca2+ concentration, [Ca2+]i, were studied in vitro using the fluorescent Ca2+ indicator fura-2. Neurotoxic alkylmetals methylmercury (Met-Hg), triethyllead (TEL), triethyltin (TET), and trimethyltin (TMT) (at 2.5-30 microM) increased [Ca2+]i to different degrees. Met-Hg was the most potent, elevating [Ca2+]i 100-800 nM, dose dependently and significantly more than high K+ (150 nM) or veratridine (350 nM). The effect of Met-Hg could not be inhibited with a Ca2+ channel blocker, verapamil, nor with a Na+ channel blocker, tetrodotoxin. Inhibition of the mitochondrial Ca2+ uptake in situ with rotenone + oligomycin decreased the potency of Met-Hg to elevate [Ca2+]i but did not change the resting [Ca2+]i. Met-Hg also slightly decreased synaptosomal ATP. TEL and TET elevated [Ca2+]i by 100-200 nM. The effect of TEL, but not that of TET, could be blocked with verapamil (36%) and veratridine (67%). TEL was less efficient in the presence of ouabain. Neither TEL nor TET had significant mitochondrial effects in situ contributing to [Ca2+]i. TMT increased [Ca2+]i less than TET while dimethyltin and methyltin were inactive. These results indicate that neurotoxic derivatives of alkylmetals studied increase [Ca2+]i. This occurs mainly either by nonspecific increase (Met-Hg, TET) of Ca2+ leakage through the plasma membrane and/or specific interference with the mechanisms regulating Ca2+ fluxes through the plasma membrane (TEL).

Adenosine Triphosphate↗

PubMed1990

Mitochondrial modifications in a single nuclear mutant of Saccharomyces cerevisiae affected in cAMP-dependent protein phosphorylation.

This paper reports studies of bioenergetic modifications in a TTR1 single-nuclear mutant, isolated as resistant to triethyltin, an inhibitor of mitochondrial ATPase, and effective in cAMP-dependent protein phosphorylation. This mutant appears to have lost the wild-type cell ability to respond to a decrease of oxygen concentration in the growth medium by a decrease of cytochrome concentration in the cell. ATP synthesis rate in mutant cells in both the prestationary and stationary phase of growth appeared increased in comparison to wild-type cells, as too was respiration rate. A comparative study of mitochondria extracted from wild-type and from TTR1 mutant cells showed an increase in respiration rate, an increase in ATP synthesis rate, and an increase in TPP+ uptake in mutant mitochondria. The specific ATPase activity, as well as its sensitivity to TET, appears to be similar for mitochondria extracted from both strains. It was proposed that the modification of mitochondrial biogenesis in the TTR1 mutant may be due to a response of the cell to an increase in ATP hydrolysis caused by the mutation. It is also possible that the modification in cAMP-dependent protein kinase regulation which appeared to occur in this mutant affects protein(s) involved in mitochondrial biogenesis.

Adenosine Triphosphatases↗

PubMed1988

Chloride-dependent uncoupling of oxidative phosphorylation by triethyllead and triethyltin increases cytosolic free calcium in guinea pig cerebral cortical synaptosomes.

Metabolically competent isolated cerebral cortical nerve terminals were used to determine the effects of triethyllead (TEL) and triethyltin (TET) on cytosolic free calcium ([Ca2+]c), on plasma and mitochondrial membrane potentials, and on oxidative metabolism. In the presence of physiological concentrations of extracellular ions, 20 microM TEL and 20 microM TET increase [Ca2+]c from 185 nM to 390 and 340 nM, respectively. A simultaneous depolarization of plasma membrane potential (delta psi p) by only 3-4 mV occurs, a drop which is insufficient to open the voltage-sensitive Ca2+ channels. In contrast, an instant and substantial depolarization of mitochondrial membrane potential (delta psi m) upon addition of TEL and TET is evident, as monitored with safranine O fluorescence. At the same concentration, TEL and TET stimulate basal respiration of synaptosomes by 45%, induce oxidation of endogenous NAD(P)H, and reduce the terminal ATP/ADP ratio by 45%. Thus, TEL and TET inhibit ATP production of intrasynaptosomal mitochondria by a mechanism consistent with uncoupling of oxidative phosphorylation. This bioenergetic effect by TEL and TET can be prevented by omitting external chloride, and a concomitant reduction of the increase in [Ca2+]c by about 60% is observed. Uncoupling of mitochondrial ATP synthesis from oxidation by TEL and TET, [corrected] a process that is dependent on external chloride, is the main mechanism by which they [corrected] increase [Ca2+]c.

Adenosine Diphosphate↗

PubMed1984

Neurobehavioral toxicity of triethyltin in rats as a function of age at postnatal exposure.

Triethyltin (TET) has been shown to be neurotoxic when injected on postnatal day (PND) 5. In the present experiment we examined the toxicity of a single exposure to TET at several postnatal ages. Rat pups were injected ip with 0 (saline), 1.5, 3.0, or 6.0 mg/kg TET bromide on PND 1, 5, 10 or 15. In agreement with our previous data, PND-5 exposure to 6 mg/kg TET produced behavioral toxicity and decreased adult brain weight. High dose pups were less successful in descending on a rope at 20 and 21 days of age, and were hyperactive in figure-eight mazes at 29-30 and 57-58 days of age. The spatial distribution of activity was also altered: photocell counts were increased primarily in the figure-eight area of the maze. The size of the milk bands was reduced in 6 mg/kg pups injected on either PND 1 or PND 5. Preweaning growth was decreased following all injection ages; this reduction was most pronounced for pups exposed to TET on PND 1 and PND 5. Mating behavior was disrupted in 6 mg/kg males irrespective of age at exposure. These data demonstrate a differential sensitivity to the toxicity of TET during postnatal life, with maximal susceptibility on PND 5.

Age Factors↗

PubMedDate not supplied

Effects of trialkyltins on the schedule-controlled behavior of the pigeon.

Male White Carneaux pigeons trained to respond for food under a multiple fixed-ratio fixed-interval schedule of reinforcement were given single injections of trimethyltin (TMT), or triethyltin (TET). A dose of 0.3 mg/kg TMT produced no effect on behavior, while a 1.0 mg/kg dose was a threshold dose and 1.75 mg/kg produced behavioral changes that persisted for months in some birds. TMT produced effects on responding under the multiple schedule at approximately the same doses that produce neuronal damage in the hippocampus and the brain stem of the pigeon. Higher doses given to untrained birds produced signs of extensive neurological damage. A dose of 1.0 mg/kg of TET decreased rates of responding under both schedule components three hours after administration, but behavior usually had recovered by the next day. Doses of 3.0 and 5.6 mg/kg had similar effects, but responding did not recover for several days. Some birds showed significant rate increases, especially under the fixed-interval component several days to several weeks after TET administration. Doses greater than 10 mg/kg TET were lethal. Dose-effect curves for the effects of d-amphetamine, chlorpromazine and morphine on responding under the multiple schedule were determined for some birds before and one month after 1.0 and 1.5 mg/kg of TMT. TMT shifted the dose-effect curve for d-amphetamine to the right, but it did not produce systematic changes in the dose-effect curves for morphine and chlorpromazine.

Animals↗

PubMed1991

Triorganotin inhibition of rat cardiac adenosine triphosphatases and catecholamine binding.

Triorganotins have been reported to affect heme metabolism as well as the cardiovascular system. Our recent studies indicated that these organotins inhibit cardiac sarcoplasmic reticulum Ca(2+)-transport and cAMP-stimulated phosphorylation of specific proteins involved in Ca2+ transport, suggesting their interference with cardiac adrenergic function. The present study determines the effect of three organotins--tributyltin bromide (TBT), triethyltin bromide (TET) and trimethyltin chloride (TMT)--on rat cardiac ATPases and catecholamine binding, since these phenomena are involved in cardiac function. Cardiac membrane fraction was prepared from heart ventricles of male Sprague-Dawley rats. All three organotins inhibited cardiac Na+,K(+)-ATPase, [3H]ouabain binding, K(+)-activated p-nitrophenyl phosphatase (K(+)-PNPPase) and oligomycin-sensitive (OS) and oligomycin-insensitive (OI) Mg(2+)-ATPase in a concentration-dependent manner. K(+)-PNPPase was less sensitive to these triorganotins when compared to Na+K(+)-ATPase, suggesting that triorganotins affect the Na(+)-pump activity by acting on the Na(+)-dependent phosphorylation process. OS Mg(2+)-ATPase was more sensitive to these organotins when compared to OI Mg(2+)-ATPase, confirming their potent effect on the enzymes of oxidative phosphorylation. The order of potency is TBT greater than TET greater than TMT. TET and TMT, but not TBT, inhibited [3H]norepinephrine and [3H]dopamine binding to cardiac membranes in a concentration-dependent manner, the effect being more with TET. These results suggest that triorganotins inhibit sodium pump activity as well as ATP synthesis. Since Na+,K(+)-ATPase is involved in the active transport of catecholamines, triorganotins not only inhibited the catecholamine transport but also to some extent affected catecholamine binding, thus interfering with cardiac function.

Adenosine Triphosphatases↗