SEARCH · PubMed Health

Results for “Trimethyltin Compounds”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources

PubMed1986

Trimethyltin ototoxicity: evidence for a cochlear site of injury.

The environmental contaminant, trimethyltin (TMT), produces a profound elevation in tone intensity necessary to inhibit the acoustic startle reflex in laboratory animals which recovers over a prolonged period except at very high frequencies. The recovery that is observed does not begin until 3 to 5 weeks after a single acute administration depending upon dosage. As opposed to the very temporary threshold shifts by the salicylates and loop diuretics or the permanent and progressive ototoxicity resulting from aminoglycoside antibiotics the time course for recovery of acoustic startle reflex inhibition after TMT appears to be an anomaly for a chemical ototoxicant. In terms of the duration of loss only, this pattern appears similar to that sometimes observed after noise exposure. The current investigation replicates the finding that recovery of acoustic startle reflex inhibition after TMT is frequency related in that only the highest frequency impairment appears to be permanent. While this frequency dependence suggests a cochlear locus of injury, both the known neurotoxic effects of TMT and the time course of the behavioral impairment suggest a more central locus of injury. Compound action potential and cochlear microphonic recordings made from the round window in the current study confirm a preferential high frequency effect of TMT and demonstrate a significant cochlear component to the ototoxic effects of this agent.

Action Potentials↗

PubMedDate not supplied

Trimethyltin reduces recurrent inhibition in rats.

Rats with electrodes chronically implanted in the perforant path for electrical stimulation, and dentate gyrus for recording were treated with a single oral administration of either saline, 5 mg/kg trimethyltin (TMT) or 6 mg/kg TMT. Recurrent inhibition was assessed by paired pulse activation of the perforant path input to the dentate gyrus. The measure of recurrent inhibition employed was the ratio of the population spike amplitudes of the responses to the first and second of the paired stimuli. Inhibition was assessed immediately before, and at 2, 24 and 120 hr following TMT. The results indicated a reduction in inhibition as early as 2 hr following treatment, suggesting that TMT-induced destruction of hippocampal pyramidal cells may be secondary to their over-activation from an uninhibited mossy fiber system.

Analysis of Variance↗

PubMed1986

Trimethyltin exposure produces an unusual form of toxic auditory damage in rats.

A single injection of trimethyltin chloride (TMT; 2, 4, or 6 mg/kg) is shown to produce a frequency-specific, dose-dependent auditory impairment, as well as to decrease the amplitude of the acoustically elicited startle response, in exposed rats. This finding stands in contrast to data presented earlier on the effects of triethyltin bromide (TET), which produces changes in startle response without affecting auditory acuity. Animals intoxicated with TMT at moderate doses appear to recover their auditory acuity over the course of several weeks. This slow recovery of auditory function, which is uncharacteristic for chemical ototoxicity, suggests that TMT may be a useful model agent for studying ototoxic mechanisms.

Acoustic Stimulation↗

PubMed1982

Effect of trimethyltin on chemically-induced seizures.

The effect of trimethyltin (TMT; 4.26 mg/kg i.p.), at 1 and 14 h following administration, on chemically-induced seizures in mice is reported. At 1 h following administration, TMT decreased seizure responsiveness and protected animals from bicuculline, isonicotinic acid hydrazide (INH) and pentylenetetrazol (PTZ) induced seizures. At 14 h following administration, TMT provided little protection against bicuculline, INH or PTZ induced seizures. Only slight decreases in seizure responsiveness were observed with strychnine induced seizures at either 1 or 14 h. By 16 h following administration, animals exhibited spontaneous tremors and convulsions. The results indicate that TMT exerts a biphasic effect on central nervous system excitability.

Animals↗

PubMedDate not supplied

Effects of delay, intertrial interval, delay behavior and trimethyltin on spatial delayed response in rats.

Working memory was modeled in rats using a delayed response task with spatial location as the discriminative cue. Rats received food for pressing 1 of 2 retractable levers in the choice phase of a trial if that lever had been presented in the prior sample phase of that trial. When delays of 0-20 sec were imposed between sample and choice, choice accuracy declined with increasing delay. With short intertrial intervals (ITIs), choice accuracy decreased more at long delays than at short delays, showing that interference from previous trials impaired memory but not discrimination. Rats emitted overt mediating responses during delay by pressing the levers in the retracted position. However, the frequency of delay presses was low (less than 2/trial in all rats) and neither their frequency nor accuracy was related to choice accuracy. Resetting the delay interval for each delay press did not significantly alter choice response accuracy. Trimethyltin (TMT), 7 mg/kg IV, reduced the choice accuracy of one rat to chance levels at all delays; two other rats were affected transiently. TMT reduced choice accuracy during weeks 1 and 4 postinjection, with significant effects on the linear slope and intercept of the mean retention gradient during week 4. TMT did not affect responses to the retracted levers during delays. TMT treatment also elevated levels of glial fibrillary acidic protein (GFAP) in the CNS, measured 4 weeks after treatment. Hippocampal GFAP correlated highly with the reduction in choice accuracy during week 1 (r = -.903) and week 4 (r = -.797) postTMT.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Effects of trimethyltin chloride on the LiCl dose-response function for conditioned taste aversions in rats.

Twenty-one days following intragastric administration of 6.0 mg/kg of TMT (TMT chloride base/kg) or equivolume distilled water, groups of rats were injected with various doses of LiCl (0, 0.15, 0.60 or 1.8 mEq/kg) following the consumption of a novel saccharin solution. Both groups subsequently avoided the consumption of saccharin, with the degree of the aversion directly related to the dose of LiCl. Further, there was no difference between the TMT- and non-TMT-treated rats in the degree of aversion at any dose. These data suggest that the previously-reported effect of TMT on long-delay taste aversion learning was not likely due to changes in sensory responsiveness.

Animals↗

PubMedDate not supplied

Effects of trimethyltin chloride on differential-reinforcement-of-low-rate responding.

The effects of a range of doses of trimethyltin chloride (1.8-7.0 mg/kg, TMT) on responding maintained under a differential-reinforcement-of-low-rate 15-sec schedule of water presentation were examined in rats. TMT produced a large decrease in the percent of reinforced responses and consequently a decrease in the rate of reinforcement. These effects were due primarily to prolonged bursts of nonreinforced responses. In contrast to the gradual dose-related decrease in body weight produced by TMT, responding was disrupted only at the highest dose tested, i.e., 7.0 mg/kg. The results were discussed in terms of the neurotoxic effects of TMT on the limbic system.

Animals↗

PubMed1989

Effects of adrenalectomy and corticosterone on hippocampal lesions induced by trimethyltin.

The effects of adrenalectomy and corticosterone supplementation on the neurotoxicity of trimethyltin (TMT) were tested. CD-1 mice with or without adrenalectomy were injected with TMT at a dose of 3.0 mg/kg body wt. At 48 h post-TMT administration, the animals were killed for pathological examination. It was found that the adrenalectomized animals developed even more severe lesions in the hippocampal formation (fascia dentata granule cells) than the intact animals. When animals were given a supplement of corticosterone pellets at doses of 0.15, 1.5, and 7.5 mg, there was a reduction of lesion development. Total alleviation of pathology was seen at the two higher doses of supplementation. Our present investigation strongly indicates that there may be a close and important interrelationship between TMT-induced neurotoxicity and adrenal function.

Adrenalectomy↗

PubMedDate not supplied

Chronic neonatal organotin exposure alters radial-arm maze performance in adult rats.

Long-Evans rats were intubated with 0.3 or 1.0 mg/kg of triethyltin sulfate (TET) or 0.3 mg/kg of trimethyltin hydroxide (TMT) from postnatal day 3-29. 1.0 mg/kg of TMT was given on alternate days beginning on postnatal day 3. Learning and memory were assessed in an automated radial-arm maze when the rats were 180-200 days old. With this maze accuracy and activity data can be collected simultaneously. TET or TMT treatment resulted in an increase in the number of days required to adequately perform and radial-arm maze task, and a transient deficit in accuracy. However, the most pronounced effect in both TET and TMT-treated animals was hyperactivity which became manifest on the second day of testing and persisted throughout the remainder of testing.

Analysis of Variance↗

PubMedDate not supplied

Increased seizure susceptibility following trimethyltin administration in rats.

Acute treatment with trimethyltin (TMT) produces a multitude of behavioral effects including spontaneous convulsions in some animals. The present study used several different experimental seizure models to investigate seizure susceptibility in TMT-treated rats. Rats surgically implanted with electrodes in the amygdala and treated with TMT kindled more rapidly than saline-treated controls. Similarly, rats implanted with electrodes in the dorsal hippocampus kindled more rapidly than controls. Although TMT did not alter the properties of hippocampal afterdischarges, the threshold for production of after discharges was increased in both hippocampal and amygdaloid kindled rats, probably due to cell loss. TMT also increased the sensitivity of rats to pentylenetetrazol, thus suggesting that the increased seizure susceptibility was not limited to the limbic system.

Animals↗

PubMedDate not supplied

Visual system dysfunction following acute trimethyltin exposure in rats.

Trimethyltin (TMT) has been shown to produce damage in the limbic system and several other brain areas. To date, damage to sensory systems has not been reported. The present study investigated the integrity of the visual system following acute exposure to TMT. Rats were chronically implanted with electrodes for recording the evoked response from either the visual cortex or optic tract following photic stimulation. Following recovery, the animals were exposed to either 0 (saline), 4, 5, 6, or 7 mg/kg trimethyltin chloride (TMT). Evoked potentials were averaged the peak-to-peak amplitudes and latencies were determined. The results indicated that exposure to TMT produced alterations in the visual evoked response. The pattern of changes suggested two effects, an alteration in retinal processing and an alteration in arousal. The manifestation of these changes was an increase in early peak latencies recorded from the visual cortex and the optic tract, a decreased amplitude recorded from the visual cortex and optic tract early peaks (all suggestive of retinal changes) and a decreased P3N3 amplitude and N3 latency recorded from the visual cortex (suggestive of increased arousal). The results demonstrate that TMT does produce alterations in sensory systems as well as in the limbic system.

Analysis of Variance↗

PubMed1989

Effects of captopril on locomotor activity, passive avoidance behaviour and spatial memory tasks in the trimethyltin-treated rat.

The potential neuroprotective/cognitive enhancing actions of captopril were investigated in the trimethyltin (TMT)-induced neurotoxicity rat model. Acute exposure to TMT produces alterations in locomotor activity, passive avoidance behaviour and spatial memory tasks. Captopril treatment given in combination with the single acute injection of TMT reversed the deficits in spatial memory tasks in 8 out of 25 trials. While post-treatment of TMT-treated rats with captopril brought about a significant improvement in 3 out of 25 trials, pre-treatment of rats for 3 weeks with captopril did not reverse the behavioural deficits produced by TMT in the Morris maze test. Captopril treatment did not block the characteristic hyperactivity or the deficits in passive avoidance behaviour of TMT-treated animals.

Animals↗

PubMed1982

Trimethyltin inhibits uptake of neurotransmitters into mouse forebrain synaptosomes.

Trimethyltin (TMT), in a concentration dependent manner, inhibits in vitro uptake of gamma-aminobutyric acid (GABA), norepinephrine and serotonin by mouse forebrain synaptosomes with IC50S of 75, 43 and 24 microM, respectively. At 2 h and 14 h following in vivo administration of TMT (4.26 mg/kg; i.p.) to mice, GABA and serotonin uptake by forebrain synaptosomes are decreased, although norepinephrine uptake was not significantly affected. In vitro kinetic analyses of TMT inhibition of forebrain synaptosomal uptake of GABA, norepinephrine and serotonin indicated that the inhibition was not of the competitive type. This inhibition of uptake of neurotransmitters could be responsible, at least in part, for altered neurotransmitter levels in the synaptic cleft and may contribute to altered nervous system function during TMT intoxication.

Animals↗

PubMedDate not supplied

The trimethyltin syndrome in rats.

Trimethyltin (TMT) chloride, administered to adult male Long-Evans hooded rats, produced a unique and distinctive behavioral syndrome consisting of spontaneous seizures, tail mutilation, vocalization and hyperreactivity. The LD50 for TMT was weight dependent; in large rats (e.g., 450 g), 7 mg/kg TMT produced significant weight loss and lethality, whereas in small rats (e.g., 250 g), 7 mg/kg produced neither weight loss nor lethality. TMT produced mild hypothermia and tremors. Results are discussed in comparison with kainic acid-induced morphological alterations and septal lesion-induced behavioral alterations. Histopathological evaluations of hippocampal tissue revealed cell loss that was largely confined to regio inferior pyramidal cells. TMT offers potential as a tool for investigations of limbic system structure and function.

Animals↗

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↗

PubMed1986

On the role of seizure activity in the hippocampal damage produced by trimethyltin.

Trimethyltin (TMT) causes a pattern of hippocampal damage in rats that is similar to that caused by convulsant chemicals or seen in the brains of some human epileptics. Therefore, we investigated the possible role that TMT-induced seizure activity might play in the hippocampal damage produced by this organotin. The morphologic effects of systemically administered TMT were compared to those of kainic acid given by the same route. Unlike kainate, TMT produced seizures in only a subset of treated animals and with a latency of days rather than minutes. Evaluation of morphology during the acute seizure period revealed that TMT-induced seizures were associated with a variable pattern of granule and pyramidal cell necrosis and acute dendritic swelling in the two associational/commissural hippocampal pathways, one from CA3 to CA1-CA3 and the other from the hilus to the proximal dendrites of dentate granule cells. The TMT-induced damage contrasted sharply with the acute pattern of kainate-induced damage that consisted of acute dendritic swellings in the distal granule cell dendrites, hilus and mossy fiber region. TMT-treated rats that did not exhibit seizures in the one week after injection exhibited minimal pathology during this period. These results suggest that at least part of the damage to granule and pyramidal cells produced by TMT is mediated by the seizure activity produced by this compound. Although the resulting lesions to the CA1-CA3 pyramidal cells may appear similar in both TMT- and kainate-treated rats long after injection, evaluation of acute pathology during the active seizure phase indicates that these compounds induce seizure activity in different hippocampal pathways and cause different patterns of irreversible neuronal damage as a result.

Animals↗

PubMedDate not supplied

Neuropathology of mouse hippocampus in acute trimethyltin intoxication.

BALB/c mice were injected IP with a single dose of trimethyltin chloride (3.0 mg TMT/kg body weight). Severe body tremor was observed within 12 hours post-injection. All animals were sacrificed 48 hours post-injection by means of intracardial perfusion with 2.5% buffered glutaraldehyde. Light microscopic examination revealed extensive neuronal necrosis in the granule cells of the fascia dentata of the hippocampus. Scattered neuronal loss was also observed in the pyriform cortex, the neocortex, amygdaloid nucleus, and the brainstem. Electron microscopic examination of the hippocampus revealed lysosomal accumulation in both the granule cells and pyramidal neurons. While extensive cellular necrosis was observed in the granule cells, the pyramidal neurons only displayed some dilatation and vacuolation of their endoplasmic reticulum. This report represents the first in depth pathological study in the mouse hippocampus following an acute exposure to TMT.

Animals↗

PubMedDate not supplied

Increased forebrain beta-adrenergic ligand binding induced by trimethyltin.

Systemic injection of the organometal neurotoxin trimethyltin (TMT) into rats causes impairments in learning and memory. However, there is a discontinuity in dose-response functions, such that the deficit which emerges with a higher, acutely toxic dose, is qualitatively different from the impairment induced after lower doses. To investigate synaptic receptor changes associated with behavioral deficits, neurotransmitter-receptor ligand binding assays were done in forebrain areas of rats given TMT (3.6 or 7.5 mg/kg). Binding of the beta-adrenergic ligand, dihydroalprenolol in frontal cortex and amygdala/pyriform cortex was an inverted U-shaped function of TMT dose, with rats given the median dose exhibiting increased binding. The curvilinear dose-response functions in behavioral and biochemical assays suggest that altered forebrain noradrenergic neurotransmission could play a role in behavioral deficits.

Animals↗