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Results for “Trimethyltin Compounds”

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At least 127 records · Page 7Linked to original sources

PubMed1990

Frequency of micronuclei induced in peripheral lymphocytes by trimethyltin chloride.

The clastogenicity of trimethyltin chloride was evaluated in human peripheral blood lymphocytes with micronucleus counts (MNC) as the endpoint. Two concentrations (0.5 micrograms and 1.0 microgram) of trimethyltin chloride were added to lymphocytes of healthy male and female subjects of different age groups, in mitogen-stimulated and serum-supplemented culture medium (RPMI 1640, Gibco) for 48 h at 37 degrees C. A significant increase in micronucleus counts was observed with both doses, which was more pronounced with the lower dose. ANOVA in male and female donors revealed significant differences between age groups (P less than 0.001), chemical concentrations (P less than 0.001) and for the interaction of these 2 factors (P less than 0.05 in females only). However, no regular increase or decrease in MNC frequencies was observed with the donor's age. Higher frequencies of MNC enhancement were observed in male individuals than in females.

Adolescent↗

PubMedDate not supplied

Effects of trimethyltin on incremental repeated acquisition (learning) in the rat.

The effects of the neurotoxicant, trimethyltin (TMT), on the acquisition of serial position response chains (learning) in adult rats were examined. Animals performing incremental repeated acquisition tasks for food were injected once with either 7.5 or 8.7 mg/kg TMT, IP. TMT decreased efficiencies (correct/total responses) in all 5 subjects; maximal decrements occurred 1-3 weeks post-treatment. Efficiency in 3 rats returned to pre-TMT levels within 5 weeks; values for the other 2 animals did not return in 3 months. Errors were markedly increased 1-2 weeks post-treatment in 4/5 subjects. Response rates increased for 2 animals within a week of TMT treatment and remained elevated for 5 weeks. Sustained rate increases occurred for 2 other animals 4-5 weeks after treatment. Thus, TMT effects on various aspects of incremental repeated acquisition behavior follow different time-courses.

Animals↗

PubMed1984

Neuropathology of trimethyltin intoxication. IV. Changes in the spinal cord.

Young C57BL/6N mice were injected (ip) with trimethyltin chloride at a dosage of 3.0 mg/kg body wt. Animals were sacrificed between 48 to 72 hr postinjection by means of intracardial perfusion of saline solution followed by 2.5% buffered glutaraldehyde. For light microscopy, the cords were further fixed in 10% buffered formalin and embedded in Paraplast. For electron microscopy, tissue samples were obtained from the cord levels at L1-L4, further fixed in glutaraldehyde and osmium tetroxide, and embedded in Epon. Chromatolytic and vacuolar changes involving neurons mainly in the medial and lateral motor nuclei of the anterior horns were observed. Electron microscopy revealed lysosomal accumulation and extensive dilatation of the cytoplasmic membrane systems (endoplasmic reticulum, Golgi complex). Large intraneuronal vacuoles were formed as a result of extensive intraneuronal edema. Progressive distention of the cytoplasmic membranes resulted in severe vacuolation, disintegration, and total breakdown of the neurons.

Animals↗

PubMed1982

Acute treatment with trimethyltin alters alcohol self-selection.

Male rats of the Long-Evans strain were divided into two equal groups of nine each and given either 7.0 mg/kg trimethyltin (TMT) or 0.9% saline by intragastric gavage. The pattern of self-selection of alcohol in concentrations of 3%--30% was examined in both groups at 21 and 150 days following the gavage. The TMT-treated rat consistently drank less alcohol than did the controls at every concentration of alcohol. This difference in alcohol intake was equally significant when the rats were tested in a food-contingent, schedule-induced polydipsia situation. Further, although the TMT-lesioned animal consumed fewer calories per day in the form of alcohol, their overall daily caloric intakes were slightly higher than those of the controls. These results are interpreted as a consequence of damage to structures of the forebrain and as part of a syndrome of behavioral and neurological pathology.

Alcohol Drinking↗

PubMed1984

Alterations in regulatory and locomotor behaviors following trimethyltin exposure in the rat: a time and dose analysis.

Adult male hooded rats were tested pretreatment for spontaneous alternation and open-field behaviors. Animals were then intubated with either 5 or 7 mg/kg trimethyltin chloride (TMT Cl) or the isotonic saline vehicle. Post-treatment, animals were again tested for spontaneous alternation and open-field behaviors during three separate 5-day periods: days 14-18, days 56-60 and days 106-110. Additionally, both body weight and water intake were assessed. The larger dose of TMT Cl resulted in significant, but temporary reduction in body weight, elevated water intake for approximately 3 weeks, and a persistent increase in open-field activity. The smaller dose of TMT Cl resulted in elevated water intake for approximately 3 weeks and a temporary increase in open-field activity. Since the tendency to enter choice arms decreased in all groups across testing sessions, the effects of TMT Cl on spontaneous alternation could not be accurately assessed.

Animals↗

PubMed1988

Grafts containing fetal hippocampal tissue reduce activity and improve passive avoidance in hippocampectomized or trimethyltin-exposed rats.

Embryonic Day 16 or 17 rat tissue containing either hippocampus with some medial pallial anlage or cerebellar/alar plate anlage was transplanted to the site of the ablated hippocampus of otherwise normal adult rats or adult rats previously exposed to the neurotoxin trimethyltin. Ninety to one hundred five days later these rats were compared to control rats in acquisition of passive avoidance and in open field activity. Transplantation of both types of tissue produced behavioral recovery on both tasks in rats with hippocampal lesions that had not been exposed to trimethyltin. Only hippocampal transplants produced recovery of function in rats given trimethyltin. Although transplants of hippocampal tissue had an organotypic structure that was easily differentiated with cell and fiber stains from that of the cerebellar transplants, neither of these routine histological procedures nor immunocytochemical analysis revealed differences between transplants made into normal rats or toxicant-exposed rats. Either of two mechanisms may account for the ability of the transplants to produce behavioral recovery. These are reconstruction of damaged circuitry by the transplant and neurotrophic action of the developing transplant on the host brain. The second mechanism alone may be sufficient to restore function in brain-lesioned but otherwise normal rats. Therefore, either type of transplant is effective. Both mechanisms may be necessary for recovery in brain-lesioned, toxicant-exposed rats. Therefore, only transplants of tissue homotypic to the tissue removed from the brain are effective.

Animals↗

PubMedDate not supplied

Trimethyltin-induced hyperactivity: time course and pattern.

Adult male Long-Evans rats were intubated with either 0, 5, 6 or 7 mg/kg trimethyltin chloride. Activity was measured for 1 hr in a figure-eight maze 2 hr after dosing (day 0) and again on days 4, 8, 16 and 32 after dosing. On days 49-51, activity was measured in a figure-eight maze over a 23-hr period. There were no differences in activity on the day of dosing, but on all subsequent test days the 7 mg/kg TMT animals were hyperactive. TMT also altered the spatial pattern of activity: activity was increased in the "figure-eight" portion of the maze but not in the blind alleys. ACtivity of the 7 mg/kg TMT animals was increased during all periods in the 23-hr test. Decreases in the length of the pyramidal cell line (CA1 to CA3c of the hippocampus) confirmed neuronal cell loss in TMT-dosed rats.

Animals↗

PubMed1989

Cytotoxic effects of trimethyltin chloride on human peripheral blood lymphocytes in vitro.

Trimethyltin chloride was found to induce cytotoxic damage in vitro in human peripheral blood lymphocytes. Two concentrations (0.5 micrograms and 1.0 micrograms) were added to lymphocytes from male and female subjects in mitogen stimulated and serum supplemented culture medium for 72 h. A dose-related increase of inhibition of replication index (P less than 0.01) and cell division (P less than 0.001) was observed. The frequencies of abnormal cells and chromosomal aberrations such as chromatid and chromosome breaks, dicentrics, triradial and quadriradial configurations were increased significantly (P less than 0.001), as were micronucleus counts (P less than 0.001) and sister chromatid exchanges (P less than 0.001). Endoreduplication, an extremely rare spontaneous event in human lymphocytes, was observed in a few cases at all dose levels. The effects were more pronounced in lymphocytes obtained from habitual smokers.

Cell Cycle↗

PubMed1984

Trimethyltin retinopathy. Relationship of subcellular response to neuronal subspecialization.

Retinal neurons from rats acutely intoxicated with trimethyltin (TMT) were examined by light and electron microscopy to determine if there is a relationship between the subcellular response of a neuron to TMT and its morphologic subspecialization. Subcellular pathologic alterations were present in neurons from all three cellular layers of the sensory retina. However, the type and degree of subcellular response varied among the highly subspecialized neurons of the different retinal layers. Clusters of dense-cored vesicles and tubules were mainly limited to neurons of the ganglion-cell layer, large accumulations of dense bodies were mainly limited to neurons of the inner nuclear layer, and neuronal necrosis was mainly limited to the photoreceptor cells. The inner segment of the photoreceptor cell shared with the perikaryon of more conventional neurons a special vulnerability to TMT cytotoxicity. Our results suggest that the morphologic subspecialization of neurons affects the type and the degree of subcellular response to TMT.

Animals↗

PubMedDate not supplied

Somatosensory dysfunction following acute trimethyltin exposure.

A variety of trimethyltin (TMT)-produced sensory and behavioral dysfunctions have been reported. In this study the functional integrity of the somatosensory system was evaluated. Animals were tested using three different measures prior to (day 0) and 1, 4, and 16 days following dosing with either 0 (saline) or 7 mg/kg TMT. The tests employed were: (1) hot-plate pain threshold: (2) dorsal caudal nerve response threshold and conduction velocity; and (3) the somatosensory evoked response (SER). In the hot-plate test, TMT treated animals took longer to lick the hind paws in response to the heat. No effects were seen in the nerve function evaluation (conduction velocity and threshold), although increased N1, P1, and P2 latencies and decreased N1P1 amplitude were seen in SER recordings. The fact that no peripheral nerve function effects were observed suggests that the hot-plate and SER findings were the result of central nervous system dysfunction.

Animals↗

PubMedDate not supplied

Trimethyltin-induced changes in gross morphology of the hippocampus.

Acute exposure to trimethyltin (TMT) produces alterations in hippocampal morphology. The purpose of this study was to arrive at a simple method for quantitative assessment of the gross changes in morphology which could then be used as a correlate in studies of TMT toxicity. Adult Long-Evans male hooded rats were treated with a single dose of TMT chloride and sacrificed either (a) within 11 days; (b) following 30 days; or (c) 105 days following treatment. Among a variety of morphological measures explored, the easiest and most clearly dosage-related was length of the line of pyramidal cells, from CA1 through CA3c. TMT shortened this line in a dosage- and time-dependent manner. Loss of cells appeared to begin in CA3c and progress through CA3b and CA3a as a dosage and time since treatment increased. It was concluded that this measurement may provide a useful morphological correlate for physiological and behavioral studies of TMT toxicity.

Animals↗

PubMed1984

Trimethyltin disrupts acoustic startle responding in adult rats.

Trimethyltin (TMT) is a limbic-system toxicant which also produces sensory dysfunction in adult animals. In the present experiment, we examined the effects of TMT on the acoustic startle response. Adult male, Long-Evans rats (N = 12/dose) received a single i.p. injection of either 0, 4.0, 5.0 or 6.0 mg/kg TMT hydroxide as the base. The number of responses, latency and peak amplitude of the startle response to a 13 kHz, 120 dB tone were measured 2 h, 2 weeks, and 4 weeks after dosing. For each test session, 10 stimuli were presented at each of three background noise levels (50, 65 and 80 dB). By 2 h after dosing, the number of responses and response amplitude were decreased following 4.0-6.0 mg/kg TMT; these treatment effects persisted through 4 weeks after dosing. Increases in latency were also seen following all dosages of TMT. These data suggest that TMT produces disruption of function within the acoustic-startle pathway.

Acoustic Stimulation↗

PubMed1979

Organotin-mediated exchange diffusion of anions in human red cells.

Organotin cations (R3Sn+) form electrically neutral ion pairs with monovalent anions. It is demonstrated that the tin derivatives induce exchange diffusion of chloride in red cells and resealed ghosts, without any detectable increase of membrane permeability to net movements of chloride ions. The obligatory anion exchange is believed to be due to the permeation of electroneural ion pairs, whereas the organic cation (R3Sn+) has an extremely low membrane permeability. Exchange fluxes of chloride increased with the lipophilicity of the substituting group (R3). At the same molar concentration of organotin, the relative potencies of the tin derivatives as anion carriers (with trimethyltin as a reference) were: methyl 1, ethyl 30, propyl = phenyl 1,00, and butyl 10,000. Tributyltin-mediated anion exchange was studied in detail. The organotin-induced anion transport increased through the sequence: F- less than Cl- less than Br- less than I- = SCN- less than OH-. Partitioning of tributyltin into red cell membranes was greater in iodide than in chloride media (partition coefficients 6.6 and 1.7 x 10(-3) cm, respectively). Bicarbonate, fluoride, nitrate, phosphate, and sulphate did not exchange with chloride in the presence of tributyltin. Chloride exchange fluxes increased linearly with tributylin concentrations up to 10(-5) M, and with chloride concentrations up to at least 0.9 M. The apparent turnover number for tributyltin-mediated chloride exchange increased from 15 to 1,350 s-1 between 0 and 38 degrees C. These figures are minimum turnover numbers, because it is not known what fraction of the organotin in the membrane exists as chloride ion pairs.

Adsorption↗

PubMedDate not supplied

Effects of trimethyltin on evoked potentials in mouse hippocampal slices.

The effects of trimethyltin (TMT) on responses to orthodromic stimulation in the CA1 pyramidal cell layer and dentate gyrus were investigated in mouse hippocampal slices. In both regions exposure to 10.0 microM TMT produced an 80 to 90% reduction in population spike amplitude. Smaller decreases in spike amplitude occurred after 5 microM TMT and these effects were reversible in the pyramidial cell layer. The latency of 5.0 microM effects was longer in the dentate gyrus and were preceded by a slight (20%) increase in spike amplitude. The smallest dose of TMT tested (1.0 microM) did not change response amplitude, but did increase the occurrence of multiple population spike potentials. When TMT was applied during paired-pulse stimulation of the perforant path the potentiation of the second response was not selectively reduced. The results indicate that orthodromic excitability of both pyramidal and granule cells in the mouse hippocampus is decreased by TMT with small differences occurring in latency and reversibility at certain doses.

Animals↗

PubMedDate not supplied

Exposure to trimethyltin significantly enhances acetylcholinesterase staining in the rat dentate gyrus.

Trimethyltin (TMT) is known to produce substantial damage to the hippocampal formation. It also destroys neurons within the entorhinal cortex, thereby causing degeneration of perforant path afferents that terminate in the outer molecular layer (OML) of the dentate gyrus. Surgical destruction of the entorhinal cortex also causes the perforant path to degenerate. This leads to reactive synaptogenesis (axonal sprouting) of septal afferents to the dentate gyrus. The purpose of the present study was to determine whether administration of 6 mg/kg of TMT by gavage to rats would cause axonal sprouting within the septo-dentate projection. A histochemical stain for acetylcholinesterase (AChE) was used. Compared to control subjects rats given TMT exhibited significantly denser AChE staining in the dentate OML. This is putative indication of reactive synaptogenesis within the cholinergic projection to this layer of the dentate and is somewhat surprising because other neurotoxins, such as lead and ethanol, that affect neurons within the hippocampal formation reduce the capacity for reactive synaptogenesis in response to lesions of the entorhinal cortex.

Acetylcholinesterase↗

PubMed1983

Developmental effects of trimethyltin intoxication in the neonatal mouse. I. Light microscopic studies.

The effects of trimethyltin (TMT) intoxication on the developing mouse brain were studied. BALB/c mice were injected intraperitoneally with 3.0 mg TMT/kg body weight on postnatal day 3. Animals were sacrificed at selected intervals to 30 days of age and their brains examined by light microscopy. Increased eosinophilia and granularity of hippocampal pyramidal neurons and neurons of the pyriform cortex were detected as early as 16 hours post-administration. Extensive degenerative and necrotic charges were observed 1 to 10 days post-administration, particularly in hippocampal region CA-3 of Ammon's horn. Cerebellar Purkinje and granule neurons, basal ganglia and cerebral cortex were involved to a lesser extent. Pathological changes of granule cells in the fascia dentata were much less extensive than reported in adult mice. Astrogliosis was occasionally pronounced. Distribution of lesions within the hippocampus indicate that acute neonatal TMT exposure results in a different regional pattern of injury than in acutely treated adult mice.

Animals↗

PubMed1984

Effects of acute trimethyltin exposure on appetitive acquisition and extinction performance in the adult rat.

Adult male rats were given one intragastric infusion of either 7 mg/kg trimethyltin chloride (dose calculated as the base of trimethyltin [TMT]) or physiological saline. Twenty-one days after dosing, subjects from each condition were divided into two equal-sized groups and trained with either partial (PRF) or continuous (CRF) reinforcement in a straight alley maze. The acquisition phase of training, lasting 40 trials (4 trials/day), was followed by 20 trials of extinction training (4 trials/day). Analyses performed on total speed revealed that TMT-treated subjects performed at lower levels during acquisition than controls regardless of schedule condition. Also, the rate of resistance to extinction was significantly reduced for treated subjects compared with that of controls regardless of the training schedules used during acquisition. A partial reinforcement extinction effect was observed for both control and TMT-treated subjects, that is, independent of dose regimen; PRF training occasioned greater persistence during extinction than did CRF training. These findings are discussed in terms of their implications for contemporary empirical and theoretical issues relating to TMT-induced hippocampal lesions.

Animals↗

PubMedDate not supplied

Disruption of learned and spontaneous alternation in the rat by trimethyltin: chronic effects.

Trimethyltin (TMT) is a known neurotoxin which produces behavioral anomalies including hyperactivity, aggressiveness, perseveration, and learning deficits. These dysfunctions appear to be related to a severe loss of neurons in the hippocampal formation of the TMT-treated rat. In order to assess the effect of TMT exposure upon spontaneous and learned alternation, male Long-Evans rats were pretested for reinforced spontaneous alternation and then treated with either 7 mg/kg of TMT [( CH3]3SnCl) or the 0.9% NaCl vehicle. After treatment these groups were further subdivided and half of each group was tested in a "T" maze for reinforced spontaneous alternation while the remainder was tested for learned alternation. The TMT-treated rats uniformly ran faster on the second choice of reinforced spontaneous alternation tests than did controls. In addition, the TMT-treated rats made fewer alternations than controls, regardless of whether or not only successful alternations were being reinforced. These results are discussed in light of the known neurobehavioral consequences of TMT exposure.

Animals↗