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PubMed1983

Inhibitory effect of triethyltin on taurine transport by glioma cells.

The effects of triethyltin (TET) on the transport of taurine, glutamate, lysine, Na+, K+ (using 86Rb+ as tracer), and Cl- by LRM55 glioma cells were examined. Taurine transport was inhibited by TET at much lower concentrations (IC50 = 2.5 microM) than either glutamate or lysine transport (135 and 110 microM, respectively). TET had no significant effect on Na+, Cl-, or 86Rb+ influx at the low concentrations greater than 100 microM. The failure of low concentrations (less than or equal to 10 microM) of TET to affect ion transport indicated that inhibition of taurine transport was not secondary to effects of TET on ion movements or gradients. This conclusion was supported by the observation that neither ouabain nor furosemide, which do affect ion movement and gradients, strongly inhibited taurine transport. Uncouplers and inhibitors of oxidative phosphorylation (cyanide, 2,4-dinitrophenol, and carbonyl cyanide-m-chlorophenyl hydrazone) also had only small effects on taurine transport, suggesting that inhibition by TET was not secondary to possible effects on oxidative phosphorylation. TET had no effect on the efflux of taurine from LRM55 cells at the low concentrations that inhibit uptake, but it induced a nonspecific increase in membrane permeability at much higher concentrations (greater than 100 microM). Tri-n-propyltin and tri-n-butyltin were also potent inhibitors of taurine transport (IC50 = 2.3 and 11 microM, respectively), but trimethyltin was much less potent (144 microM).

Biological Transport↗
PubMed1985

The effects of triethyltin and trimethyltin in rats responding under a DRL schedule of reinforcement.

Rats were trained to respond under a schedule of reinforcement in which only those responses separated by a 10-to 14-sec period of no responding produced a feed pellet (DRL 10 to 14 sec). Each rat received a single dose of trimethyltin (TMT) (5.6, 7.5, or 10 mg/kg) or triethyltin (TET) 1, 3, 4.25, or 5.6 mg/kg). The lowest dose of TMT (5.6 mg/kg) and the lowest dose of TET (1 mg/kg) were without significant effect. At 7.5 mg/kg and 10 mg/kg TMT, the percentage of the total responses spaced 10 to 14 sec apart decreased over the first 8 to 12 days after TMT. Those rats receiving 7.5 mg/kg TMT gradually returned to control values over the next 2 to 3 weeks while those rats receiving 10 mg/kg never recovered. Rats receiving 3, 4.25, and 5.6 mg/kg TET showed a decrease in the percentage of reinforced responses immediately after receiving TET. The behavior of those rats receiving 3 mg/kg returned to control values in 24 hr. Following 4.25 mg/kg TET, the health of the rats deteriorated rapidly. They were kept alive through heroic measures, but then were killed after testing on the 12th day following TET due to their failing health. At 5.6 mg/kg, the rats were killed on the 4th day due to failing health. These results indicate that TMT and TET differ with respect to potency and time course. The behavioral deficits produced by TET parallel the time course of general toxicity while the behavioral effects of acute TMT administration can persist in time long after the general appearance of the rats has returned to normal.

Animals↗
PubMedDate not supplied

Effect of triethyltin chloride on the central aminergic neurotransmitters and their metabolites: relationship with pathophysiology of aging.

Triethyltin (TET) salt intoxication provokes a myelinic vacuolisation associated with a white matter cerebral edema. The central nervous system disturbances accompanying these phenomena (Na-K-ATPase activity, neurological symptoms, water and sodium cerebral content) can be counteracted by drugs used in age-related brain failure; consequently, TET intoxication could be suggested as an experimental model for studying the aging process. The aim of the present study is to follow-up the biogenic amine concentrations in different brain areas of TET treated rats, knowing that modifications of cerebral amines exist throughout the aging process. The following results are obtained: the cerebral water content of the TET treated rats is significantly increased, confirming the existence of a brain edema. Monoamine concentrations are significantly decreased, specifically noradrenaline (in hypothalamus, mesencephalon, cerebellum); serotonin (in striatum, hypothalamus, mesencephalon); dopamine only in hypothalamus; these are accompanied by an increase of the metabolites 5 HIAA (in striatum and mesencephalon) and HVA (striatum). These modifications are compared to those occurring in physiological aging, and hypothetical mechanisms are reviewed. We conclude that TET intoxication must not be considered as a pathophysiological model of brain aging, but may be considered as a useful pharmacological tool for studying experimental drugs liable to counteract brain age-induced disturbances.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1979

The interactions of triethyltin with rat glutathione-S-transferases A, B and C. Enzyme-inhibition and equilibrium-dialysis studies.

Purified glutathione(GSH)-S-transferases A, B and C from rat liver are inhibited by triethyltin (SnEt3). With 1-chloro-2,4-dinitro benzene (CDNB) as the limiting substrate the inhibition is competitive in each case. At a GSH concentration of 5 . 10(-3) M the inhibition constants for transferases A and C at 25 degrees C are similar and very low, 3.2 . 10(-8) M and 5.6 . 10(-8) M respectively, whereas for transferase B the inhibition constant is 3.5 . 10(-5) M. Equilibrium-dialysis experiments carried out at 4 degrees C in the absence of GSH give apparent dissociation constants of 7.1 . 10(-4) M and 3.4 . 10(-4) M for transferases A and B respectively, but if 5 . 10(-3) M glutathione is included in the dialysis solutions these values fall to 2.0 . 10(-7) M and 2.6 . 10(-5) M, which are within an order of magnitude of the kinetic Ki-values. Chromatographic experiments with Sephadex G-10 show that GSH and SnEt3 interact in aqueous solution under the conditions of the enzyme-kinetic and equilibrium-dialysis experiments. It is suggested that the inhibited enzymes are in the form of ternary complexes, enzyme-GSH-SnEt3, in which GSH and SnEt3 may or may not interact directly; or are possibly quaternary complexes, enzyme-(GSH)2-SnEt3. SnEt3 could be valuable as a selective inhibitor of transferases A and C in mixtures of the three transferases.

Animals↗
PubMed1986

Diurnal patterns in homecage behavior of rats after acute exposure to triethyltin.

Diurnal patterns of eating, drinking, locomotor activity, and rearing in male Fischer-344 rats were examined for 11 days after a single oral dose of triethyltin bromide (TET) at 0, 1.5, 3, or 5 mg/kg. The 5 mg/kg group exhibited a time-related drop in food consumption and body weight until 3 of 10 rats were sacrificed moribund 11 days after dosing. Doses of 1.5 and 3 mg/kg TET did not reduce body weight or consumption of food and water. In contrast, food consumption was significantly increased 7 and 11 days after 3 mg/kg TET, and diurnal patterns of eating and drinking were disrupted 7 days after 3 and 5 mg/kg TET. A phase shift in licking patterns was induced by the high dose. Unlike trimethyltin (TMT), TET did not affect efficiency of eating. Diurnal patterns of both horizontal and vertical activity were disrupted at all dose levels on Day 2 after dosing; by 16 days after dosing, recovery was evident in all rats including those surviving 5 mg/kg TET. These results show that a near-lethal dose of TET produced a reversible syndrome of hypoactivity, aphagia, and weight loss similar to that seen after acute TMT; in the absence of the above signs, diurnal patterns of behavior revealed effects of TET at doses as low as 1.5 mg/kg; the magnitude of the effect depended on the time of day at which the response was measured; and TET did not produce the same effects on ingestive behaviors (polydipsia and reduced feeding efficiency) that were previously observed after acute TMT.

Animals↗
PubMed1983

Comparative developmental toxicity of triethyltin using split-litter and whole-litter dosing.

Previous work in our laboratory suggested that toxicity resulting from acute postnatal administration of triethyltin (TET) was influenced by the treatment condition of littermates. To test this possibility, two dosing models were compared. For the split-litter model (N = 20 litters/dose), 1 male and 1 female pup per litter received a single dose of O (saline), 3, 6, or 9 mg TET/kg on postnatal d 5; the remaining 6 littermates were not injected. In the whole-litter model, all 8 littermates received 0, 3, 6, or 9 mg TET/kg (N = 5 litters/dose). Differences between dosing models were found for preweaning body weight and adult figure-eight maze activity. Body weights were reduced in all TET-dosed pups; for 3-mg/kg animals, the reduction in preweaning growth was more persistent for pups in the split-litter group. Motor activity in a figure-eight maze was increased in both 6- and 9-mg/kg animals; for the high dose, the increase in activity was greater for animals in the split-litter group. There were no differences between dosing models in mortality, brain weight, or postweaning body weight. Approximately 50% of the 9-mg/kg animals died; there was no treatment related mortality at lower doses. Adult body weight also remained decreased only in the 9-mg/kg animals. Brain weight was reduced for all TET dose groups. These results indicate that developmental toxicity produced by TET is not primarily determined by the dosing regimen.

Animals↗
PubMed1989

Proton magnetic resonance studies of triethyltin-induced edema during perinatal brain development in rabbits.

To better understand the role of myelin-associated water in the differentiation of white and gray matter in magnetic resonance (MR) imaging, changes in MR relaxation processes were studied in rabbits during myelination and after induction of cytotoxic edema with triethyltin (TET). Normal rabbits were killed at various age intervals ranging from premature (28 days' gestation) to adult, and changes in MR relaxation times (T1 and T2) and in water and electrolyte content were determined for various areas of brain and muscle. Similar measurements were made in rabbits of comparable age exposed to TET. Light and electron microscopy and MR imaging were used to follow myelin development and morphological changes induced by TET. During the first 30 postnatal days, both T1 and T2 declined by 50% in normal rabbits, a fall that paralleled the loss in brain water and sodium that occurred during the same period. Exposure to TET prolonged T1 and T2 in white but not gray matter, reflecting the accumulation of sodium and water (edema fluid) in white matter areas. Multiexponential analysis revealed a second, longer component in T2 magnetization decay of TET-exposed white matter, presumably attributable to accumulation of non-ordered water within intramyelinic vacuoles, a supposition consistent with electron microscopic and MR imaging findings. In contrast to reports by others, changes in T1 (but not T2) closely correlated with alterations in brain water (r = 0.93, df = 39). The absence of tissue disruption in the animals in the present study may account for these differences, but further studies will be required both to resolve this question and to fully understand MR images of white matter edema in mature and immature brain.

Aging↗
PubMed1983

Immediate and long-term alterations in maximal electroshock seizure responsiveness in rats neonatally exposed to triethyltin bromide.

Neonatal rats were injected (sc) with 0, 0.25, 0.5, 1.0, 2.5, or 5.0 mg/kg triethyltin bromide (TET) in a 2% ethanol vehicle on Days 0, 5, 10, 15, and 20 postnatally. TET-exposed neonates exhibited a dose-dependent delay in the ontogenetic appearance of both the clonic and tonic maximal electroshock seizure (MES) responses which were apparent up to Day 45, as evaluated by the MES grade distributions and the durations of the individual phases of the MES. In marked contrast, adult rats (exposed to TET only as neonates) exhibited long-term increases in MES severity, as evaluated by the durations of the individual phases of the MES. At 75 days of age, a time when the 1.0 mg/kg developmentally TET-treated group exhibited an increased seizure severity, a single challenge dose of 1.0 mg/kg TET (ip) produced a proportional decrease in MES severity in both developmentally treated and control rats. No changes in preweaning or postweaning body weight were observed in the animals in the 0.25, 0.5, 1.0, or 2.5 mg/kg groups. A 30% decrease in weaning weight and an approximate 15% decrease in postweaning weight were observed in the 5.0 mg/kg group. These seizure results demonstrate that developmental exposure to TET produces immediate and long-term alterations in central nervous system functioning, which are of an opposite character. Interesting, we have previously shown that developmental lead exposure produces a similar developmental/adult dichotomy of effects with regard to the MES severity; however, the two patterns are reversed (D. A. Fox, S. R. Overmann, and D. E. Woolley (1979).

Aging↗
PubMed1987

Effects of an extract of Ginkgo biloba on the 3',5'-cyclic AMP phosphodiesterase activity of the brain of normal and triethyltin-intoxicated rats.

For clarification of the beneficial effects of the extract of Ginkgo biloba (EGB) on triethyltin (TET) toxicity in rats, the phosphodiesterase (PDE) activities of the cerebral tissue were measured under in vitro and ex vivo conditions. Under in vitro conditions, low concentrations of EGB (0.25-4.0 mg/L) activated the enzyme, whereas after higher concentrations (5-250 mg/L), dose-dependent inhibition of the enzyme activity was observed. In the lower concentration range, the extract also partially restored the high-affinity PDE activity (measured with 0.25 microM cyclic AMP) of the particulate fraction of the brain inhibited by TET in vitro. In contrast, the inhibitory influence of TET on the low-affinity PDE activity (measured with 50 microM cyclic AMP) of the particulate fraction was enhanced by the extract. Although treatment with a single large dose of EGB lowered the particulate PDE activities of the brain of normal rats, no effects of the extract could be detected in animals after repeated daily administrations of EGB during a 4-day period. Curative treatment of the TET-intoxicated rats with EGB during a 7-day period accelerated the recovery of the edematous state of the white matter caused by the intoxication and also normalized the lowered PDE activity of the particulate fraction of the edematous brain tissue. Furthermore, when preventively administered, EGB counteracted both the edema formation and the fall in PDE activity observed with treatment by TET alone. These observations strongly suggest that some beneficial effects of EGB might be due to its modulating influences on cellular cyclic AMP levels via activation of membrane-bound PDE.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1983

Triethyltin decreases maximal electroshock seizure severity in adult rats.

Acute and subacute treatment of adult rats with triethyltin bromide (TET) caused dose-dependent and time-dependent decreases in maximal electroshock seizure (MES) severity. This decrease in excitability was characterized by both a decrease in the percentage of animals exhibiting a maximal seizure and a corresponding decrease in the extension durations and an increase in the flexion durations. Acutely treated rats received (ip) 0, 1, or 5 mg/kg TET while subacutely exposed (po) received 0, 1, 5, or 10 ppm TET in the drinking water for 10 days. Experiments were designed so that the total consumed dose of TET, on a milligram per kilogram basis, equaled that in the acute experiment. No alterations in body weight were observed in either experiment. Acutely, the onset of action of TET was detectable within 0.5 hr. For the 1 mg/kg group, the effect peaked between 4 and 24 hr and completely recovered by 72 to 96 hr. For the 5 mg/kg group, the marked effect peaked at 4 hr, however, no recovery was observed. Subacute exposure for 1 to 2 days produced marked decreases in MES severity which were still present in the 5- and 10-ppm groups 14 days after cessation of exposure. Comparison of the onset and recovery data in the acute and subacute experiments revealed a close correspondence in similarly dosed rats. Comparison with other MES data from our laboratory revealed that adult rats were more sensitive to TET than adult mice or developing rats. Additionally, the MES test was able to detect subtle functional alterations in the central nervous system at lower doses of TET than previously reported neurobehavioral evaluation procedures.

Animals↗
PubMed1984

Tin distribution in adult and neonatal rat brain following exposure to triethyltin.

The uptake, distribution, and elimination of tin were determined in adult and neonatal (Postnatal Day 5) rat brain following ip administration of triethyltin bromide (TET). Groups of five adult CD rats were killed at 10 min, 1 hr, 4 hr, 24 hr, 5 days, or 10 days following acute exposure to 6.0 mg/kg TET; an additional group of adult animals was killed at 24 hr following exposure to either 3.0, 6.0, or 9.0 mg/kg (N = 5/dosage). The time course for tin distribution in 5-day-old rat pups was determined by killing pups 10 min, 30 min, 1 hr, 4 hr, 8 hr, 12 hr, 24 hr, 5 days, 10 days, or 22 days following exposure to either 3.0 or 6.0 mg/kg TET (N = 4/dosage/time). Tin analyses were performed by flameless atomic absorption spectrophotometry. The t1/2 for total tin in the adult rat brain following 6.0 mg/kg TET was determined to be 8.0 days. The maximum concentration in the adult was reached at 24 hr and corresponded to 4.6, 9.6, and 16.6 ng tin/mg protein for dosages of 3.0, 6.0, and 9.0 mg/kg, respectively. Tin was evenly distributed across all brain areas studied. For animals exposed to 6.0 mg/kg TET on Postnatal Day 5, the t1/2 for total tin in the brain was 7.3 days. A maximum concentration of 9.9 ng tin/mg protein was reached at 8 hr postexposure. The rate of elimination of tin from the brain (as measured by the elimination rate constant kel) did not differ significantly between adults and neonates. However, due to a dilution effect by the rapid brain growth of the neonate, the concentration of tin in the neonatal brain following TET administration decreased significantly faster than that in the adult.

Animals↗
PubMedDate not supplied

Effects of triethyltin on responding of mice under a multiple schedule of reinforcement.

The lethality and behavioral effects of triethyltin (TET) were determined in adult, male BALB/c mice. Following a single IP dose of TET (10, 12.5 or 15 mg/kg), the lethality was determined at 24-hr intervals. By 144 hr after TET administration, lethality had risen to greater than 90% in the groups receiving the 12.5 and 15 mg/kg and 20% (6/30) in the group which received 10 mg/kg. No additional deaths were observed over the remainder of the two week observation period. The behavioral effects of 5, 7.5 or 10 mg/kg were determined in mice trained to respond under a multiple fixed-ratio 30, fixed-interval 600-sec schedule of milk presentation. At 3 hr after TET administration, the rate of responding was decreased at all three doses. However, by 27 hr after 5 or 7.5 mg/kg TET the rate of responding had returned to pre-injection control values while the responding of the mice in the 10 mg/kg group did not return to pre-injection control values until 51 hr after administration. In a separate group of mice, 7.5 mg/kg was administered at 2 week intervals for a total of 5 separate administrations. No evidence for a cumulative or diminished behavioral effect was observed. Neuropathological examination revealed a direct dose and time related pathology in the white matter of the CNS. Maximal edematous vacuolar change was observed 72 hr after TET administration. Such morphological changes, however, were totally absent 12 days after a single 10 mg/kg exposure. Multiple exposure to TET (7.5 mg/kg) at 2 week intervals for 10 weeks showed only minimal morphological alterations in the brain.

Animals↗
PubMed1984

Vascular permeability in acute triethyltin-induced brain edema studied with FITC-dextrans, sodium fluorescein and horseradish peroxidase as tracers.

In golden hamsters, a study was made on the vascular permeability changes which might take place during the formation of triethyltin (TET)-induced brain edema. For this purpose, the animals received a single intravenous (i.v.) injection of TET sulphate (5-10 mg/kg b.wt) and groups of animals were studied 4 to 24 h thereafter. By the use of a new density gradient technique based on polyvinylcoated silica particles (1), it was shown that white matter edema was present already at 4 h after the TET injection. The edema then progressed during the following 20 h. Electron microscopy revealed that fluid accumulated in myelin vacuoles of the hamsters in the same way as has been described in other animal species. The macromolecular tracer, horseradish peroxidase mol.wt 40,000 injected i.v., did not leak out of the cerebral vessels during the period when edema developed. In order to find out if the formation of edema is associated with a vascular permeability increase to other and smaller markers, we used several fractions of FITC-dextrans varying from mol.wt 3,000 to 70,000 and determined their intracerebral localization with a histotechnical procedure. FITC-dextrans, mol.wt 70,000, did not leak out of the cerebral vessels in any of the TET intoxicated hamsters during the observation period of 24 h. The same was true for most animals given the other dextran fractions. However, FITC-dextrans, mol.wt 3,000-20,000 were present outside the vessels in the edematous optic nerves and corpus callosum in a few TET treated animals taken 16-24 h after the TET injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1977

Effect of triethyltin on Escherichia coli K-12.

Triethyltin (TET) stimulated the basal respiration of Escherichia coli K-12 membrane vesicles in chloride (Cl-) medium but it had little effect on respiration in sulphate (SO4(2-)) medium. Since this uncoupling activity was Cl- dependent it was attributed to the Cl-/hydroxide (OH-) exchange reaction known to be mediated by TET [1,2]. TET inhibited the oxidation of succinate by intact E. coli in both Cl- and SO4(2-) medium, but at the same concentration of TET, inhibition was always more extensive in Cl- than SO4(2-) medium. In Cl- medium uncoupling in membrane vesicles and inhibition of succinate oxidation in intact bacteria occurred over the same concentration range and it appeared that the same mechanism, i.e. Cl-/OH- exchange, was responsible for both effects. Inhibition of succinate oxidation in SO4(2-) medium was not substantial until the concentration of TET was greater than 10(-5) M. Although the nature of this inhibition could not be determined by experiments with membrane vesicles indirect evidence from growth experiments indicated that it was due to impairment of oxidative phosphorylation. The relationship between these biochemical findings and the bacteriocidal action of TET was examined by using various concentrations of anion and substrate in the growth medium. Growth was inhibited in media containing either Cl- or SO4(2-) as the main anion but at a particular concentration of TET, inhibition was greater in Cl- medium. Growth was also inhibited to a greater extent in succinate than glucose medium. Furthermore in either Cl- or SO4(2-) glucose medium, lactic acid production increased as the concentration of TET was increased. These findings imply that the bacteriocidal action of TET is related to its effect(s) on oxidative phosphorylation.

Adenosine Diphosphate↗
PubMed1984

Pre- and postweaning indices of neurotoxicity in rats: effects of triethyltin (TET).

Pre- and postweaning measures of learning and locomotor activity were used as indices of CNS function after early perinatal neurotoxic insult. Triethyltin (0.0, 3.0, or 6.0 mg/kg, ip) administered on Postnatal Day 5 (PND5) was used as the neurotoxicant. Learning deficits and alterations in locomotor activity were observed during both the pre- and postweaning periods. Preweaning learning ability was evaluated with an appetitive alleyway paradigm, while an automated radial-arm maze (RAM) was used to assess juvenile learning. Preweaning open-field locomotion was evaluated in the presence and absence of homecage litter while postweaning activity was measured in an automated device, the Motron, or as a component of performance in the RAM. The 6.0-mg/kg TET-exposed animals required more trials to acquire the alleyway task. RAM subjects receiving 6.0 mg/kg of TET were less accurate than those given 3.0 mg/kg or vehicle control. TET did not affect open-field activity on PND10; low levels of spontaneous locomotion occurred regardless of treatment. On PND13, there was a dose-related decrease in locomotion over home-cage litter while all groups exhibited equivalent low rates of locomotion in the absence of home-cage cues. All treatment groups were more active when tested over litter than over no litter. In contrast, on PND21 and throughout the RAM testing period, TET-exposed subjects exhibited dose-related increases in activity. TET produced treatment-related decreases in wet weight of whole brain, hippocampus, and cerebellum in both developing (PND23) and adult (PND200) animals with the hippocampus being most affected on a percentage basis. In contrast, no treatment-related body weight differences were observed at these times. The neurotoxicity of TET can be demonstrated during the preweaning period whether a commonly used endpoint in assessing CNS function (locomotor activity) is monitored or a more complex endpoint (learning) is evaluated provied (1) the method used to monitor locomotor activity incorporates both the normally low levels of preweaning locomotion and the more elevated levels induced by home-cage cues and (2) the learning paradigms utilized are appropriate for the capabilities of the animal.

Animals↗
PubMed1988

Acute exposure of the neonatal rat to triethyltin results in persistent changes in neurotypic and gliotypic proteins.

Measurements of neuron-specific (neurotypic) and glia-specific (gliotypic) proteins were used to characterize the toxic effects of triethyltin (TET) on the developing central nervous system. Six proteins, each of which is associated with specific aspects of neuronal and glial development, were evaluated as follows: 1) neurofilament-200, an intermediate filament protein of the neuronal cytoskeleton; 2) synapsin I, a synapse specific, synaptic vesicle localized protein; 3) p38, another synaptic-vesicle localized protein; 4) myelin basic protein, a protein unique to myelin-forming oligodendroglia; 5) glial fibrillary acidic protein, the intermediate filament protein of astrocytes; and 6) beta-tubulin, a constituent primarily of neuronal microtubules. The amount of each protein in homogenates of hippocampus, forebrain and cerebellum, brain regions with different developmental profiles, was determined by radioimmunoassay. After a single administration on postnatal day 5, TET (3 or 6 mg/kg i.p.) caused permanent dose- and region-dependent decrements in brain weight, with the hippocampus being the most affected. These effects were not associated with light microscopic evidence of cytopathology but were accompanied by large dose-, time- and region-dependent alterations in all neurotypic and gliotypic proteins evaluated. On a per structure (total) basis, TET caused permanent decreases in most neurotypic and gliotypic proteins in all areas. On a per milligram of tissue protein (concentration) basis, changes in specific proteins also were observed in all regions but were most prevalent in hippocampus and cerebellum. In hippocampus and cerebellum, decrements in the concentration of neurotypic and gliotypic proteins were observed in the absence of TET-induced decreases in the weights of these structures. The data indicate that 1) neonatal exposure to TET causes permanent deficits in neuronal as well as glial development, 2) the effects of TET are region-dependent but do not appear to be related to region-dependent stages in development and 3) assays of neurotypic and gliotypic proteins may be used to characterize the temporal and regional patterns of neuronal and glial responses to toxic exposures of the developing central nervous system.

Animals↗
PubMed1979

Inhibition of the enzymatic activity of ligandin by organogermanium, organolead or organotin compounds and the biliary excretion of sulfobromophthalein by the rat.

Ligandin binds several classes of compounds, has glutathione-S-transferase activity and is postulated to function in the intracellular transport of substances which bind to it and/or are substrates for its enzymatic activity. The effects of a group of organometals reported to inhibit the enzymatic activity of ligandin on the biliary excretion of sulfobromophthalein have been investigated to determine what role the enzymatic activity of ligandin has with respect to the biliary excretion of the dye. Triethyllead reduced the rate of dye excretion into the bile without affecting blood pressure, blood or liver sulfhydryl compounds or the volume of bile flow. The organometal had no effect on the initial rate of plasma dye clearance. Inhibited biliary sulfobromophthalein excretion by triethylead-treated rats correlated with relative increases in liver and bile unconjugated dye, decreases in liver and bile conjugated dye and reduced glutathione-S-aryltransferase activity in supernatant fractions isolated from the liver. The results clearly demonstrated that the tested organometals can inhibit the enzymatic activity of ligandin in vivo and suggested that, if ligandin has a role in the translocation of the dye from the blood to the liver, the enzymatic activity of the protein may not be involved.

Animals↗