triethyltin and Body-Weight

The effect of hexachlorophene (HCP; 2,2'-methylenebis(3,4,6-trichlorophenol), cuprizone (CPZ; bicyclohexone oxaldihydrazone) and triethyl tin (TET; triethyl tin sulphate) in producing vacuoles in the brain of the Sprague-Dawley rat has been quantified by image analysis of the extent of the spongy change in the white matter. The state of the astrocytes was assessed by immunocytochemical staining for glial fibrillary acidic protein (GFAP). HCP and TET caused a dose-related spongiosis, but cuprizone had no significant effect on the brain. With chronic HCP treatment, the spongiosis was accompanied by astrocyte hypertrophy and proliferation, and the extent of the gliotic reaction was related to the dose of HCP. The results demonstrate that HCP can produce and maintain astrocyte proliferation in the rat brain. Such an agent was required for use in an investigation of a putative tumour promoter in the rat.

Topics: Animals; Body Weight; Brain; Brain Edema; Cuprizone; Dose-Response Relationship, Drug; Drinking; Eating; Hexachlorophene; Male; Organ Size; Rats; Rats, Inbred Strains; Triethyltin Compounds; Vacuoles

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.

Topics: Animals; Animals, Newborn; Body Weight; Brain; Cerebellum; Female; Glial Fibrillary Acidic Protein; Hippocampus; Immunosorbent Techniques; Male; Nerve Tissue Proteins; Organ Size; Radioimmunoassay; Rats; Trialkyltin Compounds; Triethyltin Compounds

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.

Topics: Animals; Behavior, Animal; Body Weight; Circadian Rhythm; Drinking Behavior; Feeding Behavior; Male; Motor Activity; Rats; Trialkyltin Compounds; Triethyltin Compounds

Although fluid restriction is often used to manage cerebral edema, there have been no controlled studies which demonstrate its benefit. We evaluated the effects of dehydration and overhydration on the development of cerebral edema in rats subjected to triethyltin poisoning or anoxic ischemia. Four days after triethyltin poisoning, the brains of control rats receiving maintenance hydration had a mean percentage of water of 79.56%; dehydration (5% of body weight) and overhydration groups were not statistically different at 79.95% and 79.86%, respectively. Forty-seven hours after an anoxic-ischemic insult consisting of unilateral carotid artery ligation and subsequent exposure to a 4% oxygen atmosphere for 30 min, the percentage of water in control rats was 79.12%; dehydration (13% of body weight) and overhydration groups were 79.10% and 79.16%, respectively. Histopathologic analysis of brain sections did not differentiate the hydration groups (triethyltin model only). Thus, cerebral edema was not altered by hydration status in either poisoned or ischemic animals.

Topics: Animals; Body Weight; Brain Chemistry; Brain Diseases; Brain Ischemia; Edema; Female; Fluid Therapy; Rats; Rats, Inbred Strains; Triethyltin Compounds; Water

Cadmium (Cd), triethyltin (TET), and trimethyltin (TMT) are heavy metals which are neurotoxic to developing animals. In the present experiment, preweaning assessment of locomotor activity was used to detect and differentiate between the developmental toxicity of these metals. On postnatal day (PND) 5, rat pups received a single injection of either Cd, TET, or TMT. A within-litter design was used for dosing; 1 male and 1 female pup from each litter (N = 10 litters/compound) received either the vehicle, low, medium, or high dosage of the compound. Preweaning motor activity was assessed in 30-min sessions in figure-eight mazes from PND 13 to 21. Motor activity of control animals progressively increased in the initial days of testing, and then both within-session and between-session habituation developed. A single exposure to Cd, TET, and TMT produced hyperactivity by the end of the preweaning period but these metals differed in the day of peak activity, the onset of hyperactivity, and the development of habituation.

Topics: Animals; Animals, Suckling; Body Weight; Cadmium; Dose-Response Relationship, Drug; Female; Male; Metals; Motor Activity; Rats; Sex Factors; Time Factors; Triethyltin Compounds; Trimethyltin Compounds

The behavioral effects of both acute and subacute triethyltin (TET) exposure were examined in the rat. Animals acutely exposed to TET at doses of 0, 1.5 and 3.0 mg/kg showed a dose-related decrease in motor activity when tested between 2 and 4 hr following exposure. Subacute (3 week) exposure to TET in the drinking water (5 or 10 ppm) resulted in performance decrements in the following: maze activity, open field behavior, acoustic startle response and landing foot-spread. Early signs of behavioral deficits were observed 2 weeks after 10 ppm TET. These effects were reversible within one month after termination of exposure.

Topics: Animals; Behavior, Animal; Body Weight; Drinking; Male; Maze Learning; Motor Activity; Neurotoxicity Syndromes; Rats; Reflex, Startle; Triethyltin Compounds