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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of chlorophenothane (pp'--DDT) and five structurally related compounds op-DDD (op'-DDD, pp'-DDD, DTE, DCMP and DCP see text) on the cerebral hemisphere gamma-aminobutyric acid (GABA), the main inhibitory transmitter in brain contents and possible correlation with central activities was demonstrated in rats. The tested compounds were given in oral doses of 600 mg/kg in peanut oil. Cerebral GABA content was determined 1, 3 and 6 hrs after the ingestion of pp'-DDT and 3 hrs after each of the other drugs. The mean GABA content in each group of rats was compared with control groups, either without any treatment, or receiving the equivalent volume of peanut oil. pp'-DDT produced a significant reduction in brain GABA contents 3 and 6 hrs after its administration. This was accompanied by excitability, tremor and clonic convulsions. Of the congenors, only DTE exerted a similar effect. The present results point to the possibility of partial involvement of GABA in the tremor and convulsions induced by pp'-DDT. They also indicate the importance of the CCl2 grouping in the molecule for the induction of central effects of pp'-DDT.
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PMID:Investigation of the effect of chlorophenothane and certain chemically related compounds on the cerebral gamma-aminobutyric acid contents in rats. 74 May 48

DDT was administered to the guinea pig, mouse and rat either ig or ip and to the hamster ig in order to investigate variations in the response of hepatic and duodenal drug-metabolizing enzymes to DDT. The intragastric dose (160 mg/kg) was found to produce gastric bleeding and severe tremor in rats and mice but not in other rodents. The hepatic aryl hydrocarbon hydroxylase activity and cytochrome P-450 concentration decreased after the ig administration of DDT to rats, mice and guinea pigs but in hamsters the activiy of aryl hydrocarbon hydroxylase and cytochrome P-450 concentration increased 12 hr after the dosage. The aryl hydrocarbon hydroxylase activity decreased also in the duodenal mucosa of the rat after the ig administration of DDT. The ip dose had no effects on the hepatic or duodenal monooxygenase system in 12 hr. The UDPglucuronosyltransferase activity was slightly lowered in hepatic microsomes of the rat and mouse after the ig dose of DDT, but the decrease was more profound when measured after in vitro trypsin digestion of microsomes. The trypsin digestion activated the hepatic UDPglucuronosyltransferase in all the species studied, i.e., guinea pig, hamster, mouse and rat (3-, 3-, 5-, and 8-fold, respectively). The duodenal UDPglucuronosyltransferase activity was not affected by DDT administration in any of the species studied. The results suggest that the acute toxic effects of DDT are species-dependent and the administration route is important in DDT toxicity. The hydroxylation step in drug metabolism is more sensitive to DDT than the glucuronidation step.
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PMID:Effect of administration route on DDT on acute toxicity and on drug biotransformation in various rodents. 81 74

Inbred Swiss mice were treated with technical DDT (1) orally with the diet or by intubation; (2) subcutaneously and (3) by skin painting. The total duration of the experiment was 80 weeks. There was no difference in body growth and mortality between the experimental and control groups. Toxic manifestations of DDT were observed in treated mice in the form of tremor, convulsions and corneal opacity usually after 40 weeks. Oral and subcutaneous DDT treatment resulted in a significant increase in the incidence of tumours mainly of lymphoid tissues, lung and liver. The highest tumour incidence was recorded in the group of mice receiving DDT by subcutaneous injections. Males and females were equally susceptible. No evidence of carcinogenicity was observed in the painted group.
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PMID:Carcinogenicity of DDT (dichlorodiphenyl trichloroethane) in pure inbred Swiss mice. 86 49

Difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase (ODC; 200-800 mg/kg, s.c.), to rats has no detectable behavioral effects using a battery of tests to assess sensorimotor function. In contrast, the induction of tremor by chlordecone, a neurotoxic agent that affects neuronal ionic processes, is significantly attenuated by pretreatment with DFMO. The effects of DFMO on chlordecone-induced tremor were reversed by pretreatment with putrescine. DFMO had no effects on p,p'-DDT, a tremorigen having a mechanism of action different from chlordecone. These findings imply that polyamines may play a role in select neuronal processes.
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PMID:Inhibition of ornithine decarboxylase alters neurological responsiveness to a tremorigen. 242 59

Rats were given 75 mg/kg of 5,5-diphenylhydantoin (phenytoin) or vehicle 30 min prior to 75 mg/kg of 1,1,1-trichloro-bis(p-chlorophenyl)ethane (p,p'-DDT) (p.o.) or chlordecone (i.p.) and tremor was measured 12 h later. Rats were then killed, and regional brain levels of biogenic amines and their acid metabolites and amino acids were determined. Pretreatment with phenytoin significantly attenuated the tremor produced by p,p'-DDT but enhanced that produced by chlordecone. p,p'-DDT had significant effects on the levels of aspartate, glutamate, 5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG), whereas chlordecone increased glycine, 5-HIAA, and MHPG levels. Pretreatment with phenytoin blocked p,p'-DDT-induced increases of aspartate in the brainstem and spinal cord, 5-HIAA in the hippocampus, and MHPG in the brainstem and hypothalamus. Phenytoin significantly enhanced chlordecone-induced increases of MHPG in the brainstem. These data indicate that organochlorine-induced increases in noradrenergic activity in the brainstem and spinal cord may be directly related to the tremorigenic effects of these chemicals.
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PMID:5,5-Diphenylhydantoin antagonizes neurochemical and behavioral effects of p,p'-DDT but not of chlordecone. 243 63

p,p'-DDT and related agents act to hold the sodium channel open once opened and this effect is believed to be responsible for neurological effects of tremor and hyperexcitability in vivo. There is a good correlation between DDT-induced tremor and an increase in the levels of the metabolites of norepinephrine (NE), serotonin (5HT) and, to a lesser extent, dopamine (DA) in the brain stem (BS), hypothalamus (HYP), striatum (STR), or hippocampus (HPC). DDT also increases levels of excitatory amino acids glutamate (GLU) and aspartate (ASP), but the effect occurs only in the brain stem. These effects are dose- and time-related. Pharmacological studies found that blockade of alpha 1-adrenergic receptors attenuate DDT-induced tremor, while blockade of serotonergic, cholinergic muscarinic, and dopaminergic receptors augment the toxicity of DDT. Tremor was almost completely blocked in rats pretreated with hydantoin, an anticonvulsant believed to block repetitive firing of nerves by interfering with the inactivation gate of the sodium channel. A similar antagonism was observed for permethrin, a Type I pyrethroid believed to have a mechanism of action very similar to that of DDT. However, hydantoin increased the tremorigenic effects of chlordecone, an organochlorine whose mechanism has not been linked to the sodium channel. These data are consistent with the hypothesis that the in vivo neurotoxicity of some organochlorine insecticides is related to their effects on the sodium channel.
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PMID:Neurochemical effects of DDT in rat brain in vivo. 243 59

Pretreatment of rats with phenoxybenzamine (5 mg/kg; SC), an alpha adrenergic antagonist, decreased the peak tremor power and startle magnitude of rats subsequently given DDT (75 mg/kg; PO) or chlordecone (60 mg/kg; IP), without having a significant effect on control animals. Pretreatment with an intracerebroventricular injection of calcium (3.75 microM in 5 microliters NaCl) decreased the peak tremor power due to subsequently administered DDT, while increasing the tremor response in rats later dosed with chlordecone. The effects of phenoxybenzamine are postulated to be due to a blockade of an excitatory influence of the adrenergic system. Calcium may decrease DDT-induced tremor by acting as a neuronal stabilizer. Potentiation of the tremorigenic effect of chlordecone by calcium may be due to increased levels of intracellular calcium, resulting in augmented release of neurotransmitters in chlordecone-exposed animals.
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PMID:Pharmacological modification of tremor and enhanced acoustic startle by chlordecone and p,p'-DDT. 243 48

Japanese quail eggs were injected with 1-(2-chlorophenyl)-1-(4-chlorophenyl)-2,2,2-trichloroethane o,p'-DDT(1-10 mg),1,1-bis(4-chlorophenyl)-2,2,2-trichloroethane p,p'-DDT (1-10 mg), or, in one study, 0.5 mg chlordecone dissolved in 50 microliters of corn oil on day 1 of incubation. Hatchability was not decreased by o,p'-DDT or p,p'-DDT, as compared to corn-oil-injected controls, but was reduced in progeny of parents injected in ovo with either isomer. Tremor was observed for up to 4 days posthatching only in birds injected with 1.75-10 mg p,p'-DDT or chlordecone. Survivability to 5 weeks posthatch was reduced (less than or equal to 50%) in birds injected in ovo with 6.25-7.5 mg, o,p'-DDT or 1.75-5 mg p,p'-DDT as compared to corn oil (96%). Reproductive behaviors were attenuated in birds injected during development with o,p'-DDT, both DDT isomers decreased the total number of ovipositions, and o,p'-DDT increased the total number of eggshell malformations. Neither body weights nor reproductive organ weights at 12 weeks were affected by injection of either isomer. Exposure to DDT did not affect acquisition of a matched-to-sample food-reinforced response or subsequent responding on a random interval schedule of reinforcement. In another experiment, total circulating erythrocyte numbers were reduced in females after injection in ovo with o,p'-DDT but not after injection with p,p'-DDT. A primary humoral immune response was not affected by in ovo exposure to either isomer of DDT. In ovo exposure to o,p'-DDT but not to p,p'-DDT had long-term and estrogen-like effects on behavior and hematology in Japanese quail. Posthatch primary feather morphology was also altered by embryonic exposure to o,p'-DDT, p,p'-DDT, and chlordecone.
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PMID:Exposure of Japanese quail embryos to o,p'-DDT has long-term effects on reproductive behaviors, hematology, and feather morphology. 247 19

Organochlorine insecticides such as DDT and chlordecone produce tremor in exposed individuals. Using a spectral analysis technique, chlordecone-induced tremor in rats was found to be dose- and time-related and could be distinguished from pharmacological agents (i.e., harmine, oxotremorine, and apomorphine) that produce tremor or stereotypic behavior. Drugs with known pharmacological effects were used to study the possible mechanism of chlordecone-induced tremor. Although no one neurotransmitter system appears necessary for tremor, the serotonergic, gabaergic, and cholinergic systems appear to contribute to chlordecone-induced tremor. The role of the catecholaminergic system is uncertain. Subsequent experiments indicated that supraspinal processes, possibly located in the brain stem, are important contributors to chlordecone-induced tremor. Activation of the cerebellum via the olivocerebellar tract to produce tremor cannot explain chlordecone's tremorgenic effects.
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PMID:Studies on the mechanism of chlordecone-induced tremor in rats. 258 Nov 96

Male, Fischer strain 344 adult rats were given various doses (25-100 mg/kg) of p,p'-DDT by oral gavage, and levels of biogenic amines, their metabolites, and amino acid neurotransmitters, tremor activity, and rectal temperature were measured at several intervals (2, 5, 12, and 24 h) after dosing. Dose-related increases in rectal temperature and in tremor activity were observed at 50-100 mg/kg 12 h after dosing. Tremorigenic doses of DDT increased the 5-hydroxyindoleacetic acid (5-HIAA) level in hypothalamus, brainstem, and striatum, whereas doses of 75 and 100 mg/kg increased the 3-methoxy-4-hydroxyphenylglycol (MHPG) level in hypothalamus and brainstem and the 3,4-dihydroxyphenylacetic acid level in striatum. Six amino acids were assayed in the brainstem, hypothalamus, and striatum; aspartate and glutamate levels were increased only in brainstem at 25-100 mg/kg. No consistent changes in concentrations of taurine, glutamine, glycine, or gamma-aminobutyric acid were observed in any of the regions assayed. Time-related increases in rectal temperature were seen 2-12 h after dosing, and the presence of tremor was observed 5-12 h after dosing; for both the time of peak effect was at 12 h. The DDT-induced hyperthermia and tremor were associated with dose- and time-related increases in levels of 5-HIAA, MHPG, aspartate, and glutamate. It is suggested that an increase in the turnover rate of 5-hydroxytryptamine (5-HT) may be responsible for the DDT-induced hyperthermia, whereas increases in the metabolism of 5-HT and norepinephrine may be involved in the tremor.
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PMID:Effects of p,p'-DDT on the rat brain concentrations of biogenic amine and amino acid neurotransmitters and their association with p,p'-DDT-induced tremor and hyperthermia. 286 92


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