dieldrin and Seizures

The application of a constant-amplitude electrical stimulation to many parts of the brain leads to the expression of progressively more severe epileptiform responses. The process of acquisition is termed kindling, and the acquired response is termed the kindled seizure. This state has been used in a number of important ways including the modeling of human epilepsy and behavioral disorders, the testing of drugs for anticonvulsant effects, and, more recently, the examination of hyperexcitability states induced by pesticides and other environmental chemicals. This report discusses attributes of kindling and kindled seizures, examines possible mechanisms responsible for them, and summarizes drug and chemical effects on them. Kindling is powerfully accelerated by exposures to only a few substances, among the most effective of which are the chlorinated hydrocarbon insecticides, lindane and dieldrin. An analysis of the acceleration of kindling produced by lindane suggests that the threshold concentration in the nervous system for kindling enhancement is approximately 0.4 microgram/g (1.4 X 10(-9) mol/g).

Topics: Acetylcholine; Animals; Anticonvulsants; Brain; Brain Chemistry; Cats; Dieldrin; Dopamine; Electric Stimulation; Electroencephalography; Female; gamma-Aminobutyric Acid; Hexachlorocyclohexane; Kindling, Neurologic; Male; Models, Neurological; Norepinephrine; Primates; Rats; Seizures; Sensory Thresholds; Sex Characteristics; Species Specificity; Time Factors

To reevaluate the toxicity of the organochlorine insecticide and persistent organic pollutant dieldrin and confirm its impact on development, an exposure trial using bird eggs was performed. Dieldrin at concentrations of 10-100 microg/g of egg was injected into the yolks of Japanese quail (Coturnix japonica) eggs. Hatchlings from the eggs were raised to sexual maturity and multiple tests to detect the harmful effects of dieldrin were conducted. Dieldrin at 100 microg/g decreased egg hatchability by 50.0% (vehicle control, 86.7%), although embryogenesis even in unhatched eggs treated with high doses of dieldrin was normal. In safely hatched chicks, dose-dependent early death with tonic seizure was observed and all birds exposed to 100 microg/g died within 3 days. Other significant alterations in hatchlings were enlargement of the whole brain, decreases in mRNA expressions of tryptophan hydroxylase in the brainstem and cholesterol side-chain cleavage in the male gonad, and increases in mRNA expressions of cytochrome P450 1A and 2C18 in the liver. For mature birds (males at 5 weeks and females at 10 weeks of age), impairment of eggshell formation such as reduced eggshell mass and eggshell thinning, increases in the body mass of males and the liver mass of females and increases in serum total cholesterol and triglyceride concentrations were observed. The results indicated that not only does the neurotoxicity of dieldrin bring early death, but its effects on reproductive and hepatic functions (detected as gene transcriptional changes in hatchlings) persist harmfully after maturity.

Topics: Animals; Coturnix; Dieldrin; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Egg Shell; Embryo, Nonmammalian; Female; Male; Ovum; Seizures

Sixteen patients acutely poisoned with aldrin were examined to evaluate a possible correlation between serum aldrin and dieldrin levels and clinical complaints. The patients were classified as having mild (N = 8), moderate (N = 5) or severe (N = 3) poisoning according to clinical symptoms. Concentrations of less than 20 micrograms/l were usually associated with mild poisoning, which involved complaints such as nausea, vomiting and epigastric pain, whereas concentrations of 100 to 200 micrograms/l were considered to represent moderate intoxication and were associated with nausea, vomiting, epigastric pain, headache, dizziness, and convulsions. Severe or fatal cases were associated with levels above 700 micrograms/l. Taken together, these results suggest that serum aldrin and dieldrin levels can be used as indicators of clinical prognosis after acute poisoning with these insecticides and that convulsions could suddenly occur even in the absence of prodromal signs or symptoms.

Topics: Acute Disease; Adolescent; Adult; Aldrin; Child, Preschool; Chromatography, Gas; Dieldrin; Female; Humans; Infant; Male; Prognosis; Seizures

Topics: Animals; DDT; Dieldrin; Male; Mice; Nervous System; Seizures; Tremor

Acute exposure to dieldrin (HEOD) causes hyperglycemia and death in the adult rat. Whether the hyperglycemia contributes to the mortality was studied in 10- and 60-day-old Wistar rats given an LD50 dose of the insecticide (pups, 28 mg/kg p.o. and adults, 63 mg/kg p.o.). HEOD elevated blood glucose 2-fold in the adult but had no effect in the pup. d-Glucose (6 g/kg p.o., 0, 3, 6 and 18 h post HEOD) reduced by 79% the 24-h mortality the insecticide caused in the 10-day-old rat. Thus, hyperglycemia in the immature rat protects against dieldrin toxicity. Conversely, the 24-h mortality was not significantly affected in adult rats whose HEOD-induced hyperglycemia was increased with either d-glucose (6 g/kg p.o., every 2 h post HEOD) or 2-deoxyglucose (1 g/kg s.c., concomitant with the HEOD). Phenobarbital (40 mg/kg i.p., concomitant with the insecticide) significantly decreased both the hyperglycemia (23%) and the 24-h mortality (86%) in HEOD-treated adult rats. The administration of d-glucose (6 g/kg p.o., 0, 3, 9 and 18 h post HEOD) to phenobarbital and HEOD-treated animals restored the hyperglycemia and returned the 24-h mortality to that found in animals given dieldrin alone. Thus, in the adult rat HEOD-induced hyperglycemia is a component of dieldrin toxicity.

Topics: Administration, Oral; Aging; Animals; Animals, Suckling; Blood Glucose; Deoxyglucose; Dieldrin; Drug Interactions; Glucose; Hyperglycemia; Lethal Dose 50; Male; Phenobarbital; Rats; Rats, Inbred Strains; Seizures

Topics: Animals; Anorexia; Dieldrin; Evoked Potentials; Hexachlorocyclohexane; Hypothermia; Limbic System; Mice; Nervous System Diseases; Rats; Seizures; Synapses; Synaptic Transmission

The concept that a challenge to a system may overcome compensatory mechanisms and thereby reveal otherwise hidden neurotoxicant-induced damage is reviewed from a neurophysiological perspective. Two broad classes of neuronal challenges, poststimulation neuronal recovery processes and epileptogenesis, are discussed in terms of their potential value for detection and characterization of neurotoxicity. Neuronal recovery studies have typically involved presentation of pairs or trains of stimuli with various interstimulus intervals. Studies involving simple (e.g., monosynaptic) systems may allow mechanistic interpretation of alterations. Paired-pulse studies involving more complex (e.g., polysynaptic sensory) systems have detected alterations more readily than other electrophysiological methods, but interpretation may not be as straightforward as the monosynaptic case. The properties of elicited seizures, as well as the threshold for production of seizures, have been used with some success for detection of neurotoxicity. Several seizure models are discussed. It is concluded that both classes of neuronal challenge hold promise for future studies of neurotoxicity.

Topics: Acrylamides; Animals; Central Nervous System; Dieldrin; Electric Stimulation; Electrophysiology; Evoked Potentials, Auditory; Evoked Potentials, Visual; Rats; Seizures; Toxicology; Trimethyltin Compounds

Topics: Animals; Behavior, Animal; Body Temperature; Chlordecone; DDT; Dieldrin; Dose-Response Relationship, Drug; Drug Interactions; Female; Insecticides; Naloxone; Nervous System Diseases; Organ Size; Rats; Rats, Inbred Strains; Seizures

Topics: Animals; Brain Chemistry; Cyclic AMP; Cyclic GMP; Dieldrin; Male; Mice; Nucleotides, Cyclic; Seizures

Topics: Animals; Behavior, Animal; Brain; Dieldrin; Dogs; Electroencephalography; Female; Hindlimb; Seizures; Species Specificity; Tremor

The onset of sustained multiple unit activity (MUA) in corticofugal axons was found to precede the onset of tonic EEG activity in 91 of 92 seizures produced by administering pentylenetetrazol, strychnine, or dieldrin to cats. Latency differences from 0-8 sec were observed with a mean of 3 sec. A trend was noted for shorter latencies with subsequent seizures in the same subject. No differences in latency were seen for spontaneous as compared to evoked seizures. Much variation was encountered in the pattern of MUA and EEG development at seizure onset. In general seizures with well-defined EEG components of desynchronization, tonic and clonic activity had the greatest latency differences and the least correspondence between MUA and EEG. Seizures with the abrupt emergence of tonic or clonic activity had the smallest latency differences and the best correspondence between MUA and EEG. Large changes in the activity along corticofugal axons were observed without EEG correlates. The evidence supports the concept that the degree of synchrony within the cortical (pyramidal) cell population is critical to the emergence and development of EEG during the tonic and clonic phases of a seizure. The data suggest that, in some cases, important changes in corticofugal output may contribute to and reinforce the activity in subcortical loci implicated in generalized seizure onset.

Topics: Action Potentials; Animals; Axons; Cats; Cerebral Cortex; Dieldrin; Electroencephalography; Male; Pentylenetetrazole; Seizures; Strychnine; Time Factors

Topics: Aldrin; Animals; Cat Diseases; Cats; Dieldrin; Female; Male; Pesticide Residues; Seizures; Soil; Soil Pollutants

Topics: Animals; Dieldrin; Electrodes, Implanted; Electroencephalography; Female; Haplorhini; Macaca mulatta; Male; Organophosphorus Compounds; Sarin; Seizures; Time Factors; Wakefulness

Topics: Animals; Cats; Cerebral Cortex; Dieldrin; Electric Stimulation; Electroencephalography; Geniculate Bodies; Male; Motor Cortex; Pyramidal Tracts; Seizures; Thalamus; Time Factors; Visual Cortex

Topics: Animals; Cats; Caudate Nucleus; Central Nervous System; Cerebellum; Cerebral Cortex; DDT; Dieldrin; Dose-Response Relationship, Drug; Electroencephalography; Hippocampus; Hydrocarbons, Halogenated; Insecticides; Male; Reticular Formation; Seizures; Superior Colliculi; Thalamus

Topics: Animals; Biological Assay; Cat Diseases; Cats; Dieldrin; Legislation, Drug; Male; Seizures; Spasm

Topics: Animals; Bird Diseases; Birds; Brain Chemistry; Chromatography, Gas; Dieldrin; Diet; Food Contamination; Insecticides; Kidney; Mercury; Mercury Poisoning; Pesticide Residues; Pesticides; Seizures; Texas

Topics: Adipose Tissue; Animals; Brain Chemistry; Dieldrin; Dose-Response Relationship, Drug; Endrin; Injections, Intravenous; Insecticides; Lethal Dose 50; Liver; Male; Mice; Mice, Inbred Strains; Motor Activity; Seizures; Time Factors

Topics: Ammonia; Animals; Brain; Bridged-Ring Compounds; Chickens; DDT; Dieldrin; Female; Glutamine; Hexachlorocyclohexane; Hydrocarbons, Halogenated; Indenes; Insecticides; Male; Rats; Seizures; Species Specificity

Topics: Animals; Central Nervous System; DDT; Dieldrin; Electroshock; Female; Injections, Subcutaneous; Intubation, Gastrointestinal; Pentobarbital; Pentylenetetrazole; Rats; Seizures; Strychnine; Time Factors

Topics: Age Factors; Animal Feed; Animals; Blood Vessels; Brain; Brain Chemistry; Brain Diseases; Brain Edema; Dieldrin; Female; Male; Poisoning; Rats; Seizures; Sex Factors; Time Factors

Topics: Accidents, Home; Adipose Tissue; Autopsy; Blood Proteins; Brain; Child, Preschool; Dieldrin; Electroencephalography; Female; Humans; Liver Function Tests; Male; Models, Biological; Muscles; Phenobarbital; Phenytoin; Protein Binding; Seizures; Time Factors

Topics: Adipose Tissue; Alkaline Phosphatase; Animals; Blood Cell Count; Blood Chemical Analysis; Blood Proteins; Body Weight; Brain Chemistry; Dieldrin; Diet; Dogs; Female; Liver; Male; Organ Size; Rats; Seizures; Sex Factors

Topics: Animals; Dieldrin; Electroencephalography; Seizures; Sheep; Visual Perception

Topics: Animals; Body Weight; Brain; Dehydration; Dieldrin; Dietary Proteins; Kidney; Liver; Male; Necrosis; Pesticides; Protein Deficiency; Rats; Regional Blood Flow; Seizures; Stress, Physiological

Topics: Animals; Chronaxy; Dieldrin; Dimethyl Sulfoxide; In Vitro Techniques; Mice; Nervous System; Pentylenetetrazole; Phenytoin; Phrenic Nerve; Rats; Seizures; Strychnine; Tetany

Topics: Animals; Body Weight; Dieldrin; Dog Diseases; Dogs; Fats; Feeding and Eating Disorders; Humans; Immobilization; Kidney; Liver; Piperazines; Seizures

Topics: Dieldrin; Electroencephalography; Humans; Insecticides; Male; Middle Aged; Seizures

Topics: Alkaloids; Dieldrin; Electroencephalography; Insecticides; Neurologic Manifestations; Occupational Diseases; Poisoning; Seizures; Toxicology

1. Increases in the concentrations of lactic acid and pyruvic acid in rat brain during acute dieldrin poisoning are associated with hyperactivity of the brain, whereas an increase in the cerebral alanine concentration occurs before the convulsions. Throughout the dieldrin-induced seizure pattern, fluctuations in the concentration of brain ammonia are out of phase with the actual convulsions. 2. Increases in the concentrations of alanine, ammonia and lactic acid in rat brain accompany picrotoxin-induced seizures; there is no increase in the concentration of glutamine. These changes are consistent with the inhibition of glutamine synthesis. 3. In addition to previously reported changes in the concentrations of intermediary metabolites of the brain after the administration of Telodrin (Hathway & Mallinson, 1964), increases have now been found in the alanine and lactic acid concentrations. Since increases in the alanine and glutamine concentrations occur before the convulsions, liberation of ammonia also occurs before the onset of convulsions and throughout their course. Ammonia-binding mechanisms later become inadequate and free ammonia accumulates in cerebral tissues. 4. An increase in the pyruvic acid concentration of the brain after the intraperitoneal injection of either dieldrin or Telodrin is endogenous in origin. 5. The parenteral administration of a small dose of glutamine increases the cerebral concentrations of alanine and glutamic acid. Some animals previously treated with glutamine resisted Telodrin convulsions. 6. Mechanisms for the disposal of ammonia liberated in brain are discussed.

Topics: Alanine; Amino Acids; Ammonia; Animals; Brain; Brain Chemistry; Central Nervous System Stimulants; Dieldrin; Furans; Glutamic Acid; Glutamine; Lactates; Metabolism; Pharmacology; Picrotoxin; Rats; Seizures

Topics: Bile; Body Fluids; Central Nervous System; Dieldrin; Feces; Fluids and Secretions; Injections, Intravenous; Intestinal Absorption; Lipid Metabolism; Metabolism; Rats; Research; Seizures; Starvation; Toxicology; Urine