M. Anand

Role of Gaba Receptor Complex in Low Dose Lindane (HCH) Induced Neurotoxicity: Neurobehavioural, Neurochemical and Electrophysiological Studies

Lindane is widely used as an insecticide and scabicide in mammals. High doses in chronic exposures caused hyperexcitability and convulsions and impaired motor activity involving GABA-ergic mechanism. To investigate the role of GABA/Benzodiazepine mechanism in the neurotoxicity of low doses of lindane, rats were administered 2, 3, or 5 mg/kg orally for 90 days and behavioural, electrophysiological, and neurochemical studies were conducted. The animals exposed to lindane exhibited increased geotaxis and decreased spontaneous drug-induced locomotor activity (which further potentiated by phenobarbitone and increased after leptazol). The EEG of the treated rats showed high voltage slow-wave activity (HVSA) patterns with occasional spindles (9-10 HZ-amplitude of 100 uv). A significant increase (p < 0.01) in GABA levels in cerebellum and significant increase in benzodiazepine receptors in cerebellar membrane measured by (3H)flunitrazepam binding were observed in the animals exposed to 3 and 5 mg lindane. The study suggests that low dose chronic exposure of lindane causes neurobehavioral, neurochemical, and electrophysiological effects involving GABA-ergic mechanism(s).

Cardiotoxicity and hypertension in rats after oral lead exposure.

The rats were exposed to lead (0.25, 0.5 and 1.0 per cent lead acetate through drinking water) for 90 days to study its effect on some physiological and morphological parameters of the cardiovascular system. Blood lead levels increased in a dose dependent manner but heart tissue showed rise at only two higher doses in exposed animals. The two higher doses of lead resulted in an increased arterial blood pressure and calcium influx in atrial trabeculae and papillary muscles. No marked pathological or histochemical changes were observed in heart tissue excepting congestion and slightly reduced activity of succinic dehydrogenase in the highest dosed group. It was concluded that lead exposure through drinking water may produce increased arterial blood pressure and minor changes in the myocardium. Whether these changes are mediated through the effect of lead on the calcium transport needs further investigation.

Role of neurotransmitters in fenitrothion-induced aggressive behaviour in normal and lesioned rats

Normal and brain-lesioned (amygdala, septal and nigral regions) rats exposed to fenitrothion (10 mg/kg) for 15 subsequent days showed elevated foot-shock fighting behaviour (septal and nigral lesioned rats). Treated animals failed to perform the rotorod test and showed decreased locomotor activity followed by convulsions. The brain-lesioned rats treated with 10 mg/kg fenitrothion showed a marked decrease in the level of norepinephrine (NE) and serotonin (5-HT).

Endosulfan and cholinergic (muscarinic) transmission: Effect on electroencephalograms and [3H]quinuclidinyl benzilate in pigeon brain

Single exposure of endosulfan (5 mg/kg) to pigeons (Columbia livia) caused neuronal hyperexcitability as evidenced by spike discharges of 200-500 microV in the electroencephalograms (EEG) from the telencephalon and hyperstriatum, but there was no effect on the ectostriatal area. Cholinergic (muscarinic) receptor binding study using [3H]quinuclidinyl benzilate ([3H]QNB) as a specific ligand indicated that a single exposure to 5 mg/kg of endosulfan caused a significant increase (P less than 0.05) in [3H]QNB binding to the striatal membrane. Behavioral study further indicated that a single dose of 200 micrograms/kg of oxotremorine produced a significant induction in the tremor (P less than 0.01) in endosulfan-pretreated pigeons. The results of this behavioral and biochemical study indicate the involvement of a cholinergic (muscarinic) transmitter system in endosulfan-induced neurotoxicity.

Effects of the level of dietary protein on the toxicity of hexachlorocyclohexane in rats

Male albino rats were fed for 28 days from weaning on diets containing 5% (group 1), 10% (group 2) and 21% (group 3, normal protein) protein as casein. At the end of dietary period, HCH was administered daily for 30 days to investigate the interaction between protein deficiency and pesticide toxicity. The results indicated that rats fed a lower protein diet and HCH had a higher mortality, lower rate of growth, increased liver weight and deposition of the pesticide in blood and tissues in larger amounts. Blood pressure (systolic and diastolic) was significantly increased and the heart rate showed tachycardia in low protein exposed animals. A significant increase of total lipids, cholesterol, triglycirides, free fatty acids in serum and tissues of animals exposed to low protein was observed. A close correlation existed between lipid accumulation and storage of HCH in tissues and dietary protein seemed to play an important role in detoxification.

Pulmonary biochemical assessment of fenitrothion toxicity in rats

Study of alterations in the bronchoalveolar lavage fluid and lipid peroxidation of lung mitochondria

Lindane-induced changes in glucose and glutathione levels in cats

Cats were given lindane (1 and 2 mg/kg i.v.) and the levels of glucose in blood and glutathione in blood and liver were measured at 30 min, 1, 2, 4 and 8 h. The results showed a sharp decrease in blood glutathione at an early interval with subsequent recovery, whereas there was no change in liver up to 2 h followed by a significant decrease at later intervals with no sign of recovery. The pesticide also showed a hypoglycemic effect at all intervals.

Some Neurotoxicological consequences of Hexachlorocyclohexane (HCH) stress in rats fed on protein deficient diet

Hexachlorocyclohexane (HCH), an organochlorinated pesticide used extensively for the protection of crops, has been reported to affect the central nervous system. Attempts have been made to validate the behavioural changes including distance travelled, time resting, stereotypic time, ambulatory time, stereotypic movements and vertical movements in rats treated with HCH (50 mg/kg) and fed on protein deficient diet (5% Casein) for 120 days. Significant (P < 0.001) increase of 5‐HT uptake by platelets was recorded in pesticide exposed animals. Similarly ADP induced aggregatory responses were found to be enhanced significantly (P < 0.001). Bioaccumulation of pesticide in vital organs suggest that insecticide circulate rapidly through the body and can have a rapid and definitive effect. Changes in behaviour and platelets function may also be claimed to the promising sign of neurotoxicity occurring at the lower level of pesticide exposure under the influence of malnutrition.

Changes in cardiac rhythm and calcium levels in guinea pigs treated chronically with fenitrothion

Fenitrothion, an acetylcholinesterase inhibitor, causes bradycardia following long‐term exposure. To analyse the mechanism underlying these cardiac changes, ginea pigs were exposed to fenitrothion 5 and 10 mg/kg for 30 consecutive days. Electrocardiogram (ECG) showed increase in PR and RR intervals. These changes were more prominent in the animals receiving 10 mg/kg fenitrothion which occasionally showed extrasystoles. In isolated atria preparation heart rate was decreased at higher dose. Amplitude of cardiac rhythm decreased with respect to increased ACh concentration. Hypocalcemia was recorded in fenitrothion‐treated animals. The residual content of fenitrothion was increased in both groups of animals following a pattern: brain> spleen> heart> liver> kidney.

Distribution of lindane in plasma and brain after a single administration to cats

The distribution of lindane and its metabolites in the plasma and brain of the cats after 30 minutes, 1, 2, 4 and 8 hours of administration of lindane (2mg/kg, i.v.) was investigated. The compound distributes differentially in the CNS and this pattern changes with time. The pattern of distribution shows that although lindane concentration is higher in areas with a high myelin content, it disappears more rapidly from gray matter. The plasma levels were also high at 30 minutes interval and then gradually decreased. The rate of formation of the metabolite 2,4,6‐Trichlorophenol appeared to be maximum in the first 4 hours. The accumulation of the compound and its metabolite in brain during the experimental period was not evident.