This elevation in brain levels of Glu and GABA can be explained by one or more of the following mechanisms: neural damage induced by DM as previously reported by Groose . (2002); neurological signs and symptoms that characterize moderate hypoglycemia seen in the present study in DM group () and as confirmed by previous studies using other insecticides (Srivastava and Singh, 1981; Enan ., 1982; Agrawal ., 1987; Rajini and Krishnakumari, 1988; Bendahou ., 1999); the utilization of s like glutamate and glutamine as alternative energy sources in moderate hypoglycemia as supported by preliminary reports of Butterworth (1983) and Butcher . (1987), who studied the adverse effect of hypoglycemia on the synthesis of the neurotransmitters, GABA and glutamate. They revealed that hypoglycemia produces a substantial increase in extracellular concentrations of glutamate and GABA. It has also been suggested that pyrethroid, especially deltamethrin, can disturb the function of brain tissue in high-affinity-glutamate uptake with their alpha-cyano-group which could play an important role in cerebral stimulation in mammals (Zhao ., 1997). Recently, Wu and Liu (2003) reported that, deltamethrin induces neurodegeneration via a glutamate dependent pathway.
Deltamethrin powder (purity, 98.9%) was administered orally in gelatine capsules to groups of beagles aged about 26 weeks at a dose of 0, 2, 10, or 50 mg/kg bw per day for 13 weeks. Six animals of each sex received 0 or 50 mg/kg bw per day, and three of each sex were kept for a 4-week recovery period; three animals of each sex received 2 or 10 mg/kg bw per day. There were no deaths. Most animals at the highest dose showed evidence of neurological disturbance, with intermittent unsteady gait (mainly hind gait), which in some cases prevented the animals from standing. These signs were associated with body tremors. During weeks 1–6, animals at the highest dose showed an increased frequency of vomiting and, in a few dogs, salivation, shaking of the head, chewing of the extremities, and hunched posture. Reduced body-weight gain, mainly in males, and reduced food intake were seen, indicating that 50 mg/kg bw per day was close to the maximum tolerated dose. However, no treatment-related clinical signs were observed during the recovery period, indicating their reversibility after cessation of dosing, and food intake returned to normal during that period. The lack of any clear dose–response relationship in weight gain among females indicates that these changes had anuncertain association with treatment, and it was concluded that a clear effect oftreatment on weight gain was confined to males at 50 mg/kg bw per day. No treatment-related clinical signs were observed at 2 or 10 mg/kg bw per day. No treatment-related changes were found at any dose by ophthalmoscopy, extensive neurological examinations (cranial nerves, segmental and postural reflexes, behaviour, and muscle tonicity), haematology, blood chemistry, or terminal studies. The NOAEL was 10 mg/kg bw per day on the basis of neurological disturbances and reduced food intake and body-weight gain at 50 mg/kg bw per day (Ryle et al., 1991b).
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The present data have also exposed a significant reduction in brain level of DA in DM group at the 3rd week and in DMA group at the 1st week which might be attributed to inhibited DA synthesis as supported by the recent work of Liu . (2006). According to the authors, the contents of DA metabolites DOPAC and HVA were increased in striatum after deltamethrin administration, indicating a stimulated dopamine turnover and inhibited DA synthesis. The authors claimed a novel aspect of deltamethrin neurotoxicity and suggested tyrosine hydroxylase as a molecular target of deltamethin on dopamine metabolism in the nigrostriatal pathway. The findings of Bloomquist (2002) that oxidative damage induced by pyrethroid insecticides, especially deltamethrin, possess specific effects on striatal dopaminergic neurotransmission particularly the substantia nigra might support this idea.
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Deltamethrin powder (purity, 98.9%) was administered orally in gelatine capsules to groups of four male and four female 23–24-week-old beagles at a dose of 0, 1, 10, or 50 mg/kg bw per day for 1 year. There were no deaths. The clinical signs, seen only at the two higher doses, were chewing and scratching of the extremities, abnormal gait, tremors, and liquid faeces. These signs were accompanied by locomotor impairment, and at the highest dose the scratching resulted in lesions on the tail, paws, and scapular regions which necessitated veterinary treatment. Chewing and scratching of the extremities was also noted in two dogs at the lowest dose but also in a few control animals; consequently, this behaviour was not attributed to treatment at that dose. The locomotor effects, clearly observed at the two higher doses, consisted of unsteadiness, incoordination of hindlimb gait, and, sometimes, splaying of the limbs and/or digits. Such effects were also seen in association with body tremors and abnormal movements of the head. None of the animals at 1 mg/kg bw per day showed these neurological signs.
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Deltamethrin (purity, 100%) dissolved in PEG 200 was administered orally in gelatine capsules to groups of two 25-week-old beagle dogs of each sex at a dose of 0 or 0.1 mg/kg bw per day and to groups of five animals of each sex at a dose of 1, 2.5, or 10 mg/kg bw per day for 13 weeks. There were no deaths. At the highest dose, unsteadiness, body tremors, and jerking movements were seen, particularly in males, in weeks 2, 3, and 4, but these signs diminished markedly in both incidence and severity during weeks 5–9 and were then seen in only one dog during week 13. Vomiting was observed in all groups, including the controls, but was significantly more frequent in animals at the highest dose during the first week of treatment. This group also showed excessive salivation at the beginning of the experiment, which diminished during treatment. Liquid faeces were found in all treated groups throughout treatment but were much more frequent at the two higher doses. Dilatation of the pupils was seen 4–7 h after treatment at these doses, which persisted throughout the day. During the first 2 weeks of treatment, both males and females receiving 10 mg/kg bw per day gained significantly less weight than the controls (males: controls, 830 g, high dose, –20 g,