Perturbed Synaptosomal Calcium Homeostasis and Behavioral Deficits Following Carbofuran Exposure: Neuroprotection by <Emphasis Type="Italic">N</Emphasis>-Acetylcysteine |
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Authors: | Amit Kamboj Rajat Sandhir |
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Institution: | (1) Department of Biochemistry, Basic Medical Science Building, Panjab University, Chandigarh, 160014, India |
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Abstract: | The protective effects of N-acetylcysteine (NAC) on carbofuran-induced alterations in calcium homeostasis and neurobehavioral functions were investigated
in rats. Rats were exposed to carbofuran at a dose of 1 mg/kg body weight, orally for a period of 28 days. A significant decrease
in Ca2+ATPase activity was observed following carbofuran exposure with a concomitant increase in K+-induced 45Ca2+ uptake through voltage operated calcium channels. This was accompanied with a marked accumulation of intracellular free calcium
in synaptosomes. The increase in intracellular calcium levels were associated with an increased lipid peroxidation and decreased
glutathione content in carbofuran exposed animals. NAC administration (200 mg/kg body weight, orally) to the carbofuran exposed
animals had a beneficial effect on carbofuran-induced alterations in calcium homeostasis and resulted in repletion in glutathione
levels and resulted in lowering the extent of lipid peroxidation. Marked impairment in the motor functions were seen following
carbofuran exposure, which were evident by the significant decrease in the locomotor activity and reduction in the retention
time of the rats on rotating rods. Cognitive deficits were also seen as indicated by the significant decrease in active and
passive avoidance response. NAC treatment, on the other hand, protected the animals against carbofuran-induced neurobehavioral
deficits. The results support the hypothesis that carbofuran exerts its toxic effects by disrupting calcium homeostasis, which
may have serious consequences on neuronal functioning, and clearly show the potential beneficial effects of N-acetylcysteine on carbofuran induced alterations in synaptosomal calcium homeostasis. |
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Keywords: | Carbofuran N-acetylcysteine Ca2+-ATPase Voltage operated calcium channels Intracellular Ca2+ Brain |
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