کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2570956 | 1561181 | 2007 | 9 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Neuronal oxidative injury and dendritic damage induced by carbofuran: Protection by memantine Neuronal oxidative injury and dendritic damage induced by carbofuran: Protection by memantine](/preview/png/2570956.png)
Carbamate insecticides mediate their neurotoxicity by acetylcholinesterase (AChE) inactivation. Male Sprague–Dawley rats acutely intoxicated with the carbamate insecticide carbofuran (1.5 mg/kg, sc) developed hypercholinergic signs within 5–7 min of exposure, with maximal severity characterized by seizures within 30–60 min, lasting for about 2 h. At the time of peak severity, compared with controls, AChE was maximally inhibited (by 82–90%), radical oxygen species (ROS) markers (F2-isoprostanes, F2-IsoPs; and F4-neuroprostanes, F4-NeuroPs) were elevated 2- to 3-fold, and the radical nitrogen species (RNS) marker citrulline was elevated 4- to 8-fold in discrete brain regions (cortex, amygdala, and hippocampus). In addition, levels of high-energy phosphates (HEPs) were significantly reduced (ATP, by 43–56%; and phosphocreatine, by 37–48%). Values of total adenine nucleotides and total creatine compounds declined markedly (by 41–56% and 35–45%, respectively), while energy charge potential remained unchanged. Quantitative morphometric analysis of pyramidal neurons of the hippocampal CA1 region revealed significant decreases in dendritic lengths (by 64%) and spine density (by 60%). Pretreatment with the N-methyl-d-aspartate (NMDA) receptor antagonist memantine (18 mg/kg, sc), in combination with atropine sulfate (16 mg/kg, sc), significantly attenuated carbofuran-induced changes in AChE activity and levels of F2-IsoPs and F4-NeuroPs, declines in HEPs, as well as the alterations in morphology of hippocampal neurons. MEM and ATS pretreatment also protected rats from carbofuran-induced hypercholinergic behavioral activity, including seizures. These findings support the involvement of ROS and RNS in seizure-induced neuronal injury and suggest that memantine by preventing carbofuran-induced neuronal hyperactivity blocks pathways associated with oxidative damage in neurons.
Journal: Toxicology and Applied Pharmacology - Volume 219, Issues 2–3, March 2007, Pages 97–105