Glucose feeding exacerbates parathion-induced neurotoxicity.
Glucose feeding exacerbates parathion-induced neurotoxicity.
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葡萄糖喂养会加剧对硫磷引起的神经毒性。
DOI：
10.1080/15287390151143659
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Pope,CN
中科院分区：
文献类型：
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作者：
Olivier,K;Liu,J;Karanth,S;Zhang,H;Roane,DS;Pope,CN
过量的糖类摄入会改变多种生物转化过程以及多种外源物质的药理和毒理特性。本文研究了补充葡萄糖对有机磷农药对硫磷(PS)及其活性代谢物乙酰胆碱酯酶(AChE)抑制剂对氧磷(PO)神经毒性的影响。实验组(n=6-12)在染毒前7d开始自由饮用自来水或自来水中15%葡萄糖(w/v)。每天测量食物、卡路里摄入量和体重。动物接受PS(4.5、9或18 mg/kg，sc)或PO(0.3、0.5或0.7 mg/kg，sc)的刺激，并在接下来的13d每天记录神经毒性的临床体征(即自主神经功能障碍、不自主运动)。与OP暴露前7d相比，葡萄糖摄入量显著下降(~50%)，总热量消耗增加(~20%)。与PS暴露相关的功能毒性在葡萄糖喂养的大鼠(GF)中增加，但葡萄糖饮食对PO治疗后的毒性临床症状没有明显影响。低剂量(4.5 mg/kg和9 mg/kg)葡萄糖喂养可增加PS处理后3d额叶皮质和血浆中AChE的抑制程度。时程研究(PS暴露后3、7和11d，18 mg/kg，sc)表明，在较晚的时间点，服用葡萄糖的动物的脑和血浆AChE抑制显著增强。反之，给予葡萄糖对PO暴露后AChE的抑制程度没有影响。饲喂葡萄糖对肝脏微粒体PS氧化脱硫率、肝脏或血浆对氧磷酶活性、肝脏或血浆羧酸酯酶活性均无显著影响。PS(18 mg/kg，sc)暴露7d后，GF大鼠的M受体下调幅度更大。据推测，过量的葡萄糖摄入减少了其他饮食成分的摄取，特别是氨基酸，限制了AChE的从头合成，从而恢复了突触传递。由于PO暴露后的抑制持续时间较短，在功能恢复过程中，AChE的自发激活可能比从头合成蛋白更重要，因此葡萄糖喂养对其毒性的影响可能更重要。从糖中摄取大部分卡路里的人，可能会面临更高的有机磷杀虫剂(如PS)急性毒性风险。
Excessive dietary intake of sugars could alter various biotransformation processes and the pharmacological and toxicological properties of numerous xenobiotics. In the present study, the effects of glucose supplementation were examined on the neurotoxicity of the organophosphorus (OP) pesticide parathion (PS) and its active metabolite, paraoxon (PO), a potent inhibitor of acetylcholinesterase (AChE). Rats (n= 6-12/treatment group) were given free access to tap water or 15% glucose (w/v) in tap water beginning 7 d prior to OP toxicant exposure. Food, caloric intake, and body weight were measured daily. Animals were challenged with either PS (4.5, 9, or 18 mg/kg, sc) or PO (0.3, 0.5, or 0.7 mg/kg, sc) and clinical signs of neurotoxicity (i.e., autonomic dysfunction, involuntary movements) were recorded daily for the following 13 d. Glucose feeding was associated with a dramatic drop (~50%) in feed intake and an increase (~20%) in total caloric consumption over the 7 d prior to OP exposure. Functional toxicity associated with PS exposure was increased in glucose-fed (GF) rats, but the glucose diet had no apparent effect on clinical signs of toxicity following PO treatment. Glucose feeding increased the magnitude of AChE inhibition in the frontal cortex and plasma at lower dosages (i.e., 4.5 and 9 mg/kg) 3 d following PS treatment. Time-course studies (3, 7, and 11 d after PS exposure, 18 mg/kg, sc) indicated significantly greater brain and plasma AChE inhibition in glucosefed animals at later time points. In contrast, glucose feeding had no effect on the degree of AChE inhibition following PO exposure. Neither liver microsomal oxidative desulfuration of PS, nor liver or plasma paraoxonase, nor liver or plasma carboxylesterase activities were measurably affected by glucose feeding. Downregulation of muscarinic receptors 7 d after PS exposure (18 mg/kg, sc) was more extensive in GF rats. It is postulated that excessive glucose consumption decreases the intake of other dietary components, in particular amino acids, limiting the de novo synthesis of AChE and consequent recovery of synaptic transmission. Due to the shorter duration of inhibition following PO exposure, spontaneous reactivation of AChE may be more important than de novo protein synthesis in recovery of function, and thus with the effects of glucose feeding on its toxicity. Individuals that derive a large proportion of their calories from sugars may be at higher risk of acute toxicity from organophosphorus pesticides such as PS.