Protective Effects of N-Acetylcysteine on Dipentyl Phthalate Induced Cognitive Dysfunction and Brain Oxidative Stress in Mice

S. Gautam, S. Jain, Proteesh Rana, B. Banerjee, Pramod Kumari
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Abstract

Background: Dipentyl phthalate (DPeP) is a plasticizer compound commonly used in polyvinylchloride plastic to enhance softness and flexibility. They are not bound covalently to plastic polymers; therefore, they can dissolve into the environment and adversely affect the health of humans and animals. Objectives: The aim of this study was to investigate the effect of DPeP on cognition and protective effects of N-acetylcysteine (NAC) on DPeP induced alteration in cognitive behaviour and oxidative stress markers in mice. Methods: Mice were orally treated with 2 doses (33 mg/kg and 100 mg/kg) of DPeP for 28 days. Cognitive functions were assessed using spatial navigation tasks on the Morris water maze and the step-down latency in the passive avoidance apparatus. Oxidative stress was assessed by examining the levels of malondialdehyde, glutathione, ferric reducing antioxidant power, and 8-hydroxy-deoxyguanosine levels in the whole brain of mice. Results: There was a significant increase in latency in spatial navigation tasks and a significant decline in the step-down latency in passive avoidance apparatus in the DPeP-treated group compared to the control groups. There was also a significant increase in the levels of oxidative stress following DPeP administration as seen with the rise in the levels of malondialdehyde, 8-hydroxy-deoxyguanosine, and a fall in glutathione and ferric reducing antioxidant power levels. Conclusion: The present study demonstrated that DPeP adversely affects learning and memory functions in mice by oxidative stress-mediated neuronal damage. These effects were attenuated by pretreatment with N-acetylcysteine.
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n -乙酰半胱氨酸对邻苯二甲酸二戊酯诱导的小鼠认知功能障碍和脑氧化应激的保护作用
背景:邻苯二甲酸二戊酯(DPeP)是一种增塑剂化合物,通常用于聚氯乙烯塑料,以提高柔软性和柔韧性。它们不与塑料聚合物共价结合;因此,它们可以溶解到环境中,对人类和动物的健康产生不利影响。目的:探讨DPeP对小鼠认知功能的影响及n -乙酰半胱氨酸(NAC)对DPeP诱导小鼠认知行为和氧化应激标志物改变的保护作用。方法:小鼠口服2剂量(33 mg/kg、100 mg/kg) DPeP 28 d。通过Morris水迷宫的空间导航任务和被动回避装置的降压延迟来评估认知功能。通过检测小鼠全脑丙二醛、谷胱甘肽、铁还原抗氧化能力和8-羟基脱氧鸟苷水平来评估氧化应激。结果:与对照组相比,dpep治疗组空间导航任务潜伏期显著增加,被动回避装置降压潜伏期显著降低。在服用DPeP后,氧化应激水平也显著增加,丙二醛、8-羟基脱氧鸟苷水平上升,谷胱甘肽和铁的抗氧化能力水平下降。结论:本研究表明,DPeP通过氧化应激介导的神经元损伤对小鼠的学习记忆功能产生不利影响。用n -乙酰半胱氨酸预处理后,这些影响减弱。
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