Department of Pharmacology, University College of Medical Sciences, University of Delhi, Delhi 110095, India.
Fundam Clin Pharmacol. 2013 Apr;27(2):146-51. doi: 10.1111/j.1472-8206.2011.00977.x. Epub 2011 Jul 26.
Melatonin is an important modulator of nervous system functioning and important neural antioxidant. Organophosphate pesticides like phosphamidon (PHOS) have been shown to adversely affect memory and induce oxidative stress on both acute and chronic exposure. This study was designed to explore the modulation of the effects of PHOS on cognitive function by melatonin (MEL). Cognitive function was assessed using step-down latency (SDL) on a passive avoidance apparatus and transfer latency (TL) on an elevated plus maze. Oxidative stress was assessed by examining the levels of malondialdehyde (MDA) and nonprotein thiols (NP-SH) in isolated homogenized whole brain samples. The results showed a significant reduction in SDL and prolongation of TL in the PHOS (1.74 mg/kg/day; p.o.)-treated group at weeks 6 and 8 as compared to the control group. Two-week treatment with MEL (5 mg/kg/day; i.p.) antagonized the effect of PHOS on SDL as well as TL. PHOS alone produced a significant increase in the brain MDA levels and decrease in the brain NP-SH levels. Treatment with MEL attenuated the effect of PHOS on oxidative stress. Together the results showed that MEL attenuated the cognitive dysfunction and decreased oxidative stress induced by PHOS in the brain.
褪黑素是神经系统功能的重要调节剂，也是重要的神经抗氧化剂。有机磷农药如磷酰胺（PHOS）已被证明会对记忆产生不利影响，并在急性和慢性暴露时引起氧化应激。本研究旨在探讨褪黑素（MEL）对 PHOS 对认知功能影响的调节作用。使用被动回避装置的步下潜伏期（SDL）和高架十字迷宫的转移潜伏期（TL）评估认知功能。通过检查分离的匀浆全脑样本中的丙二醛（MDA）和非蛋白巯基（NP-SH）水平来评估氧化应激。结果显示，与对照组相比，PHOS（1.74 mg/kg/天；口服）治疗组在第 6 周和第 8 周时 SDL 显著降低，TL 延长。MEL（5 mg/kg/天；腹腔内注射）两周治疗可拮抗 PHOS 对 SDL 以及 TL 的作用。PHOS 单独使用会导致大脑 MDA 水平升高和 NP-SH 水平降低。MEL 治疗可减轻 PHOS 对氧化应激的影响。结果表明，MEL 可减轻 PHOS 引起的大脑认知功能障碍和氧化应激。
