Environmental Biochemistry and Molecular Biology Laboratory, Department of Biochemistry, University College of Medical Sciences and GTB Hospital (University of Delhi), Dilshad Garden, Delhi, 110095, India.
Neurochem Res. 2013 Oct;38(10):2136-47. doi: 10.1007/s11064-013-1122-0. Epub 2013 Aug 15.
Triazophos, O,O-diethyl-1-H-1,2,4-triazol-3-yl phosphorothioate, (TZ) is an organophosphate pesticide widely used as an insecticide in agriculture fields, however, its adverse effects on cognitive function remain unknown till date. The present study was designed to identify the effect of TZ on cognitive function in order to gain an insight into the molecular mechanism(s) probably involved in TZ induced toxicity. Wistar male albino rats were orally administered with TZ at 8.2 mg/kg bw daily for 30 days. Cognitive function was assessed by evaluating step down latency (SDL) in passive avoidance apparatus, transfer latency (TL) on elevated plus maze and escape latency (EL) using morris water maze. The biochemical changes, in terms of malondialdehyde (MDA), reduced glutathione (GSH) and brain derived neurotrophic factor (BDNF) levels were evaluated in hippocampi regions. Relative mRNA expression and protein expression of BDNF were also evaluated. The results demonstrated that rats treated with TZ showed significantly (p < 0.01) reduced SDL and prolonged TL and EL as compared to control group rats. Moreover, significantly low (p < 0.01) mRNA expression and protein levels (p < 0.001) of BDNF, increased MDA and reduced GSH levels were observed in TZ treated rats. The study concludes that chronic exposure to TZ significantly impairs the learning and memory which may be attributed to the significantly reduced mRNA and protein expression of BDNF in hippocampus. Moreover, BDNF is negatively correlated to MDA levels and positively correlated to GSH levels. Hence, it can be suggested that interplay between BDNF and oxidative stress plays an important role in mediating the toxic effects of TZ.
三唑磷，O,O-二乙基-1-H-1,2,4-三唑-3-基硫代磷酸酯（TZ）是一种广泛用作农业领域杀虫剂的有机磷农药，但它对认知功能的不良影响至今仍不清楚。本研究旨在确定 TZ 对认知功能的影响，以便深入了解可能涉及 TZ 诱导毒性的分子机制。雄性 Wistar 白化大鼠每天口服 TZ 剂量为 8.2mg/kg bw，共 30 天。通过评估被动回避装置中的步下潜伏期（SDL）、高架十字迷宫中的转移潜伏期（TL）和 Morris 水迷宫中的逃避潜伏期（EL）来评估认知功能。在海马区评估生化变化，包括丙二醛（MDA）、还原型谷胱甘肽（GSH）和脑源性神经营养因子（BDNF）水平。还评估了 BDNF 的相对 mRNA 表达和蛋白表达。结果表明，与对照组大鼠相比，TZ 处理的大鼠 SDL 明显降低（p<0.01），TL 和 EL 延长。此外，在 TZ 处理的大鼠中，BDNF 的 mRNA 表达和蛋白水平显著降低（p<0.01），MDA 水平升高，GSH 水平降低。研究结论是，慢性暴露于 TZ 会显著损害学习和记忆能力，这可能归因于海马体中 BDNF 的 mRNA 和蛋白表达显著降低。此外，BDNF 与 MDA 水平呈负相关，与 GSH 水平呈正相关。因此，可以认为 BDNF 和氧化应激之间的相互作用在介导 TZ 的毒性作用中起着重要作用。
