Dixit Shilpi, Dhar Pushpa, Mehra Raj D
Department of Anatomy, All India Institute of Medical Sciences, New Delhi 110029, India.
Toxicol Rep. 2015 Jan 28;2:78-87. doi: 10.1016/j.toxrep.2015.01.011. eCollection 2015.
The present study focused on the role of exogenous alpha lipoic acid (ALA) in amelioration of inorganic arsenic () induced effects on apoptosis and apoptosis associated proteins in developing rat hippocampus. NaAsO (1.5/2.0 mg/kg bw) alone or along with ALA (70 mg/kg bw) was administered to rat pups (experimental groups) by intraperitoneal (i.p.) route from postnatal day (PND) 4-15. Controls received no treatment/distilled water/ALA. On PND 16, the animals were perfusion fixed and the brains were processed for paraffin embedding (CV and TUNEL staining) and cryopreservation (immunohistochemistry). The fresh brain tissue was used for Western blotting. Significant increase was observed in TUNEL positive cells and Bax (pro-apoptotic protein) expression in hippocampal sub-regions of alone treated groups, whereas Bcl-2 expression was intensified in animals receiving ALA with . Densitometric analysis (Western blots) revealed optimal restoration of Bax and Bcl-2 ratio in animals receiving ALA with , thereby suggesting the protective role of ALA in induced developmental neurotoxicity.
本研究聚焦于外源性α-硫辛酸（ALA）在改善无机砷（）对发育中大鼠海马体凋亡及凋亡相关蛋白影响方面的作用。从出生后第4天至第15天，通过腹腔注射（i.p.）途径，将NaAsO（1.5/2.0 mg/kg体重）单独或与ALA（70 mg/kg体重）一起给予幼鼠（实验组）。对照组不接受任何处理/蒸馏水/ALA。在出生后第16天，对动物进行灌注固定，然后将大脑进行石蜡包埋处理（用于苏木精-伊红染色和TUNEL染色）以及冷冻保存（用于免疫组织化学）。新鲜脑组织用于蛋白质印迹分析。在仅接受处理的组的海马亚区中，观察到TUNEL阳性细胞和Bax（促凋亡蛋白）表达显著增加，而在接受ALA与 共同处理的动物中，Bcl-2表达增强。光密度分析（蛋白质印迹）显示，接受ALA与 共同处理的动物中Bax和Bcl-2比例得到最佳恢复，从而表明ALA在 诱导的发育性神经毒性中具有保护作用。
