Department of Chemistry, Missouri University of Science and Technology, Rolla, MO 65409, USA.
Hum Exp Toxicol. 2012 Sep;31(9):931-44. doi: 10.1177/0960327112438287. Epub 2012 Feb 21.
Methamphetamine (METH), a highly addictive drug used worldwide, induces oxidative stress in various animal organs, especially the brain. This study evaluated oxidative damage caused by METH to tissues in CD-1 mice and identified a therapeutic drug that could protect against METH-induced toxicity. Male CD-1 mice were pretreated with a novel thiol antioxidant, N-acetylcysteine amide (NACA, 250 mg/kg body weight) or saline. Following this, METH (10 mg/kg body weight) or saline intraperitoneal injections were administered every 2 h over an 8-h period. Animals were killed 24 h after the last exposure. NACA-treated animals exposed to METH experienced significantly lower oxidative stress in their kidneys, livers, and brains than the untreated group, as indicated by their levels of glutathione, malondialdehyde, and protein carbonyl and their catalase and glutathione peroxidase activity. This suggests that METH induces oxidative stress in various organs and that a combination of NACA as a neuro- or tissue-protective agent, in conjunction with current treatment, might effectively treat METH abusers.
甲基苯丙胺（METH）是一种在世界范围内广泛使用的高度成瘾性药物，会在各种动物器官（尤其是大脑）中引起氧化应激。本研究评估了 METH 对 CD-1 小鼠组织造成的氧化损伤，并确定了一种可能对抗 METH 诱导毒性的治疗药物。雄性 CD-1 小鼠先用新型硫醇抗氧化剂 N-乙酰半胱氨酸酰胺（NACA，250mg/kg 体重）或生理盐水预处理。之后，每隔 2 小时给 METH（10mg/kg 体重）或生理盐水腹腔注射，共 8 小时。最后一次暴露后 24 小时处死动物。与未处理组相比，接受 METH 注射的 NACA 处理动物的肾脏、肝脏和大脑中的氧化应激水平明显较低，这表明其谷胱甘肽、丙二醛、蛋白质羰基和过氧化氢酶及谷胱甘肽过氧化物酶的活性较低。这表明 METH 会在各种器官中引起氧化应激，而将 NACA 作为神经或组织保护剂与当前的治疗方法相结合，可能会有效地治疗 METH 滥用者。
