Karp Jonathan D, Szczytkowski Jennifer L, Gentile Christopher F
Department of Biology, Rider University, 2083 Lawrenceville Road, Lawrenceville, NJ 08648, USA.
Life Sci. 2004 Sep 10;75(17):2077-89. doi: 10.1016/j.lfs.2004.04.020.
To determine if the chemotherapeutic drug cyclophosphamide influences the activity of the sympathetic nervous system, the effects of cyclophosphamide on norepinephrine concentration in the heart, adrenal gland, spleen, and thymus gland were evaluated. Male BALB/cByJ mice were administered a single injection of cyclophosphamide (15, 50, or 100 mg/kg, i.p) or saline-vehicle. Organs were collected 72 or 120 h after injection and norepinephrine concentrations were determined by high pressure liquid chromatography with electrochemical detection. Cyclophosphamide reduced spleen, thymus gland, and heart mass while also elevating spleen and thymus gland norepinephrine concentrations (both pmoles/mg tissue and pmoles/mg protein) in a dose- and time-dependent manner. Norepinephrine concentrations in heart and adrenal gland were not altered by cyclophosphamide at any drug dose or time point. Dose- and time-dependent cyclophosphamide-mediated changes in peripheral norepinephrine levels in the spleen and thymus gland are interesting because subjects administered cyclophosphamide may be more susceptible to opportunistic infections, not only because the drug is antineoplastic, but also because the drug alters nervous system-immune system communication and the neurochemical milieu in which surviving cells interact.
为了确定化疗药物环磷酰胺是否会影响交感神经系统的活性，评估了环磷酰胺对心脏、肾上腺、脾脏和胸腺中去甲肾上腺素浓度的影响。给雄性BALB/cByJ小鼠单次注射环磷酰胺（15、50或100mg/kg，腹腔注射）或生理盐水。在注射后72或120小时收集器官，并用高压液相色谱电化学检测法测定去甲肾上腺素浓度。环磷酰胺降低了脾脏、胸腺和心脏的重量，同时还以剂量和时间依赖性方式提高了脾脏和胸腺中的去甲肾上腺素浓度（以每毫克组织和每毫克蛋白质中的皮摩尔数计）。在任何药物剂量或时间点，环磷酰胺均未改变心脏和肾上腺中的去甲肾上腺素浓度。环磷酰胺介导的脾脏和胸腺中外周去甲肾上腺素水平的剂量和时间依赖性变化很有趣，因为接受环磷酰胺治疗的受试者可能更容易受到机会性感染，这不仅是因为该药物具有抗肿瘤作用，还因为该药物会改变神经系统与免疫系统之间的通讯以及存活细胞相互作用的神经化学环境。
