Schultze A Eric, Konrad Robert J, Credille Kelly M, Lu Quynh Anh, Todd John
Department of Pathology, Lilly Research Laboratories, Greenfield, Indiana 46140, USA.
Toxicol Pathol. 2008 Oct;36(6):777-82. doi: 10.1177/0192623308322016. Epub 2008 Jul 22.
Serum cardiac troponin-I (cTnI) has been validated as a biomarker for cardiotoxicity in numerous animal models; however, owing to sensitivity issues cTnI concentrations in healthy, resting animals used in toxicology studies have not been established. Serum from healthy and isoproterenol hydrochloride (iso)-treated rats, dogs, and monkeys were assayed using the Erenna system. The Erenna cTnI assay provided sensitivity < 1 ng/L across human, rat, dog, and monkey cTnI. Linear responses (R(2)= 0.99) were observed for all species. Precision studies yielded interassay CVs of curve fit quantification from 2% to 4% between 1.6 and 5000 ng/L, and 23% at 0.78 ng/L. Strong correlation (R(2)= 0.99) was obtained between Erenna and Beckman Access cTnI. Concentrations of cTnI in healthy animals ranged from 1 to 9 ng/L. In longitudinal studies of iso-treated animals, the concentrations of cTnI in the control vehicle-treated groups were 10-20 ng/L for rats (N = 10) and predose values of 2-3 ng/L for dogs (N = 3). Measured with the Erenna assay system, cTnI was quantifiable at all time intervals tested in all animals treated with iso. The Erenna system provides sensitive measurement of cTnI in rats, dogs, and monkeys, makes it possible to determine small changes from normal concentrations, and provides cTnI values from small volumes of serum.
血清心肌肌钙蛋白I(cTnI)已在众多动物模型中被确认为心脏毒性的生物标志物;然而,由于敏感性问题,毒理学研究中使用的健康、静息动物的cTnI浓度尚未确定。使用Erenna系统对健康大鼠、狗和猴子以及用盐酸异丙肾上腺素(iso)处理的大鼠、狗和猴子的血清进行了检测。Erenna cTnI检测对人、大鼠、狗和猴子的cTnI的敏感性均<1 ng/L。所有物种均观察到线性反应(R(2)=0.99)。精密度研究得出,在1.6至5000 ng/L之间,曲线拟合定量的批间变异系数为2%至4%,在0.78 ng/L时为23%。Erenna和贝克曼Access cTnI之间具有很强的相关性(R(2)=0.99)。健康动物的cTnI浓度范围为1至9 ng/L。在对用iso处理的动物进行的纵向研究中,对照赋形剂处理组大鼠的cTnI浓度为10 - 20 ng/L(N = 10),狗的给药前值为2 - 3 ng/L(N = 3)。用Erenna检测系统测量,在用iso处理的所有动物的所有测试时间间隔内,cTnI均可定量。Erenna系统可对大鼠、狗和猴子的cTnI进行灵敏测量,能够确定与正常浓度的微小变化,并可从小体积血清中获得cTnI值。