Wu Huifeng, Zhang Xiaoyu, Li Xiaojing, Li Zhongfeng, Wu Yijie, Pei Fengkui
Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, People's Republic of China.
Anal Biochem. 2005 May 1;340(1):99-105. doi: 10.1016/j.ab.2005.01.057.
Hepatotoxicities were induced in rats using alpha-naphthylisothiocyanate (ANIT), carbon tetrachloride (CCl(4)), and hydrazine (HYD). Male Wistar rats were treated with three typical hepatotoxins, and serum samples were collected after 48 h. Biochemical effects of these toxins on plasma composition were evaluated by high-resolution (1)H nuclear magnetic resonance (NMR) spectroscopy of serum. The biochemical effects of CCl(4) were characterized by an elevated level of 3-d-hydroxybutyrate (HB), acetoacetate (Aca), and creatinine (Cn) in serum, and ANIT led to increases in the amounts of low-density lipoprotein (LDL), alanine, acetate, glycoprotein, succinate, Cn, acetone, 3-d-hydroxybutyrate, and Aca. For the HYD-treated group, LDL, HB, acetate, and Cn were obviously increased in serum. The region delta 0.0-10.0 of each spectrum was segmented into 0.04 ppm. The area under the spectrum was calculated for each segmented region and expressed as an integral value. After removal of the water signal (delta 4.6-5.0) the remaining 235 intensity-related descriptors were used for the pattern recognition analysis. Principal component analysis was used to visualize the similarities and differentiations in biochemical profiles of serum from the rats treated with various hepatotoxins. This work showed the power of the combination of NMR and pattern recognition for the study of biochemical effects of xenobiotics.
使用α-萘基异硫氰酸酯(ANIT)、四氯化碳(CCl₄)和肼(HYD)在大鼠中诱导肝毒性。将雄性Wistar大鼠用三种典型的肝毒素进行处理,并在48小时后收集血清样本。通过血清的高分辨率¹H核磁共振(NMR)光谱评估这些毒素对血浆成分的生化作用。CCl₄的生化作用表现为血清中3-羟基丁酸(HB)、乙酰乙酸(Aca)和肌酐(Cn)水平升高,而ANIT导致低密度脂蛋白(LDL)、丙氨酸、乙酸盐、糖蛋白、琥珀酸盐、Cn、丙酮、3-羟基丁酸和Aca的量增加。对于HYD处理组,血清中的LDL、HB、乙酸盐和Cn明显增加。每个光谱的δ 0.0 - 10.0区域被分割为0.04 ppm。计算每个分割区域下的光谱面积并表示为积分值。去除水信号(δ 4.6 - 5.0)后,将其余235个与强度相关的描述符用于模式识别分析。主成分分析用于可视化来自用各种肝毒素处理的大鼠血清生化谱中的相似性和差异。这项工作展示了NMR和模式识别相结合在研究异生物素生化作用方面的能力。