Zhao Jie, Ma Long, Xiang Xun, Guo Qing-Lian, Jiang Feng-Lei, Liu Yi
State Key Laboratory of Virology & Key Laboratory of Analytical Chemistry for Biology and Medicine (MOE), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072, PR China.
Department of Clinical Laboratory, Zhongnan Hospital, Wuhan University, Wuhan, 430071, PR China.
Chemosphere. 2016 Jun;153:414-8. doi: 10.1016/j.chemosphere.2016.03.082. Epub 2016 Mar 28.
Gadolinium-based compounds are most widely utilized for paramagnetic contrast agents, but, the toxicological mechanism of gadolinium (Gd) had not been fully elucidated since the first report about Gd anomaly. In this work, we analyzed the effect of Gd(3+) on mitochondria in vitro by microcalorimetry. Microcalorimetry can provide detailed kinetic and thermodynamic information from thermogenic curve. At the tested concentration, Gd(3+) induced the increase of growth rate constant (k1). At high concentration (100-500 μM), the maximum power output time (tm), the decline rate constant (-k2) and the time of activity recovery phase (tR) decreased with the addition of Gd(3+) and the maximum power output (Pm) increased. At low concentration (0-100 μM), the changes were different from high concentration. From the results we concluded that the effect of different concentrations of Gd(3+) had a relationship with time, high concentration of Gd(3+) induced mitochondrial energy metabolism disturb however low concentration may promote mitochondrial adaption to physiological stresses. The effect of low concentration of Gd(3+) need more work to elucidate the mechanism. The results of total heat output (Q) and mitochondrial respiratory activities suggested high concentrations of Gd(3+) could accelerate adenosine triphosphate (ATP) consumption under respiratory system damaged.
基于钆的化合物作为顺磁性造影剂应用最为广泛，然而，自首次报道钆（Gd）异常以来，其毒理学机制尚未完全阐明。在本研究中，我们通过微量量热法分析了Gd(3+)在体外对线粒体的影响。微量量热法能够从产热曲线中提供详细的动力学和热力学信息。在测试浓度下，Gd(3+)诱导生长速率常数（k1）增加。在高浓度（100 - 500 μM）时，随着Gd(3+)的添加，最大功率输出时间（tm）、下降速率常数（-k2）和活性恢复阶段时间（tR）降低，最大功率输出（Pm）增加。在低浓度（0 - 100 μM）时，变化与高浓度不同。从结果中我们得出结论，不同浓度的Gd(3+)的作用与时间有关，高浓度的Gd(3+)诱导线粒体能量代谢紊乱，而低浓度可能促进线粒体对生理应激的适应。低浓度Gd(3+)的作用机制需要更多研究来阐明。总热输出（Q）和线粒体呼吸活性结果表明，高浓度的Gd(3+)在呼吸系统受损时可加速三磷酸腺苷（ATP）的消耗。
