Evaluation of doxorubicin toxicity on cardiomyocytes using a dual functional extracellular biochip.
Nowadays, cardiotoxicity induced by clinical drugs presents a high prevalence and has aroused great attention onto the effective and reliable drug evaluation before clinical treatment. Doxorubicin (Adriamycin), as a type of anthracycline chemotherapy agent for cancer treatment, was restricted in the clinical use because of its cardiotoxicity. In the present work, a dual functional biochip ExCell integrated with microelectrode arrays and interdigitated electrodes was designed to study the electrophysiological function and physical state of cardiomyocytes under the treatment of doxorubicin. Extracellular field potentials and cell-substrate impedance were measured to respectively express these two functions simultaneously in the same culture. The result detected by ExCell presented a portrait of cardiotoxicity induced by doxorubicin. The amplitude of extracellular field potentials decreased to 93%, 82% and 50% at 50 min treatment of doxorubicin with concentrations of 20 μM, 100 μM and 200 μM, respectively. Successively, beating rate decrease, beat-to-beat variation and Ca(2+) flux manifested severe abnormality. The cell-substrate impedance declined continuously in the depressing process of electrophysiological function and cell death was induced in high concentration treatment. All these result indicate that the biochip ExCell has the potential to be a fast-response and subtle tool for high-throughput drug evaluation assays.
Xiao
Lidan
L
Biosensor National Special Lab, Department of Biomedical Engineering, Zhejiang University, Hangzhou 310027, PR China.
Hu
Zhaoyin
Z
Zhang
Wei
W
Wu
Chengxiong
C
Yu
Hui
H
Wang
Ping
P
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D015374:Biosensing Techniques / Q000295:instrumentation* / Q000379:methods; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D004317:Doxorubicin / Q000633:toxicity*; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation* / Q000379:methods; D017097:Electric Impedance; D055724:Electrophysiological Phenomena; D004867:Equipment Design; D005110:Extracellular Space / Q000187:drug effects / Q000502:physiology; D006801:Humans; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D051381:Rats
D000970:Antineoplastic Agents; D004317:Doxorubicin