Cardiotoxic effects of methamphetamine associated with electrophysiological and epigenetic aberrations in zebrafish

Abstract

AbstractLong-term methamphetamine (Meth) abuse damages functional and molecular changes in the brain that causes chronic and relapsing disease. In this study, we sought to investigate a relationship between cardiotoxicity and arrhythmia with associated Meth abuse in zebrafish to identify and to understand the adverse cardiac symptoms associated with Meth as well as to assess the applicability of zebrafish as an appropriate model for cardiac-related drug screening studies. Over a two-week duration, zebrafish were first treated with various concentrations of Meth, ranging from 0 to 50 μM. Immediately after treatment, zebrafish underwent electrocardiogram (ECG) measurement for electrophysiological analysis. Results show that a higher incidence of increased heart rate over the duration of the experiment, corroborating with results from previous human case studies involving Meth users. However, abnormalities commonly cited in those same case studies, such as prolongation of QTc, were not significantly presented in obtained ECG recordings. We have also conducted genetic, epigenetic, and histochemical analysis in an attempt to understand the cardiotoxic effects of Meth on zebrafish cardiac function. These results suggested myocardial damage and decrease in gene expression associated with normal physiological function. Finally, this paper provides insights into potential reasons for the apparent discrepancies in our data with prior research as well as an outlook of zebrafish cardiotoxic drug screening studies.