From Oil Spills to Air Pollution: The Emergence of Phenanthrene as a Ubiquitous Cardiac Toxicant

Polycyclic aromatic hydrocarbons (PAHs) are released into the environment primarily through industrial processes and the incomplete combustion of organic matter. Their persistence in air, water, and soil facilitates widespread environmental distribution and exposure that directly impact the health of humans, other animals, and ecosystems. In recent years, the 3-ringed PAH phenanthrene has drawn particular interest for its specific cardiotoxicity. Phenanthrene can be transformed in the environment and within the body, leading to metabolites that can also influence heart function. Phenanthrene and its derivatives alter the electrical activity of the heart by inhibiting repolarizing (e.g., <i>I</i> _K) currents and inhibiting depolarizing (e.g., <i>I</i> _Na and <i>I</i> _Ca) currents, which increase the probability of arrhythmias. Phenanthrene and its derivatives also impact cardiac contractility by reducing the amplitude of the intracellular Ca2+ transient in all species examined to date. This review begins by describing the sources and sinks of environmental phenanthrene and how it enters and accumulates within organisms. It then focuses on the potential for, and mechanisms of, modulation of cardiac activity by phenanthrene and its derivatives at the molecular, cellular, intact heart, and whole organism levels. The results provide a comprehensive summary of the propensity of phenanthrene to modulate vertebrate cardiac function, from fish exposed via crude oil to humans breathing polluted air.