Cardiac toxicity of phenanthrene depends on developmental stage in Atlantic cod (Gadus morhua)

Complex mixtures like crude oil, and single components such as Phenanthrene (Phe), induce cardiotoxicity by interfer- ing with excitation-contraction coupling. However, recent work has demonstrated that the timing of pollutant expo- sure during embryogenesis greatly impacts the degree of cardiac dysfunction caused. Here, we aimed to clarify the temporal dependence of Phe toxicity and the downstream effects of cardiac dysfunction using Atlantic cod (Gadus morhua). Phe (nominal concentration, 1.12 mu mol/L), or the L-type-calcium channel blocker Nicardipine (Nic) (nominal concentration, 2 and 4 mu mol/L), were individually applied to cod embryos either during cardiogenesis (early) or after the onset of cardiac function (late). Phe toxicity was highly dependent on the timing of exposure. Exposure after the onset of cardiac function (i.e. late) caused more severe cardiac and extracardiac abnormalities at 3 days post hatching (dph) than early exposure. Late Phe exposure resulted in a smaller ventricle, eliminated ventricular contraction, and reduced atrial contraction. In contrast, early Phe exposure did not have an effect on cardiac development and function. This temporal difference was not as evident in the Nic treatment. Early Nic exposure created similar morphological phenotypes to the late Phe exposure. The two treatments (early Nic and late Phe) also shared a cardiofunctional phe- notype, comprised of eliminated ventricular, and reduced atrial, contraction. These data suggest that extracardiac ab- normalities, such as the craniofacial deformities seen after late embryonic exposure to cardiotoxic oil components and mixtures, are mostly downstream effects of cardiac dysfunction.

Automated summary

Crude oil and single components like Phenanthrene can cause cardiotoxicity by interfering with excitation-contraction coupling. This study shows that the timing of exposure greatly affects the severity of cardiac dysfunction, with late exposure causing more severe abnormalities than early exposure. Early exposure to Phenanthrene had no effect on cardiac development and function.