Anticancer agent doxorubicin toxicity to <i>in vitro X. laevis</i> tadpole organ heart and mature frog heart and liver mitochondria

One of the cancer drugs discharged into hospital wastewater, doxorubicin (DOX), is suspected of toxic effects on aquatic organisms. Cardiac and mitochondrial toxicity of DOX was investigated using cultured Xenopus (X.) laevis tadpole heart and mature frog liver mitochondria as materials. While 10^-9 DOX was not found to suppress heart rate, 10^-7 M DOX caused short-term heartbeat suppression in a preliminary experiment. Compared to the heart rate of untreated organ hearts kept in heart-organ medium without hydrogen-peroxide oxidoreductase enzyme catalase (CAT) for 9 days, that of 10^-8 M DOX-treated hearts decreased over time. The heartbeat suppression was improved by adding CAT to the heart culture medium, suggesting that DOX induces reactive oxygen species (ROS) in cultured tadpole hearts. Mitochondrial swelling assay was conducted. DOX was found to suppress slight swelling of heart and liver mitochondria with adenosine triphosphate (ATP) treatment. DOX also suppressed Ca⁺⁺-induced swelling of heart and liver mitochondria with ATP treatment. These findings suggest that the side effects of DOX on X. laevis heart and liver mitochondria are likely similar to those of cyclosporin A (CsA), an inhibitor of mitochondrial permeability transition pore (MPT) and also a ROS generator, leading to cardiac and mitochondrial dysfunction.