RT info:eu-repo/semantics/article T1 Arrhythmic Effects Evaluated on Caenorhabditis elegans: The Case of Polypyrrole Nanoparticles A1 Srinivasan, Sumithra Yasaswini A1 Álvarez Illera, María Pilar A1 Kukhtar, Dmytro A1 Benseny-Cases, Núria A1 Cerón, Julián A1 Álvarez Martín, Javier A1 Fonteriz García, Rosalba Inés A1 Montero Zoccola, María Teresa A1 Laromaine, Anna K1 Polypyrrole nanoparticles, C. elegans, small animal models, arrhythmia models, cardiotoxicity AB Experimental studies and clinical trials of nanoparticles for treating diseases are increasing continuously.However, the reach to the market does not correlate with these efforts due to the enormous cost, several years of development, and off-target effects like cardiotoxicity. Multicellular organisms such as the Caenorhabditis elegans (C. elegans) can bridge the gap between in vitro and vertebrate testing as they can provide extensive information on systemic toxicity and specific harmful effects through facile experimentation following 3R EU directives on animal use. Since the nematodes’ pharynx shares similarities with the human heart, we assessed the general and pharyngeal effects of drugs andpolypyrrole nanoparticles (Ppy NPs) using C. elegans. The evaluation of FDA-approved drugs, such as Propranolol and Racepinephrine reproduced the arrhythmic behavior reported in humans and supported the use of this small animal model. Consequently, Ppy NPs were evaluated due to their research interest in cardiac arrhythmia treatments. The NPs’ biocompatibility was confirmed by assessing survival, growth and development, reproduction, and transgenerational toxicity in C. elegans. Interestingly, the NPs increased the pharyngeal pumping rate of C. elegans in two slow-pumping mutant strains, JD21 and DA464. Moreover, the NPs increased the pumping rate over time, which sustained up to a day post-excretion. By measuring pharyngeal calcium levels, we found that the impact of Ppy NPs on the pumping rate could be mediated through calcium signaling. Thus, evaluating arrhythmic effects in C. elegans offers a simple system to test drugs and nanoparticles, as elucidated through Ppy NPs. PB ACS Publications SN 1936-0851 YR 2023 FD 2023 LK https://uvadoc.uva.es/handle/10324/66236 UL https://uvadoc.uva.es/handle/10324/66236 LA eng NO ACS Nano, Agosto 2023, 17, 17273−17284 NO Producción Científica DS UVaDOC RD 27-nov-2024