Abstract
Doxorubicin (DOX) is an anthracycline antibiotic that exhibits high heart toxicity. Human-induced pluripotent stem cell-derived ventricular cardiomyocytes (hiPSC-vCMs) are important in vitro models for testing drug cardiotoxicity. Photobiomodulation therapy (PBMT) is a non-invasive therapy that stimulates cells growth and self-repair using light irradiation. This study aimed to investigate the in vitro effects of PBMT preconditioning on cardiotoxicity induced by DOX. HiPSC-vCMs were treated with PBMT for 500 s, followed by the addition of 2 μM DOX. LED irradiation preconditioning parameters were at 660 nm with an irradiance of 10 mW/cm2, performing 5 J/cm2, followed by 24-h DOX exposure (2 μM). Human iPSC-vCMs treated with 2 μM DOX or irradiated with PBMT composed the second and third groups, respectively. The control group did neither receive PBMT preconditioning nor DOX and was irradiated with a white standard lamp. Cells from all groups were collected to perform mRNA and miRNA expressions quantification. PBMT, when applied before the DOX challenge, restored the viability of hiPSC-vCMs and reduced ROS levels. Although downregulated by DOX, myocardial UCP2 mRNA expression presented marked upregulation after PBMT preconditioning. Expression of eNOS and UCP2 mRNA and NO production were decreased after DOX exposure, and PBMT preconditioning before the DOX challenge reversed these changes. Moreover, our data indicated that PBMT preconditioning lowered the miR-24 expression. Our data suggested that PBMT preconditioning ameliorated in vitro DOX-induced cardiotoxicity on transcription level, restoring NO levels and reducing oxidative stress.
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The present work was supported by grant number 2009/54225–8 from the São Paulo Research Foundation (FAPESP) and National Council for Scientific and Technological (CNPq grant number 304607/2018–5).
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All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Allan Luís Barboza Atum, José Almir Alves da Silva, and Danila Marques. Equipment and drugs were supplied by Renato Araújo Prates, Fernanda Marciano Consolim-Colombo, and Maria Claudia Costa Irigoyen. The first draft of the manuscript was written by Maria Cristina Chavantes and José Antônio Silva Júnior. Final version of the manuscript was written and edited by José Antônio Silva Júnior, and all authors commented on the previous versions of the manuscript. All authors read and approved the final manuscript.
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Atum, A.L.B., da Silva, J.A.A., Marques, D. et al. Photobiomodulation therapy preconditioning modifies nitric oxide pathway and oxidative stress in human-induced pluripotent stem cell-derived ventricular cardiomyocytes treated with doxorubicin. Lasers Med Sci 37, 1667–1675 (2022). https://doi.org/10.1007/s10103-021-03416-9
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DOI: https://doi.org/10.1007/s10103-021-03416-9