Photobiomodulation therapy preconditioning modifies nitric oxide pathway and oxidative stress in human-induced pluripotent stem cell-derived ventricular cardiomyocytes treated with doxorubicin

Autor(es)

Barboza Atum, Allan Luis ; Alves da Silva, Jose Almir ; Marques, Danila ; Prates, Renato Araujo ; Consolim-Colombo, Fernanda Marciano ; Costa Irigoyen, Maria Claudia ; Dalboni, Maria Aparecida ; Chavantes, Maria Cristina ; Silva Jr, Jose Antonio

• Tipo de documento: Artigo Científico
• Fonte: Lasers in Medical Science; v. N/A, p. 9-pg., 2021-09-18.

Resumo

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 mu M DOX. LED irradiation preconditioning parameters were at 660 nm with an irradiance of 10 mW/cm(2), performing 5 J/cm(2), followed by 24-h DOX exposure (2 mu M). Human iPSC-vCMs treated with 2 mu M 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. (AU)

• Processo FAPESP: 09/54225-8 - Fisiopatologia da insuficiência cardíaca congestiva
• Beneficiário: Paulo Jose Ferreira Tucci
• Modalidade de apoio: Auxílio à Pesquisa - Temático