Efeito do pré-condicionamento com fotobiomodulação na expressão de microRNAs relacionados à disfunção cardíaca em cardiomiócitos ventriculares humanos derivados de células-tronco pluripotentes submetidos à doxorrubicina

Abstract

INTRODUCTION: Cardiotoxicity is a widely recognized adverse effect associated with cancer therapy, with potential serious repercussions in the short and long term. Doxorubicin (DOX), is a chemotherapy drug frequently used in the treatment of malignant neoplasms due to its proven effectiveness, however, it also presents, among its main side effects, cardiac toxicity, which raises great concern regarding its use. Photobiomodulation (FBM) triggers a cascade of molecular events with therapeutic potential in cardiovascular diseases. The use of light emitting diode (LED) has been explored as a source of treatment to promote beneficial effects in biological tissues. OBJECTIVE: To analyze the expression profile of miRNAs in ventricular cardiomyocytes, derived from pluripotent stem cells (HiPSC-vCMs), subjected to Photobiomodulation preconditioning, exposed to doxorubicin. METHODS: In vitro experimental study, conducted with HiPSC-vCMs, subjected to preconditioning with photobiomodulation and exposed to doxorubicin. The HiPSC-vCMs were allocated into 3 groups: 1- Control (not exposed to DOX and FBM; irradiated with a standard light lamp; addition of sterile saline solution); 2- DOX group (addition of 2μM DOX for 24h) and 3- DOX+ FBM group (FBM preconditioning; addition of 2μM DOX). Preconditioning with FBM was performed with an LED device, emitting light with length wave of 660nm ± 10nm, irradiance of 10 mW/cm2, for 500 seconds, resulting in a dose of 5 J/cm2. For the cellular cytotoxicity assay, we used real-time PCR to quantify microRNA expression. RESULTS: After 24h of doxorubicin administration in HiPSC-vCMs, we verified the modulation of the expression of 12 miRNAs (92%), related to cellular dysfunction in vitro. FBM was performed before DOX administration, the expression of 9 miRNAs (69%) was modulated by irradiation. CONCLUSION: The results indicated that doxorubicin was capable of altering the expression of microRNAs, related to cellular dysfunction, in cardiomyocytes derived from stem cells. However, when these cells were subjected to photobiomodulation, a significant reduction in the deleterious effect of doxorubicin was observed in most experimental assays.