The treatment with all-trans retinoic acid causes apoptosis without chromosomal instability in adipose-derived stem cells and might act starting the browning process

Authors

DOI:

https://doi.org/10.33448/rsd-v11i3.26787

Keywords:

Mesotherapy; Cytotoxicity; Adipose-derived stem cells; ATRA; Browning.

Abstract

Introduction: The knowledge about the biology of obesity and apoptosis induction of adipose-derived stem cells (ADSCs) may support in the development of new therapies. Objective: The present research aimed to investigate the toxicogenic effect of all-trans retinoic acid (ATRA) as well as its influence in the adipogenic differentiation and expression of genes related to DNA damage, cell cycle and thermogenesis. Methodology: Cell cultures of human adipose-derived stem cells were treated for 12 hours with ATRA (20.75 μM) and were performed the adipogenic differentiation, comet assay, micronucleous, cell death, cell cycle and qPCR. Results: The ATRA treatment decreased the capacity of adipogenic differentiation of ADSCs. The comet assay demonstrated increase in nucleoid frequency with genomic damage and scoring. However, these damages were not fixed at the chromosome level, since the tail moment was not significant. The treatment with ATRA increased cytotoxicity and increased cell death by apoptosis. The relative expression of CHEK-1, CHEK-2, CDC25A, CDC25C, ATM and ATR decreased and only UCP1 increased significantly. Conclusion: The results of the present study demonstrate that the use of ATRA induces genomic damage in ADSCs, although it was eliminated in the apoptosis process. Therefore, administration of ATRA in ADSCs did not cause chromosomal instability, which suggests toxicogenic safety. Also it was considered that ATRA might active the browning effect. Thus, this compound is considered a promising candidate for the development of novel therapies for the treatment of obesity and / or localized fat by the use of mesotherapy.

Author Biographies

Andréia Conceição Milan Brochado Antoniolli-Silva, Universidade Federal de Mato Grosso do Sul

Stem Cell, Cell Therapy and Toxicological Genetics Research Centre (CeTroGen), “Maria Aparecida Pedrossian” University Hospital, Brazilian Hospital Services Company (EBSERH), Campo Grande, Mato Grosso do Sul, Brazil

Federal University of Mato Grosso do Sul (UFMS), Graduate Program in Health and Development in the Central-West Region, Faculty of Medicine (FAMED), Campo Grande, Mato Grosso do Sul, Brazil

Rodrigo Juliano Oliveira, Universidade Federal de Mato Grosso do Sul; Universidade Estadual de Londrina

 Stem Cell, Cell Therapy and Toxicological Genetics Research Centre (CeTroGen), “Maria Aparecida Pedrossian” University Hospital, Brazilian Hospital Services Company (EBSERH), Campo Grande, Mato Grosso do Sul, Brazil

Federal University of Mato Grosso do Sul (UFMS), Graduate Program in Health and Development in the Central-West Region, Faculty of Medicine (FAMED), Campo Grande, Mato Grosso do Sul, Brazil

State University of Londrina (UEL), Graduate Programme in Genetics and Molecular Biology, Department of General Biology, Londrina, Paraná, Brazil

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Published

07/03/2022

How to Cite

SCHWEICH-ADAMI, L. de C. .; ANTONIOLLI-SILVA, A. C. M. B. .; OLIVEIRA, R. J. The treatment with all-trans retinoic acid causes apoptosis without chromosomal instability in adipose-derived stem cells and might act starting the browning process . Research, Society and Development, [S. l.], v. 11, n. 3, p. e53511326787, 2022. DOI: 10.33448/rsd-v11i3.26787. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/26787. Acesso em: 13 jun. 2024.

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Health Sciences