Author/Authors :
Bashiri Dezfouli, Ali Department of Basic Sciences - Faculty of Veterinary Medicine - University of Tehran, Tehran, Iran , Pourfathollah, Ali Akbar Department of Immunology - Faculty of Medical Science - Tarbiat Modares University, Tehran, Iran , Salar-Amoli, Jamileh Department of Basic Sciences - Toxicology and Animal Poisoning Research Center - Faculty of Veterinary Medicine - University of Tehran, Tehran, Iran , Khosravi, Mohammad Department of Pathobiology - Faculty of Veterinary Medicine - Shahid Chamran University of Ahvaz, Ahvaz, Iran , Nikogoftar-Zarif, Mahin Blood Transfusion Research Center - High Institute for Research and Education in Transfusion Medicine, Tehran, Iran , Yazdi, Mina Faculty of Veterinary Medicine - University of Tehran, Tehran, Iran , Ali-Esfahani, Tahereh Toxicology and Animal Poisoning Research Center - Faculty of Veterinary Medicine - University of Tehran, Tehran, Iran
Abstract :
Background: Doxorubicin, by aggregating in bone marrow, causes genotoxic effects, and thus reduces the repair ability of cells.
The present study was conducted as an in vitro evaluation of age effects on the cytotoxicity induced by doxorubicin in mesenchymal
stem cells (MSCs).
Methods: The MSCs of female BALB/c mice aged 1, 8, and 16 months were separated, characterized, and subsequently evaluated in
cellular growth media. After 24 hours, exposure of the MSCs of the 3 groups of mice to doxorubicin (25, 50, 100, 200, 400, 800, 1200
nM) and cytotoxicity were assessed, and the sublethal dose was determined using flow cytometry technique and lactate dehydrogenase
(LDH) release assay.
Results: The IC50 values determined by flow cytometry for the separated MSCs of 1 young, 8 middle- aged, and 16 old mice were
and respectively. Interestingly, the results of these 2 methods in determining cytotoxicity were in agreement, and a concentration of
approximately 25 nM was considered to be the shared sublethal dose for different ages.
Conclusion: The results indicated that MSCs of middle-aged mice were more resistant to the toxic effects of the drug. Besides,
MSCs separated from the old mice were the most sensitive to chemotherapy and its side effects such as disruptions of cell proliferation
and viability. These disruptions can be ascribed to the alteration of function and physiological processes with age. Determining proper
concentration of doxorubicin drug to destruct cancerous cells based on age and individual sensitivity can minimize the amount of toxicity.
Keywords :
Age , Cytotoxicity , Mesenchymal Stem Cells , Doxorubicin