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In vitro study of the protective effect of manganese against vanadium-mediated nuclear and mitochondrial DNA damage
Lorenzo Rivas-García1, José L Quiles2, Alfonso Varela-López2
1Biomedical Research Centre, Institute of Nutrition and Food Technology, Department of Physiology, Faculty of Pharmacy, University of Granada, Avda. del Conocimiento s/n. 18071 Armilla, Granada, Spain; Sport and Health Research Centre. University of Granada, C/. Menéndez Pelayo 32. 18016 Armilla, Granada, Spain.
Abstract:
We aimed to study the effect of vanadium(V) exposure on cell viability, nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) and to elucidate if these effects can be reverted by co-exposure to V and manganese (Mn). HepG2 cells were incubated with various concentrations of bis(maltolato)oxovanadium(IV) or MnCl2 for 32 h for viability study. The higher concentrations (59 μM V, 54 nM Mn and 59 μM V+54 nM Mn) were used to study DNA damage and uptake of V and Mn. Comet assay was used for the study of nDNA damage; mtDNA damage was studied by determining deletions and number of copies of the ND1/ND4 mtDNA region. Cellular content of V and Mn was determined using ICPMS. Cellular exposure to 59 μM V decreased viability (14%) and damaged nDNA and mtDNA. This effect was partially prevented by the co-exposure to V + Mn. Exposure to V increased the cellular content of V and Mn (812.3% and 153.5%, respectively). Exposure to Mn decreased the content of V and Mn (62% and 56%, respectively). Exposure to V + Mn increased V (261%) and decreased Mn (56%) content. The positive effects on cell viability and DNA damage when incubated with V + Mn could be due to the Mn-mediated inhibition of V uptake.
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