In vitro study of the protective effect of manganese against vanadium-mediated nuclear and mitochondrial DNA damage. (January 2020)

• Record Type: Journal Article
• Authors: Rivas-García, Lorenzo; Quiles, José L.; Varela-López, Alfonso; Arredondo, Miguel; Lopez, Paulina; Diéguez, Antonio Rodríguez; Montes-Bayon, María; Aranda, Pilar; Llopis, Juan; Sánchez-González, Cristina
• Is Part Of: Food and chemical toxicology. Volume 135(2020)
• Publication Date: 2020-01
• Subjects: Vanadium -- Manganese -- DNA -- Nucleus -- Mitochondria -- HepG2 cells; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2019.110900
• Languages: English
• ISSNs: 0278-6915

Abstract

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. Graphical abstract: Image 1 Highlights: Exposure to vanadium (as BMOV) of HepG2 cells increases the cellular content of V and Mn. Exposure to vanadium (as BMOV) of HepG2 cells damages nuclear and mitochondrial DNA and decreases cell viability. Exposure to manganese (as MnCl2 ) of HepG2 cells decreases the cellular content of V and Mn. Exposure to a combination of V and Mn of cells minimizes the deleterious action of V on DNA, restoring cell viability. V and Mn combined therapy reduces vanadium toxicity possibly due to the inhibition of V cellular content caused by Mn.