Polyphenol effects on CuO-nanoparticle-mediated DNA damage, reactive oxygen species generation, and fibroblast cell death

Carlos Angelé-Martínez; Fathima S Ameer; Yash S Raval; Guohui Huang; Tzuen-Rong J Tzeng; Jeffrey N Anker; Julia L Brumaghim

doi:10.1016/j.tiv.2021.105252

Polyphenol effects on CuO-nanoparticle-mediated DNA damage, reactive oxygen species generation, and fibroblast cell death

Toxicol In Vitro. 2022 Feb:78:105252. doi: 10.1016/j.tiv.2021.105252. Epub 2021 Oct 5.

Authors

Carlos Angelé-Martínez¹, Fathima S Ameer², Yash S Raval³, Guohui Huang⁴, Tzuen-Rong J Tzeng⁵, Jeffrey N Anker⁶, Julia L Brumaghim⁷

Affiliations

¹ Department of Chemistry, Clemson University, Clemson, SC 29634-0973, USA. Electronic address: cangele@g.clemson.edu.
² Department of Chemistry, Clemson University, Clemson, SC 29634-0973, USA. Electronic address: fathima@g.clemson.edu.
³ Department of Biological Sciences, Clemson University, Clemson, SC 29634, USA. Electronic address: yraval@g.clemson.edu.
⁴ Department of Biological Sciences, Clemson University, Clemson, SC 29634, USA. Electronic address: ghuang@clemson.edu.
⁵ Department of Biological Sciences, Clemson University, Clemson, SC 29634, USA. Electronic address: tzuenrt@clemson.edu.
⁶ Department of Chemistry, Clemson University, Clemson, SC 29634-0973, USA. Electronic address: janker@clemson.edu.
⁷ Department of Chemistry, Clemson University, Clemson, SC 29634-0973, USA. Electronic address: brumagh@clemson.edu.

Abstract

The ability of ten polyphenolic antioxidants to prevent CuO nanoparticle (^NPCuO) and H₂O₂-mediated DNA damage and cytotoxicity was investigated. Five of the polyphenols (MEPCA, PREGA, MEGA, ECG, and EGCG) prevent ^NPCuO/H₂O₂-mediated DNA damage (IC₅₀ values of 7.5-800 μM), three have no effect (PCA, VA, and EC), and two (GA and EGC) result in increased DNA damage. Most polyphenols had similar antioxidant/prooxidant activity in the presence of ^NPCuO or free copper ions. Electron paramagnetic resonance (EPR) spectroscopy of reactive oxygen species (ROS) generated by ^NPCuO/H₂O₂ in the presence of representative polyphenols correlate with results of DNA damage studies: in the presence of ^NPCuO/H₂O₂, MEPCA prevents ROS formation, VA has no effect on ROS levels, and EGC increases ROS levels. EPR results with CuO nanoparticles washed to remove dissolved copper in solution (^wCuO) in the presence of H₂O₂/ascorbate suggest that MEPCA prevents ROS formation on the nanoparticle surface in addition to preventing ROS formation from dissolved copper. In mouse fibroblast (L929) cells, combining ^NPCuO with H₂O₂ results in significantly greater cytotoxicity than observed for either component alone. After 3 h incubation with MEPCA or MEGA, the viability loss in L929 cells induced by ^NPCuO/H₂O₂ challenge was significantly rescued at physiologically relevant polyphenol levels (1 μM). These studies show that polyphenols can protect DNA and inhibit cytotoxicity generated by ^NPCuO under oxidative stress conditions.

Keywords: Cell death prevention; CuO nanoparticles; DNA damage; Polyphenol; Prooxidant; Reactive oxygen species.

MeSH terms

Animals
Cell Death / drug effects
Cell Line
Copper / toxicity*
DNA Damage / drug effects
Fibroblasts / drug effects
Hydrogen Peroxide / toxicity
Metal Nanoparticles / toxicity*
Mice
Polyphenols / pharmacology*
Reactive Oxygen Species / metabolism

Substances

Polyphenols
Reactive Oxygen Species
Copper
Hydrogen Peroxide
cupric oxide

Abstract

MeSH terms

Substances

Grants and funding