Exposure of mammalian cells to oxidative stress can result in DNA damage that adversely affects many cell processes. We used bulk electrolysis in an electrochemical system and capillary electrophoresis (CE) to control and measure the effect of oxidative stress on DNA. Calf thymus DNA and a fluorescently labeled DNA sizing ladder were subjected to fixed oxidizing potentials using a reticulated vitreous carbon electrode (RVC) and their fragmentation was measured with the use of CE. The resulting electropherograms showed that the oxidative treatment resulted in DNA fragmentation. Poly adenosine (Poly A) 40mer and poly guanosine (Poly G) 40-mer oligonucleotides were exposed to a controlled oxidative environment at constant potential values E = 0.5 V, 1.0 V, 1.5 V, and 2 V (vs Ag/AgCl) for 1 hour in 0.1 mol/L potassium phosphate buffer pH 7.3. The treated DNA fragments were analyzed by CE. The areas of the CE peaks were measured and the percentage of DNA fragmentation was calculated. Only minor fragmentation was observed when oligonucleotides were exposed to E = 0.5 V, with strand scission starting at electrode potentials E > 1.0 V. The E = 2.0 V treatment resulted in approximately 50% fragmentation of Poly A, compared to approximately 15% for the Poly G. These results, using DNA as a test model, demonstrate that controlled-potential electrolysis can be used to produce desired levels of oxidative damage to biomaterials without the need to use oxidative chemicals, which are difficult to control and relate to thermodynamic models.Nearly all living organisms store their genetic information in DNA. Any mutation in DNA can lead to disruption in cell processes. A common DNA damage causal factor is oxidative stress that reflects an imbalance between the systemic manifestation of reactive oxygen species (ROS) and a cell's ability to readily detoxify it. External or internal disturbances in the normal redox state of cells such as inflammation, ionizing radiation, elevated iron content, and some nanoparticles can produce potent oxidizing species that potentially damage cellular components, including proteins, lipids, and DNA. 1 For DNA, oxidative stress leads to detectable structural changes such as base lesions and strand breaks. 2,3 For experimental studies, structural changes in DNA similar to the effects observed in genomic DNA can be generated by reactive oxygen species (ROS) produced by extraneous factors either directly or through intermediates. 4 ROS are either free radicals, reactive anions containing oxygen atoms, or molecules containing oxygen atoms that can produce free radicals. The relative strength of the reactive oxidative species that are implicated in causing the damage in biomolecules can be characterized by their formal potential. 5 Therefore, establishing the relationship between the strength of the oxidative action and biomolecule fate is essential to understanding the mechanistic framework of oxidative damage. Environments that mimick oxidative stress typically are generated by chemicals, radiation, UV li...

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The underlying mechanisms of disease in sickle cell disease (SCD) contribute to a multi-faceted nephropathy, commonly manifested as albuminuria. In severe SCD genotypes (e.g., HbSS), albuminuria and chronic kidney disease (CKD) are major predictors of mortality in this population. Therefore, the monitoring and management of renal function is an intrinsic part of comprehensive care in SCD. Management of nephropathy in SCD can be accomplished with SCD-directed therapies and/or CKD-directed therapies. In the past 5 years, novel disease-modifying and palliative therapies have been approved in SCD to target aspects of the disease, such as anemia, inflammation and vasculopathy. Along with conventional hydroxyurea and chronic transfusion, L-glutamine, crizanlizumab and voxelotor have all been shown to mitigate some adverse effect of SCD, and their impact on nephropathy is being investigated. CKD-directed therapies such as renin-angiotensin aldosterone (RAAS) system blockers have long been used in SCD nephropathy; however more complete long-term studies on benefits are needed. Given the impact of renal disease on survival, further assessment of the mechanisms and efficacy of these SCD- or CKD-directed therapeutic agents is essential.