Redox homeostasis is described as the net physiologic balance between inter-convertible oxidized and reduced equivalents within subcellular compartments that remain in a dynamic equilibrium. This equilibrium is impacted by reactive oxygen species (ROS), which are natural by-products of normal cellular activity. Studies have shown that cancer cells have high ROS levels and altered redox homeostasis due to increased basal metabolic activity, mitochondrial dysfunction, peroxisome activity, as well as the enhanced activity of NADPH oxidase, cyclooxygenases, and lipoxygenases. Glioblastoma (GBM) is the most prevalent primary brain tumor in adults with a median survival of 15 months. GBM is characterized by its extreme resistance to therapeutic interventions as well as an elevated metabolic rate that results in the exacerbated production of ROS. Therefore, many agents with either antioxidant or pro-oxidant mechanisms of action have been rigorously employed in preclinical as well as clinical settings for treating GBM by inducing oxidative stress within the tumor. Among those agents are well-known antioxidant vitamin C and small molecular weight SOD mimic BMX-001, both of which are presently in clinical trials on GBM patients. Despite the wealth of investigations, limited data is available on the response of normal brain vs glioblastoma tissue to these therapeutic interventions. Currently, a sensitive and rapid liquid chromatography tandem mass spectrometry (LC-MS/MS) method was established for the quantification of a panel of oxidative stress biomarkers: glutathione (GSH), cysteine (Cys), glutathione disulfide (GSSG), and cysteine disulfide in human-derived brain tumor and mouse brain samples; this method will be enriched with additional oxidative stress biomarkers homocysteine (Hcy), methionine (Met), and cystathionine (Cyst). Using this enriched method, we propose to evaluate the thiol homeostasis and the redox state of both normal brain and GBM in mice after exposure with redox-active therapeutics. Our results showed that, compared to normal brain (in intact mice), GBM tissue has significantly lower GSH/GSSG and Cys/CySS ratios indicating much higher oxidative stress levels. Contralateral “normal” brain tissue collected from the mice with intracranial GBM were also under significant oxidative stress compared to normal brains collected from the intact mice. Importantly, normal brain tissue in both studies retained the ability to restore redox homeostasis after treatment with a redox-active therapeutic within 24 hours while glioblastoma tissue does not. Ultimately, elucidating the differential redox response of normal vs tumor tissue will allow for the development of more redox-active agents with therapeutic benefit.

Synthetic plastics are ubiquitously used in a broad range of applications, including food and drink packaging. Plastics often contain chemical additives, including bisphenols, phthalates, and terephthalic acid, which can degrade under thermal stress. The environmental presence of these chemicals is cause for public concern, especially in consumer products that utilize plastic packaging, as many have been identified as endocrine disruptors. This study sought to determine exposure to phthalates, bisphenols, and terephthalic acid by quantifying a broad spectrum of these analytes within three bottled water brands at varying temperature exposure levels using the combination of solid phase extraction followed by isotope dilution liquid chromatography-tandem mass spectrometry. Monobenzyl phthalate was detected in two of the three brands after bottles were heated to ~100 °C, ranging from 98 – 107 ng/L, and bisphenol A was detected in one brand at ~100 °C at an average concentration of 748 ± 36 ng/L. Subsequent mass loading calculations demonstrated that bioaccumulation of BPA from Brand C after high levels of temperature exposure well exceeded the tolerable daily intake (TDI). Findings in this study indicate that consumers should not be expected to incur harmful exposures to the target compounds under normal conditions as analytes were not measured in water bottle samples at 25 °C or 60 °C. Further studies should explore a more nuisance approach to heating over long durations, including that of ultraviolet exposure.