Induction of oxidative stress by drugs and other xenobiotics is an important mechanism of cytotoxicity. However, in vitro studies on the relationship between oxidative stress and cytotoxicity in cultured cells is frequently complicated by the fact that cell culture medium components affect reactive oxygen species (ROS) exposures in ways that vary with the mode of ROS production. The objectives of this study were to first determine the mode of ROS induction by certain model compounds when they are applied to cultured cells, and then to determine how ROS induction and cytotoxicity were affected by the ROS-quenching medium component pyruvate. Three compounds, eseroline, benserazide, and pyrogallol induced H2O2 in cell culture media independent of cells. However, another compound, menadione, induced H2O2 in a manner largely dependent on the MDA-MB-231 breast cancer cells used in this study, which is consistent with its known mechanism of inducing ROS through intracellular redox cycling. 1 mM pyruvate, as well as catalase, reduced the H2O2 in culture wells with each ROS inducer tested but it only reduced the cytotoxicity of cell-independent inducers. It reduced the cytotoxicity of benserazide and pyrogallol >10-fold and of eseroline about 2.5-fold, but had no effect on menadione cytotoxicity. From this data, it was concluded that depending on the mechanism of ROS induction, whether intra- or extracellular, a ROS-quenching medium component such as pyruvate will differentially affect the net ROS-induction and cytotoxicity of a test compound.

The uridine 5'-diphospho-glucuronosyltransferase (UGT) family of enzymes is involved in the metabolism of various compounds. These enzymes transfer a hydrophilic glucuronic acid moiety to their substrates, rendering them more water soluble and amenable to excretion. The UGTs act on various endogenous substrates, such as bilirubin, 17β-estradiol, and testosterone, and drugs and other xenobiotics. The function of these enzymes is essential for the clearance of drugs and toxicants, and alteration of UGT activity is a potential cause of adverse drug—drug interactions in vivo. This has stimulated an increased interest in the study of UGT function and inhibition, and the desire to profile new drug entities against UGT enzymes, similar to CYP450 profiling. However, certain factors have hindered the development of a robust method for UGT profiling. Current methods for assessing UGT enzyme activity are laborious and involve protein precipitation and/or chromatographic separation steps, which are not amenable to rapid screening applications for UGT inhibitors or substrates. The approach presented here is a bioluminescent assay for measuring UGT enzyme activity and inhibition in vitro. Using flexible, robust instrumentation in a 384-well microplate format, this study highlights the quick and easy assay implementation for estimation of inhibition kinetics with a variety of known and suspected UGT substrates and inhibitors.

Objectives: The emergence of coronavirus disease 2019 (COVID-19), caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a global health calamity unprecedented in the modern world. The disease spread worldwide, and to date, there have been over 230 million confirmed cases of COVID-19, including approximately 4.7 million deaths. Mutant variants of the virus have raised concerns about additional pandemic waves and threaten to reverse our progress thus far to limit the spread of the virus. These variants include Alpha, Beta, and Delta (first reported in December 2020 in the United Kingdom, South Africa, and India, respectively) and Gamma (reported in January 2021 in Brazil). In some cases, countries have even reported a rise in daily cases higher than the first wave in March 2020. Given the rapidly evolving nature of COVID-19 and subsequent new findings and updates each day, this review article aims to comprehensively summarize the etiology, pathophysiology, and clinical features of SARS-CoV-2 infection. Methods: A systematic review of the literature was performed in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to gain insight into the transmissibility, pathogenesis, entry factors, and immune response of COVID-19. Specifically, Pubmed and Google Scholar databases were searched to identify any relevant articles. References within the included articles were reviewed. Published articles related to search criteria from the onset of the COVID-19 pandemic to March 2022 were included. Results: Viral transmissibility is predominantly affected by the modes of transmission, various mutations on the nucleocapsid protein and endoRNAse, gender, age, and other factors. The pathophysiological mechanism is generally unknown, although the clinical manifestations such as headache, loss of smell and taste, vomiting, diarrhea, multiorgan failure, and dermatological and cardiovascular complications are well documented. The progression of infection depends on the immunopathological response and the innate/adaptive immunity. Conclusion: Our review has summarized the latest knowledge about SARS-CoV2. However, as the pandemic continues to spread across the continents, there is an urgent need for more research on potentially emerging coronaviruses and the development of a universal coronaviruses vaccine to put the pandemic behind us.

The effect of vitamin D on DU4475 cell viability was different than in other TNBC cells. The effect of PTX on DU4475 cells was enhanced with vitamin D. MDA-MB-231 cells were relatively resistant to the effects of PTX.

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