Tamoxifen induces eryptosis through calcium accumulation and oxidative stress.

Chemotherapy-related anemia is a major obstacle in anticancer therapy. Tamoxifen (TAM) is an antiestrogen prescribed for breast cancer patients with hemolytic potential and apoptotic properties in nucleated cells. However, the eryptotic activity of TAM has hitherto escaped the efforts of investigators. RBCs from apparently healthy volunteers were treated with 1-50 µM of TAM for 24 h at 37 °C. Hemoglobin leakage and LDH, AST, and AChE activities were photometrically determined while K+, Na+, and Mg2+ were detected by ion-selective electrode. Flow cytometry was used to identify eryptotic cells by annexin-V-FITC, intracellular Ca2+ by Fluo4/AM, sell size and morphology by FSC and SSC signals, respectively, and oxidative stress by H2DCFDA. Whole blood was also exposed to 30 µM of TAM for 24 h at 37 °C to examine the toxicity of TAM to WBCs and platelets. TAM caused Ca2+-independent, dose-responsive hemolysis accompanied by K+, LDH, and AST leakage without improving the mechanical stability of RBCs in hypotonic environments. TAM treatment also increased the proportion of cells positive for annexin-V-FITC, Fluo4, and DCF, along with diminished FSC and SSC signals and AChE activity. Notably, TAM toxicity was aggravated by sucrose but abrogated by vitamin C, PEG 8000, and urea. Moreover, TAM exhibited distinct cytotoxic profiles against leukocytes and platelets. TAM-induced eryptosis is characterized by breakdown of membrane asymmetry, inhibition of AChE activity, Ca2+ accumulation, cell shrinkage, and oxidative stress. Vitamin C, PEG 8000, and urea may hold promise to subvert the undesirable toxic effects of TAM on RBCs.

Comparative Metabolic Characterization of Extraintestinal Pathogenic Escherichia coli Blood Isolates from Saudi Arabia.

Background: The prevalence of bloodstream infections caused by extraintestinal pathogenic Escherichia coli (ExPEC) has increased substantially. E. coli ST131 is one of the dominant ExPEC clones among E. coli bacteremia population. Metabolism can trigger the pathogenesis of some bacterial isolates, and here we evaluated and compared the metabolic traits of E. coli bacteremia isolates including ß-lactamase (BL)/extended-spectrum ß-lactamase (ESBL)-positive and ESBL-negative isolates and ST131 and non-ST131 isolates. Methods: The metabolic profiles of thirty E. coli isolates, obtained from blood samples for hospitalized individuals at a tertiary healthcare facility in Riyadh, were determined using HiMedia carbohydrate test strips. The difference in the utilization ability between isolate groups was then statistically assessed. Results: Our data found that non-BL/ESBL producers were of low metabolic capacity compared with ESBL-positive isolates although the difference remained insignificant. Higher levels of utilization for some carbohydrates, such as fructose and trehalose, were detected among ST131 isolates when compared with non-ST131, and ST131 was also significantly associated with metabolizing rhamnose. The mean bio-score of both isolate groups was insignificant. We showed no link between metabolism and antimicrobial susceptibility profiles among tested blood isolates. Conclusion: ST131 blood isolates were slightly higher in their carbohydrate utilization activity than non-ST131. More importantly, ST131 isolates were significantly capable of metabolizing rhamnose. Future research should focus on the factors that might drive the success of major ExPEC clones such as ST131.