Involvement of Calcium, Reactive Oxygen Species, and ATP in Hexavalent Chromium-Induced Damage in Red Blood Cells

Abstract

Aim: The aim of this study was to investigate the mechanisms of Cr⁶⁺-induced red blood cells (RBCs) damage. Methods: The effect of Cr⁶⁺ exposure on RBCs was evaluated by hemolytic rate and blood gas assays. After exposure to 20 μM Cr⁶⁺, the percentage of phosphatidylserine (PS)-exposing cells, intracellular Ca²⁺, reactive oxygen species (ROS), and ATP levels were evaluated, and cell morphology was observed. RBCs were exposed to Cr⁶⁺ in different Ringer solutions to investigate the role of changes of Ca²⁺, ROS, and ATP levels in eryptosis and morphology. Results: The Cr⁶⁺-induced damage of RBCs was dose-dependent. After a 6 h incubation with Cr⁶⁺, RBCs exhibited significant Ca²⁺ influx, ROS increase, ATP depletion, and PS exposure, but displayed no obvious change in morphology at this time point. After 24 h Cr⁶⁺ exposure, the RBCs decreased in size, appeared to be spike-like, and had decreased forward scatter. Inhibition of Ca²⁺ influx attenuated PS-exposure caused by 6 h Cr⁶⁺ exposure, but did not prevent 24 h Cr⁶⁺ exposure-induced morphological change in RBCs. Inhibition of rapid ATP consumption using adenine significantly ameliorated Cr⁶⁺-caused PS-exposure at 12 h, 24 h and 48 h, and prevented 24 h Cr⁶⁺ incubation-induced morphological change in RBCs. Conclusion: Cr⁶⁺ can lead to eryptosis. Ca²⁺ influx, increased ROS levels, and rapid ATP consumption are closely related to Cr⁶⁺-induced RBCs damage. Ca²⁺ influx plays an extremely important role in Cr⁶⁺-mediated toxicity.

Toward hemocompatible self-assembling antimicrobial nanofibers: understanding the synergistic effect of supramolecular structure and PEGylation on hemocompatibility

“…First, the hemolytic activity of SAANs was evaluated according to the established literature protocol 46 by co-incubation of HRBCs with peptides at varying concentrations. Hemoglobin released upon hemolysis was measured absorbance at 570 nm for quantitative comparison of the hemolytic activity of different SAANs.…”

Stimulation of Suicidal Erythrocyte Death by PRIMA-1

“…PRIMA-1 tended to increase phosphatidylserine exposure at lower concentrations (10 µM), an effect, however, not reaching statistical significance. It must be kept in mind that erythrocytes may be sensitized to the effect of PRIMA-1 by other xenobiotics stimulating cell membrane scrambling [35,49,50,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82] or by diseases associated with enhanced cell membrane scrambling, such as sepsis, malaria, sickle cell disease, Wilson's disease, iron deficiency, malignancy, metabolic syndrome, diabetes, hepatic failure, renal insufficiency, hemolytic uremic syndrome, hyperphosphatemia and phosphate depletion [34,83,84]. …”

Transcriptome reveals the overexpression of a kallikrein gene cluster (KLK1/3/7/8/12) in the Tibetans with high altitude-associated polycythemia

“…The disease affects the majority of individuals residing at a high altitude (1). More red blood cells (RBCs) are produced to carry oxygen to the lungs (2,3). The number of RBCs reaches a high level in the majority of individuals following long-term exposure to high-altitude situations.…”