Pb-Induced Eryptosis May Provoke Thrombosis Prior to Hemolysis

Abstract

Lead (Pb) is a common metal, which can be toxic to the human body via the pollution of water or food, and can cause anemia and other diseases. However, what happens before hemolysis and anemia caused by Pb poisoning is unclear. Here, we demonstrated Pb can cause procoagulant activity of erythroid cells leading to thrombosis before hemolysis. In freshly isolated human erythroid cells, we observed that Pb resulted in hemolysis in both concentration- and time-dependent manners, but that no lysis occurred in Pb-exposed erythroid cells (≤20 μM for 1 h). Pb treatment did not cause shape changes at up to 0.5 h incubation but at 1 h incubation echinocyte and echino-spherocyte shape changes were observed, indicating that Pb can exaggerate a concentration- and time-dependent trend of shape changes in erythroid cells. After Pb treatment, ROS-independent eryptosis was shown with no increase of reactive oxygen species (ROS), but with an increase of [Ca2+]i and caspase 3 activity. With a thrombosis mouse model, we observed increased thrombus by Pb treatment (0 or 25 mg/kg). In brief, prior to hemolysis, we demonstrated Pb can cause ROS-independent but [Ca2+]i-dependent eryptosis, which might provoke thrombosis.

Hemocompatibility of dextran-graft-polyacrylamide/zinc oxide nanosystems: hemolysis or eryptosis?

“…Thus, it can be postulated that eryptosis should be triggered by lower concentrations of xenobiotics compared with hemolysis. Indeed, xenobiotics-induced eryptosis is shown to precede hemolysis in multiple studies [44,[73][74][75][76][77]. This hypothesis is also supported by some nanotoxicological studies for Fe 3 O 4 magnetic NPs [44] or polyvinylpyrrolidone-and citrate-coated silver NPs [43].…”

Serum levels of lead are associated with venous thromboembolism: a retrospective study based on the NHANES database (1999 to 2018)

“…Since no evidence of etiology was found, the authors presumed that chronic lead exposure might be the reason of the thrombosis ( 18 ). Later in an experimental study, Jin et al demonstrated lead can cause reactive oxygen species -independent but [Ca 2+ ] i -dependent eryptosis, which might provoke thrombosis ( 19 ). However, to date, there have been no studies analyzing the relationship between the levels of lead in the blood and VTE.…”