Eryptosis triggered by bismuth

Abstract

Bismuth is used for multiple industrial purposes and in the treatment of several gastrointestinal diseases. Untoward effects of bismuth include anemia, which could, in theory, result from suicidal erythrocyte death or eryptosis. Hallmarks of eryptosis are cell shrinkage and cell membrane scrambling with phosphatidylserine exposure at the cell surface. Phosphatidylserine-exposing cells are rapidly cleared from circulating blood. Signaling leading to eryptosis includes increase in cytosolic Ca(2+) activity and formation of ceramide. The present experiments explored whether bismuth elicits eryptosis. To this end, phosphatidylserine exposure was estimated from annexin V-binding, cell shrinkage from decrease of forward scatter in FACS analysis, cytosolic Ca(2+) activity from Fluo3 fluorescence and ceramide abundance from binding of fluorescent antibodies. A 48 h exposure to bismuth (> or =500 microg/l BiCl(3)) enhanced the percentage of annexin V-binding cells and decreased forward scatter, increased cytosolic Ca(2+) activity, and stimulated ceramide formation. In conclusion, bismuth stimulates eryptosis, the suicidal death of erythrocytes. The effect may contribute to or even account for the development of anemia during bismuth treatment. Moreover, ceramide formation in intestinal cells may participate in the therapeutic efficacy of bismuth preparations.

Hemin-induced suicidal erythrocyte death

“…Some of these diseases may cause eryptosis by stimulating the formation of hemin. Furthermore, several eryptosis-triggering xenobiotics and endogeneous substances have been identified, such as cordycepin [50], methylglyoxal [54], amyloid peptides [53], lipopetides [71] retinoic acid [55], paclitaxel [44], amantadine [23], chlorpromazine [1], ciglitazone [58], cyclosporine [56], Bay-5884 [65], curcumin [4], valinomycin [64], listeriolysin [25], aluminum [57], copper [46], bismuth [13], tin [52], cadmium [68], selenium [67], vanadate [27], gold [69], and arsenic [51]. At least in theory, some of those substances may be effective through stimulation of hemin formation.…”

Patulin-Induced Suicidal Erythrocyte Death

“…Eryptosis is stimulated by a wide variety of xenobiotics including several food contaminants [16,22,23,24,25,25,26,27,28,29,30,31,32,33,34,35,36]. Moreover, eryptosis is observed in several clinical disorders [7], such as diabetes [20,37,38], renal insufficiency [39], hemolytic uremic syndrome [40], sepsis [41], sickle cell disease [42], malaria [43,44,45,46,47], Wilson's disease [47], iron deficiency [48], phosphate depletion [49], and presumably metabolic syndrome [50].…”

Inhibitory Effect of Thymol on Suicidal Erythrocyte Death

“…Moreover, eryptosis may be triggered by a wide variety of endogeneous substances and xenobiotics, such as antiA IgG antibodies [24], cordycepin [25], hemin [26], amiodarone [27], methylglyoxal [28], amyloid peptides [29], anandamide [30], lipopetides [31] retinoic acid [32], paclitaxel [33], amantadine [34], chlorpromazine [35], ciglitazone [36]. cyclosporine [37], Bay-5884 [38], curcumin [39], valinomycin [40], listeriolysin [41], aluminium [42], bismuth [43], mercury [44], copper [23], cadmium [45], selenium [46], vanadate [47], gold [48] and arsenic [49]. Inhibitors of eryptosis include caffeine [50].…”