Disruption of erythrocyte membrane asymmetry by triclosan is preceded by calcium dysregulation and p38 MAPK and RIP1 stimulation

摘要: Abstract Triclosan (TCS) is a broad-spectrum antimicrobial used in personal care products, household items, and medical devices. Owing to its apoptotic potential against tumor cells, TCS has been proposed for the treatment of malignancy. A major complication chemotherapy anemia, which may result from direct erythrocyte hemolysis or premature cell death known as eryptosis. Similar nucleated eryptotic cells lose membrane asymmetry Ca2+ regulation, undergo oxidative stress, shrinkage, activation host kinases. In this report, we sought examine hemolytic dissect underlying mechanistic scenarios involved there in. Hemolysis was spectrophotometrically evaluated by degree hemoglobin release into medium. Flow cytometry utilized detect phosphatidylserine (PS) exposure annexin-V binding, intracellular Fluo-3/AM fluorescence, stress 2-,7-dichlorodihydrofluorescin diacetate (DCFH2-DA). Incubation with 10–100 μM 1–4 h induced time- dose-dependent hemolysis. Moreover, significantly increased percentage evident PS (significantly enhanced binding). Interestingly, TCS-induced eryptosis preceded elevated levels but not associated stress. Cotreatment erythrocytes 50 μM SB203580 (p38 MAPK inhibitor), 300 μM necrostatin-1 (receptor-interacting protein 1 (RIP1) inhibitor) ameliorated externalization. We conclude that cytotoxic inducing stimulating at least part through mobilization, p38 RIP1 activation.