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The initiation of eryptosis as a result of genotoxic action of Cr(VI), seen through micronucleus and comet assay in the peripheral erythrocytes of Ctenopharyngodon idellus was evaluated through RT-qPCR. For this, fish was exposed to sublethal concentration of hexavalent chromium (5.30 and 10.63 mg/L), and the blood was sampled on different endpoints (15, 30 and 45 days). Accumulation of chromium in the erythrocytes was also studied, which depicted a significant increase in toxicant concentration and time dependent manner. Both concentrations of hexavalent chromium induced DNA damage, visible in the form of comet tails. The presence of micronuclei in the erythrocytes was accompanied with occurrence of nuclear bud (NBu), lobed nucleus (Lb), notched nucleus (Nt), vacuolated nucleus (Vn), binucleated cell (Bn) as nuclear abnormalities; and acanthocytes (Ac), echinocytes (Ec), notched cells (Nc), microcytes (Mc) and vacuolated cytoplasm (Vc) as cytoplasmic abnormalities. The expression of genes related to intrinsic apoptotic pathway induced by Cr(VI) presented significant (p < 0.05) upregulation in the expression of p53, Bax, Apaf-1, caspase9 and caspase3, and downregulation of Bcl2; inferring the initiation of apoptotic pathway. The ration of Bax and Bcl2 also appended the apoptotic state of the erythrocytes. From the present investigation, it can be concluded that genotoxicity induced by hexavalent chromium lead to eryptosis in C. idellus., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

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 of chemotherapy is anemia, which may result from direct erythrocyte hemolysis or premature cell death known as eryptosis. Similar to nucleated cells, eryptotic cells lose membrane asymmetry and Ca 2+ regulation, and undergo oxidative stress, shrinkage, and activation of a host of kinases. In this report, we sought to examine the hemolytic and eryptotic potential of TCS and dissect the underlying mechanistic scenarios involved there in. Hemolysis was spectrophotometrically evaluated by the degree of hemoglobin release into the medium. Flow cytometry was utilized to detect phosphatidylserine (PS) exposure by annexin-V binding, intracellular Ca 2+ by Fluo-3/AM fluorescence, and oxidative stress by 2-,7-dichlorodihydrofluorescin diacetate (DCFH 2 -DA). Incubation of cells with 10-100 μM TCS for 1-4 h induced time- and dose-dependent hemolysis. Moreover, TCS significantly increased the percentage of eryptotic cells as evident by PS exposure (significantly enhanced annexin-V binding). Interestingly, TCS-induced eryptosis was preceded by elevated intracellular Ca 2+ levels but was not associated with oxidative stress. Cotreatment of erythrocytes with 50 μM TCS and 50 μM SB203580 (p38 MAPK inhibitor), or 300 μM necrostatin-1 (receptor-interacting protein 1 (RIP1) inhibitor) significantly ameliorated TCS-induced PS externalization. We conclude that TCS is cytotoxic to erythrocytes by inducing hemolysis and stimulating premature death at least in part through Ca 2+ mobilization, and p38 MAPK and RIP1 activation., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Brominated flame retardants (BFRs) such as tetrabromobisphenol A (TBBPA) and tetrabromobisphenol S (TBBPS) as well as bromophenols, i.e. 2,4-dibromophenol (2,4-DBP), 2,4,6-tribromophenol (2,4,6-TBP) and pentabromophenol (PBP) have raised wide concerns due to their widespread occurrence in the environment and adverse effects observed in living organisms including human. The effect of BFRs on apoptosis of human erythrocytes has not been examined, that is why we have decided to assess eryptotic potential of these substances by determining changes in phosphatidylserine (PS) translocation, alterations in intracellular ROS and calcium ion levels, as well as caspase-3 and calpain activation in this cell type. It has been found that all BFRs studied even in the concentration of 0.001 μg/mL induced ROS formation. The compounds examined caused apoptosis by PS externalization and caspase-3 activation in human red blood cells. It has also been shown that calcium ions and calpain did not play a significant role in eryptosis induction by BFRs studied in human erythrocytes., (Copyright © 2018. Published by Elsevier Ltd.)

Phthalates have been extensively used as plasticizers in various fields, including food, cosmetic, and pharmaceutical industry. Those compounds do not form covalent bonds to substances they are being added to, and thus they may migrate easily and penetrate various products used every day. They may reach organisms with air, food, or by a direct skin contact. Significant levels of phthalates and their metabolites are found in urine, breast milk, blood serum, venous blood, and cord blood. The purpose of this study was to assess the simple toxicity (haemolysis) and programmed death (eryptosis) caused by following phthalates: di-n-butyl phthalate (DBP), butylbenzyl phthalate (BBP) and their metabolites: mono-n-butyl phthalate (MBP) and mono-benzyl phthalate (MBzP) in vitro in human RBCs. RBCs were incubated with the above mentioned compounds at concentrations ranging between 0.5 and 500 μg/mL for 24 h. Obtained results demonstrated that DBP and BBP possess higher haemolytic properties compared to their metabolites. The lethal concentration (LC 50 ) was determined. The value was 126.37 ± 5.94 μg/mL for DBP, and 103.65 ± 4.03 μg/mL for BBP, and for metabolites the LC 50 value was over 500 μg/mL. All compounds induced eryptosis causing translocation of phosphatidylserine, increased cytosolic calcium ions level, increased caspase-3 and calpain activation in human erythrocytes. BBP caused translocation of phosphatidylserine at a lower concentration compared to DBP. In case of other parameters, more pronounced changes were evoked by DBP at lower concentrations. Metabolites showed a significantly lower toxicity compared to parent compounds., (Copyright © 2018 Elsevier Ltd. All rights reserved.)