Mechanism of erythrocyte death in human population exposed to arsenic through drinking water.
Arsenic contamination in drinking water is one of the biggest natural calamities, which has become an imperative threat to human health throughout the world. Abbreviation of erythrocyte lifespan leading to the development of anemia is a common sequel in arsenic exposed population. This study was undertaken to explore the mechanism of cell death in human erythrocytes during chronic arsenic exposure. Results revealed transformation of smooth discoid red cells into evaginated echinocytic form in the exposed individuals. Further distortion converted reversible echinocytes to irreversible spheroechinocytes. Arsenic toxicity increased membrane microviscosity along with an elevation of cholesterol/phospholipid ratio, which hampered the flexibility of red cell membrane and made them less deformable. Significant increase in the binding of merocyanine 540 with erythrocyte membrane due to arsenic exposure indicated disruption of lipid packing in the outer leaflet of the cell membrane resulting from altered transbilayer phospholipid asymmetry. Arsenic induced eryptosis was characterized by cell shrinkage and exposure of phosphatidylserine at the cell surface. Furthermore, metabolic starvation with depletion of cellular ATP triggered apoptotic removal of erythrocytes from circulation. Significant decrease in reduced glutathione content indicating defective antioxidant capacity was coupled with enhancement of malondialdehyde and protein carbonyl levels, which pointed to oxidative damage to erythrocyte membrane. Arsenic toxicity intervened into red cell membrane integrity eventually leading to membrane destabilization and hemoglobin release. The study depicted the involvement of both erythrophagocytosis and hemolysis in the destruction of human erythrocytes during chronic arsenic exposure.
Biswas
Debabrata
D
Cell Biology and Physiology Division, Indian Institute of Chemical Biology, Kolkata, India.
Banerjee
Mayukh
M
Sen
Gargi
G
Das
Jayanta K
JK
Banerjee
Apurba
A
Sau
T J
TJ
Pandit
Sudipta
S
Giri
A K
AK
Biswas
Tuli
T
D000328:Adult; D000740:Anemia / Q000209:etiology; D017304:Annexin A5 / Q000187:drug effects* / Q000378:metabolism; D001151:Arsenic / Q000009:adverse effects* / Q000032:analysis / Q000652:urine; D004910:Erythrocyte Membrane / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006461:Hemolysis / Q000187:drug effects*; D006801:Humans; D007194:India; D008297:Male; D010718:Phosphatidylserines / Q000378:metabolism*; D014874:Water Pollutants, Chemical / Q000009:adverse effects* / Q000032:analysis / Q000652:urine
D017304:Annexin A5; D010718:Phosphatidylserines; D014874:Water Pollutants, Chemical; D001151:Arsenic