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Stimulation of Suicidal Erythrocyte Death by Ribavirin
Author(s) -
Oswald Gergely,
Alzoubi Kousi,
Abed Majed,
Lang Florian
Publication year - 2014
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12165
Subject(s) - phosphatidylserine , ribavirin , haemolysis , annexin , extracellular , apoptosis , cytosol , stimulation , chemistry , pharmacology , cytochrome c , red blood cell , biology , medicine , biochemistry , hepatitis c virus , immunology , virus , enzyme , membrane , phospholipid
Ribavirin is widely used in the treatment for viral disease such as chronic viral hepatitis. Side effects limiting the use of the drug include haemolytic anaemia. If challenged by stimulators of haemolysis, erythrocytes may enter suicidal death or eryptosis, thus preventing the release of haemoglobin into circulating blood. Eryptosis is characterized by cell shrinkage and by cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Eryptosis may be triggered by increase in cytosolic Ca 2+ activity ([Ca 2+ ] i ). This study explored whether ribavirin modifies [Ca 2+ ] i and elicits eryptosis. Cell volume has been estimated from forward scatter, phosphatidylserine abundance at the erythrocyte surface from annexin V binding, haemolysis from haemoglobin release and [Ca 2+ ] i from Fluo‐3 fluorescence. A 48‐hr exposure to ribavirin (≥8 μg/ml) was followed by a significant increase in [Ca 2+ ] i , a significant decrease in forward scatter and a significant increase in annexin V binding. The annexin V binding after ribavirin treatment was significantly blunted but not abolished in the nominal absence of extracellular Ca 2+ . In conclusion, ribaverin stimulates eryptosis, an effect at least in part due to entry of extracellular Ca 2+ .