Clofazimine Induced Suicidal Death of Human Erythrocytes

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
Arbace OfficiosoFlorian Lang

Abstract

The antimycobacterial riminophenazine clofazimine has previously been shown to up-regulate cellular phospholipase A2 and to induce apoptosis. In erythrocytes phospholipase A2 stimulates eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Phospholipase A2 is in part effective by fostering formation of prostaglandin E2, which triggers Ca(2+) entry. Stimulators of Ca(2+) entry and eryptosis further include oxidative stress and energy depletion. The present study tested, whether and how clofazimine induces eryptosis. Phosphatidylserine exposure at the cell surface was estimated from annexin V binding, cell volume from forward scatter, hemolysis from hemoglobin release, cytosolic Ca(2+) activity ([Ca(2+)]i) from Fluo3-fluorescence, reactive oxygen species (ROS) from 2', 7'-dichlorodihydrofluorescein diacetate (DCFDA) fluorescence, and cytosolic ATP level utilizing a luciferin-luciferase assay kit. A 24-48 hours exposure of human erythrocytes to clofazimine (≥ 1.5 µg/ml) significantly increased the percentage of annexin-V-binding cells without appreciably modifying forward scatter. Clofazimine significantly increased [...Continue Reading

Citations

Jan 18, 2016·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Arbace OfficiosoCaterina Manna
Jun 14, 2016·Cell Biochemistry and Function·Elena SignorettoFlorian Lang
Nov 1, 2016·The Journal of Antimicrobial Chemotherapy·Moloko C CholoRonald Anderson
Feb 20, 2017·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Majed AbedAlfred Königsrainer
Feb 22, 2017·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Mustafa AlmasryCaterina Faggio
May 26, 2017·International Journal of Cancer. Journal International Du Cancer·Elisabeth LangFlorian Lang

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