Non-ionic contrast media induces oxidative stress and apoptosis through Ca²⁺ influx in human neutrophils.
Non-ionic contrast media (CM) can induce tissue kidney injury via activation of phagocytosis and oxidative stress, although the mechanisms of injury via neutrophils are not clear. We investigated the effects of CM on oxidative stress and Ca²⁺ concentrations in serum and neutrophils of humans. Ten migraine patients were used in the study. Serum and neutrophil samples from patients' peripheral blood were obtained before (control) and 30 min after non-ionic (iopromide) CM injection. The neutrophils were incubated with non specific transient receptor potential 2 (TRPM2) channel blocker, 2-aminoethoxydiphenyl borate (2-APB), and voltage gated Ca²⁺ channel blockers, verapamil plus diltiazem. Serum and neutrophil lipid peroxidation, apoptosis and intracellular Ca²⁺ concentrations levels were higher in the CM group than in controls. The neutrophilic reduced glutathione (GSH) and glutathione peroxidase (GSH-Px) levels as well as serum vitamin E and β-carotene concentrations were lower in the CM group than in controls. Neutrophil lipid peroxidation levels were lower in the CM+2-APB and CM+verapamil-diltiazem groups than in the CM group, although GSH, GSH-Px and intracellular Ca²⁺ values increased in the CM+2-APB and CM+verapamil-diltiazem groups. However, caspase-3, caspase-9, vitamin A and vitamin C values were unaltered by CM treatment. In conclusion, we observed that CM induced oxidative stress and Ca²⁺ influx by decreasing vitamin E, β-carotene and Ca²⁺ release levels in human serum and neutrophils. However, we observed protective effects of Ca²⁺ channel blockers on Ca²⁺ influx in neutrophils.
Department of Radiology, Faculty of Medicine, Süleyman Demirel University, Isparta, Turkey.
Mustafa
M
Kayan
Mustafa
M
Nazıroğlu
Ishak Suat
IS
Ovey
Mehmet
M
Aykur
Abdülhadi Cihangir
AC
Uğuz
Vedat Ali
VA
Yürekli
D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D001896:Boron Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D003287:Contrast Media / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology; D005260:Female; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D007472:Iohexol / Q000031:analogs & derivatives* / Q000494:pharmacology; D017136:Ion Transport / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000378:metabolism / Q000473:pathology; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D050053:TRPM Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology; D014810:Vitamin E / Q000378:metabolism; D019207:beta Carotene / Q000378:metabolism
D001896:Boron Compounds; D002121:Calcium Channel Blockers; D003287:Contrast Media; D050053:TRPM Cation Channels; C121934:TRPM2 protein, human; D019207:beta Carotene; D014810:Vitamin E; D007472:Iohexol; C038192:iopromide; D014700:Verapamil; C109986:2-aminoethoxydiphenyl borate; D005979:Glutathione Peroxidase; D020169:Caspases; D004110:Diltiazem; D005978:Glutathione; D002118:Calcium