Generation of free radical by interaction of iron with thiols in human plasma and its possible significance.
It has been reported that iron can generate reactive oxygen species (ROS) with thiols. In this study, we examined the interaction of iron with thiols in plasma and the generation of ROS. In human plasma, unlike with Fe(3+), treatment with Fe(2+) increased lucigenin-enhanced chemiluminescence in a concentration-dependent manner, and this was inhibited by superoxide dismutase. Boiling of plasma did not affect chemiluminescence generation induced by Fe(2+). Thiol depletion in plasma by pretreatment with N-ethylmaleimide (NEM) decreased chemiluminescence significantly. Consistent with these findings, albumin, the major thiol contributor in plasma, also generated ROS with Fe(2+). Treatment with Fe(2+) resulted in significant reduction of oxygen radical absorbance capacity (ORAC value) in plasma followed by an increase in low-density lipoprotein (LDL) oxidation. These results suggest that generation of ROS by nonenzymatic reaction of Fe(2+) with plasma thiols could lead to reduction of total antioxidant capacity in plasma, thereby enhancing susceptibility of plasma LDL to oxidation under iron overload conditions.
Chung
Ka-Young
KY
Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea.
Lee
Seung-Jin
SJ
Chung
Seung-Min
SM
Lee
Moo-Yeol
MY
Bae
Ok-Nam
ON
Chung
Jin-Ho
JH
D000293:Adolescent; D000328:Adult; D001769:Blood / Q000378:metabolism*; D005609:Free Radicals / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism* / Q000494:pharmacology; D019190:Iron Overload / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008163:Luminescent Measurements; D008297:Male; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism; D012709:Serum Albumin / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism*
D005609:Free Radicals; D008077:Lipoproteins, LDL; D017382:Reactive Oxygen Species; D012709:Serum Albumin; D013438:Sulfhydryl Compounds; D007501:Iron