Ebselen decreases oxygen free radical production and iron concentrations in the hearts of chronically iron-overloaded mice.
Chronic iron overload is a major cause of cardiac failure throughout the world, but its pathogenesis remains to be clarified. It is conjectured that the toxicity of iron is due to its ability to catalyze the formation of oxygen free radicals (OFR), which can damage cellular membranes, proteins, and DNA. The authors report on the cardioprotective effects of the glutathione peroxidase (GPx) mimic ebselen on iron concentrations in the heart and GPx activity, and on the production of the cytotoxic aldehydes hexanal, 4-hydroxyl-2-nonenal (HNE), and malondialdehyde (MDA). Fifteen B6D2F1 mice were randomized to 1 of 3 treatment groups for a total of 20 treatments: 1) control (0.1 mL normal saline i.p. per mouse, per day); 2) iron-only (10 mg iron dextran i.p. per mouse, per day); 3) iron plus ebselen (25 mg/kg p.o. per mouse, per day). In comparison to iron-only treated mice, the authors' findings show that supplementation with ebselen can decrease both cytotoxic aldehyde and iron concentrations in heart tissue. Additionally, mice supplemented with ebselen had an increase in GPx activity level in comparison to iron-only treated mice. To the authors' knowledge, this is the first study to examine the cardioprotective effects of ebselen against OFR damage in a model of chronic iron overload. These findings suggest that ebselen may have significance in the management of disorders of iron overload.
Davis
Matthew T
MT
School of Nursing at Queen's University, Kingston, ON, Canada.
Bartfay
Wally J
WJ
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001393:Azoles / Q000494:pharmacology / Q000627:therapeutic use*; D009202:Cardiomyopathies / Q000139:chemically induced* / Q000378:metabolism; D002908:Chronic Disease; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005609:Free Radicals / Q000009:adverse effects / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000032:analysis / Q000187:drug effects / Q000378:metabolism; D007501:Iron / Q000032:analysis / Q000378:metabolism; D019190:Iron Overload / Q000150:complications / Q000378:metabolism / Q000517:prevention & control*; D054833:Isoindoles; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism; D016566:Organoselenium Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D017382:Reactive Oxygen Species / Q000009:adverse effects / Q000378:metabolism
D000975:Antioxidants; D001393:Azoles; D016861:Cyclooxygenase Inhibitors; D005609:Free Radicals; D054833:Isoindoles; D016566:Organoselenium Compounds; D017382:Reactive Oxygen Species; C042986:ebselen; D007501:Iron; D005979:Glutathione Peroxidase