TitleThiourea protects against copper-induced oxidative damage by formation of a redox-inactive thiourea-copper complex.
Publication TypeJournal Article
Year of Publication2002
AuthorsZhu B-Z, Antholine WE, Frei B
JournalFree Radic Biol Med
Date Published2002 Jun 15
KeywordsAnimals, Ascorbic Acid, Cattle, Copper, DNA Damage, Dose-Response Relationship, Drug, Electron Spin Resonance Spectroscopy, Free Radical Scavengers, Histidine, Hydrogen Peroxide, Hydroxyl Radical, Oxidation-Reduction, Oxidative Stress, Phenanthrolines, Serum Albumin, Bovine, Thiourea

Although thiourea has been used widely to study the role of hydroxyl radicals in metal-mediated biological damage, it is not a specific hydroxyl radical scavenger and may also exert antioxidant effects unrelated to hydroxyl radical scavenging. Thus, we investigated the effects of thiourea on copper-induced oxidative damage to bovine serum albumin (1 mg/ml) in three different copper-containing systems: Cu(II)/ascorbate, Cu(II)/H(2)O(2), and Cu(II)/H(2)O(2)/ascorbate [Cu(II), 0.1 mM; ascorbate, 1 mM; H(2)O(2), 1 mM]. Oxidative damage to albumin was measured as protein carbonyl formation. Thiourea (0.1-10 mM) provided marked and dose-dependent protection against protein oxidation in all three copper-containing systems. In contrast, only minor protection was observed with dimethyl sulfoxide and mannitol, even at concentrations as high as 100 mM. Strong protection was also observed with dimethylthiourea, but not with urea or dimethylurea. Thiourea also significantly inhibited copper-catalyzed oxidation of ascorbate, and competed effectively with histidine and 1,10-phenanthroline for binding of cuprous, but not cupric, copper, as demonstrated by both UV-visible and low temperature electron spin resonance measurements. We conclude that the protection by thiourea against copper-mediated protein oxidation is not through scavenging of hydroxyl radicals, but rather through the chelation of cuprous copper and the formation of a redox-inactive thiourea-copper complex.

Alternate JournalFree Radic. Biol. Med.
PubMed ID12057771
Grant ListAT00066 / AT / NCCIH NIH HHS / United States
ES00210 / ES / NIEHS NIH HHS / United States
ES11497 / ES / NIEHS NIH HHS / United States
HL60886 / HL / NHLBI NIH HHS / United States
RR01008 / RR / NCRR NIH HHS / United States