Although free radical formation is known to occur from cooper in Fenton- like reactions in vitro, free radicals from copper have not been detected in living animals until now. By applying ESR and the secondary radical spin trapping technique, evidence for hydroxyl radical formation in vivo was obtained in rats treated simultaneously with copper and ascorbic acid. The existence of hydroxyl radical has also been shown in the file of selenium- and vitamin E-deficient rats during conditions of acute copper overload. We demonstrate that hydroxyl radical generated by copper can indeed occur in vivo and contribute to oxidative damage, though in our model of copper-intoxicated rats copper alone does not cause the formation of detectable radical adducts. Paraquat is a toxin whose toxicity is attributed to its ability to generate the superoxide radical anion. Increased superoxide production can in turn stimulate hydroxyl radical formation in vitro and in vivo from metal ions. We have shown this to be true for both copper and iron overload experiments in rats. Some metal ions may also have beneficial effects on free radical metabolites in vivo. Our results show a suppression of free radical metabolites detected in rats from the metabolism of the hepatotoxin carbon tetrachloride due to pretreatment with trivalent chromium. The formation of artifactual radical adducts in spin trapping experiments is a possibility that must always be guarded against. We have demonstrated experimental procedures necessary to inhibit ex vivo metal ion-induced free radical chemistry in cases of metal overload. This is crucial for correctly identifying radicals generated in vivo. We have established certain criteria for suppressing artifactual ESR signals in vitro resulting from non-radical chemistry of the spin trap DMPO in the presence of copper and iron ions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES050117-02
Application #
3841110
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
1992
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
Liu, Jie; Qian, Steven Y; Guo, Qiong et al. (2008) Cadmium generates reactive oxygen- and carbon-centered radical species in rats: insights from in vivo spin-trapping studies. Free Radic Biol Med 45:475-81
Woods, Courtney G; Burns, Amanda M; Maki, Akira et al. (2007) Sustained formation of alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone radical adducts in mouse liver by peroxisome proliferators is dependent upon peroxisome proliferator-activated receptor-alpha, but not NADPH oxidase. Free Radic Biol Med 42:335-42
Jiang, JinJie; Corbett, Jean; Hogg, Neil et al. (2007) An electron paramagnetic resonance investigation of the oxygen dependence of the arterial-venous gradient of nitrosyl hemoglobin in blood circulation. Free Radic Biol Med 43:1208-15
Zhong, Zhi; Connor, Henry D; Li, Xiangli et al. (2006) Reduction of ciclosporin and tacrolimus nephrotoxicity by plant polyphenols. J Pharm Pharmacol 58:1533-43
Nakai, Kozo; Kadiiska, Maria B; Jiang, Jin-Jie et al. (2006) Free radical production requires both inducible nitric oxide synthase and xanthine oxidase in LPS-treated skin. Proc Natl Acad Sci U S A 103:4616-21
Kono, Hiroshi; Woods, Courtney G; Maki, Akira et al. (2006) Electron spin resonance and spin trapping technique provide direct evidence that edaravone prevents acute ischemia-reperfusion injury of the liver by limiting free radical-mediated tissue damage. Free Radic Res 40:579-88
Arimoto, Toyoko; Kadiiska, Maria B; Sato, Keizo et al. (2005) Synergistic production of lung free radicals by diesel exhaust particles and endotoxin. Am J Respir Crit Care Med 171:379-87
Zhong, Zhi; Connor, Henry D; Froh, Mattias et al. (2005) Free radical-dependent dysfunction of small-for-size rat liver grafts: prevention by plant polyphenols. Gastroenterology 129:652-64
Yue Qian, Steven; Kadiiska, Maria B; Guo, Qiong et al. (2005) A novel protocol to identify and quantify all spin trapped free radicals from in vitro/in vivo interaction of HO(.-) and DMSO: LC/ESR, LC/MS, and dual spin trapping combinations. Free Radic Biol Med 38:125-35
Kadiiska, M B; Ghio, A J; Mason, R P (2004) ESR investigation of the oxidative damage in lungs caused by asbestos and air pollution particles. Spectrochim Acta A Mol Biomol Spectrosc 60:1371-7

Showing the most recent 10 out of 30 publications