Transition-Metal Mediated Free Radical Formation in Vitro and IN Vivo

Kadiiska, M.

Abstract

Increasing evidence indicates that probably most acute and chronic metal poisoning involve free radical reactions in tissue injury. Since the concentration of radicals occurring in body tissues is generally near the sensitivity limit of ESR spectroscopy, the spin trapping technique is used. The manipulation of an animal model also provides evidence that the toxicity is indeed free radical mediated. By successfully applying this approach, ESR evidence has been obtained for free radical formation generated by iron may occur in vivo not only after acute but also after chronic iron intake. Chromium (VI) compounds pose a serious occupational health hazard in terms of both their potential respiratory tract carcinogenicity and their toxic effect on other organs. By applying ESR and a spin trapping technique, the existence of a radical adduct has also been shown in bile of rats after acute Cr(VI) poisoning. Additional measurements are carried out to provide more data about the exact mechanism by which the detected free radicals from Cr(VI) intoxication are formed. We were not able to show free radical formation in bile or in different tissues (brain, liver, kidneys) after poisoning of rats with lead or with aminolevulinic acid. We also found lack of toxic synergistic effects of Pb and Fe or Al and Fe after these acute metal-metal poisonings.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Environmental Health Sciences (NIEHS)
• Type: Intramural Research (Z01)
• Project #: 1Z01ES050117-04
• Application #: 3755454
• Support Year: 4
• Fiscal Year: 1994

Institution

• Name: National Institute of Environmental Health Sciences
• Country: United States

Publications

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

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

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

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