Antioxidant role of N-acetyl cysteine isomers following high dose irradiation.
High dose, acute radiation exposure, as in radiation accidents, induces three clinical syndromes that reflect consequences of oxidative protein, lipid, and DNA damage to tissues such as intestine, lung, and liver. In the present study, we irradiated C57BL/6 mice with 18 Gy whole-body radiation (XRT) and evaluated N-acetyl cysteine (NAC) isomers LNAC and DNAC as potential radioprotectors under conditions that would model the gastrointestinal syndrome. We focused on tissues thought not immediately involved in the gastrointestinal syndrome. Both LNAC and DNAC protected the lung and red blood cells (RBC) from glutathione (GSH) depletion following radiation exposure. However, only LNAC also supplemented the spleen GSH levels following XRT. Protection from increased malondialdehyde (MDA) levels (lung) and increased 8-hydroxy-deoxyguanosine (8-oxo-dG) presence (liver) following XRT was observed with treatment by either isomer of NAC. These results imply that either NAC isomer can act as a radioprotectant against many aspects of oxidative damage; chirality is only important for certain aspects. This pattern would be consistent with direct action of NAC in many radioprotection and repair processes, with a delimited role for NAC in GSH synthesis in some aspects of the problem.
Neal
Rachel
R
Department of Chemistry, University of Missouri at Rolla, Rolla, MO, USA. nercal@umr.edu
Matthews
Richard H
RH
Lutz
Paula
P
Ercal
Nuran
N
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000111:Acetylcysteine / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004912:Erythrocytes / Q000378:metabolism / Q000528:radiation effects; D054477:Glutaredoxins; D005978:Glutathione / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D007536:Isomerism; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects*; D008297:Male; D008315:Malondialdehyde / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D016877:Oxidants / Q000494:pharmacology; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000378:metabolism; D011490:Protein Disulfide Reductase (Glutathione); D011833:Radiation Injuries, Experimental / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000494:pharmacology; D014916:Whole-Body Irradiation
D000975:Antioxidants; D054477:Glutaredoxins; D016877:Oxidants; D011837:Radiation-Protective Agents; D008315:Malondialdehyde; D000080242:8-Hydroxy-2'-Deoxyguanosine; D010088:Oxidoreductases; D002374:Catalase; D005980:Glutathione Reductase; D011490:Protein Disulfide Reductase (Glutathione); D003849:Deoxyguanosine; D005978:Glutathione; D000111:Acetylcysteine