Conflicting effects of N-acetylcysteine on purified neurons derived from rat cortical culture.
We examined the protective effects of N-acetylcysteine (NAC) on the death of glia-free neurons in culture. Under normoxic conditions, the protection by NAC was observed only in cystine-free but not complete medium. When the cells were cultured under hypoxic conditions, NAC much elongated their survival even in the presence of cystine. H2O2 was found to be generated to considerable concentration in the presence of both NAC and cystine, and the administration of catalase prevented the cell death. These results suggest that the harmful effect of NAC is because of H2O2 generated by autoxidation of cysteine, which derives from the reaction between NAC and cystine. The present results raise the possibility that NAC can act as either antioxidant or prooxidant depending on the milieu.
Sagara
Jun-Ichi
J
Center for Medical Sciences, Ibaraki Prefectural University of Health Sciences, Japan. sagara@ipu.ac.jp
Bannai
Shiro
S
Shikano
Naoto
N
Makino
Nobuo
N
D000111:Acetylcysteine / Q000627:therapeutic use / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use / Q000633:toxicity*; D018929:Cell Culture Techniques; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D051381:Rats
D000975:Antioxidants; D018696:Neuroprotective Agents; D000111:Acetylcysteine