[Prooxidant and cytotoxic action of N-acetylcysteine and glutathione combined with vitamin Bl2b].
We studied the prooxidant and cytotoxic action of thiols N-acetylcystein (NAC) and glutathione (GSH) combined with vitamin Bl2b. The synergism of action of the thiols and Bl2b resulted in human carcinoma cell damage was found. It was shown that GSH and NAC in physiological doses combined with Bl2b caused the initiation of apoptosis. It was established that prooxidant action of the thiols combined with vitamin Bl2b, i. e. generation and accumulation of hydrogen peroxide in culture medium, led to intracellular oxidative stress and injury of cell redox system. These effects were completely abolished by nonthiol antioxidants catalase and pyruvate. The chelators of iron phenanthroline and deferoxamine did not suppress the H2O2 accumulation in culture medium but significantly inhibited the cell death induced by the thiols combined with Bl2b. Therefore, the thiols GSH and NAC widely used as antioxidants, in combination with vitamin Bl2b show prooxidant characteristics and induce, with the participation of intracellular iron, apoptotic HEp-2 cell death.
Solov'eva
M E
ME
Solov'ev
V V
VV
Faskhutdinova
A A
AA
Kudriavtsev
A A
AA
Akatov
V S
VS
D000111:Acetylcysteine / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002374:Catalase / Q000494:pharmacology; D045744:Cell Line, Tumor; D002468:Cell Physiological Phenomena / Q000187:drug effects*; D003676:Deferoxamine / Q000494:pharmacology; D004357:Drug Synergism; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005978:Glutathione / Q000494:pharmacology*; D006801:Humans; D058085:Iron Compounds / Q000494:pharmacology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D010618:Phenanthrolines / Q000494:pharmacology; D019289:Pyruvic Acid / Q000494:pharmacology; D017262:Siderophores / Q000494:pharmacology; D014805:Vitamin B 12 / Q000494:pharmacology*
D000975:Antioxidants; D016166:Free Radical Scavengers; D058085:Iron Compounds; D010618:Phenanthrolines; D017262:Siderophores; D019289:Pyruvic Acid; D002374:Catalase; D005978:Glutathione; D003676:Deferoxamine; D014805:Vitamin B 12; D000111:Acetylcysteine