2007, Vol. 49, N 1, p. 70-78
PROOXIDANT AND CYTOTOXIC ACTION OF N-ACETYLCYSTEINE AND GLUTATHIONE COMBINED WITH VITAMIN B12b

M. E. Solovieva, V. V. Soloviev, A. A. Faskhutdinova, A. A. Kudryavtsev, V. S. Akatov

Institute of Theoretical and Experimental Biophysics RAS, Pushchino, Moscow region;
e-mail: groupakatov@rambler.ru

We studied the prooxidant and cytotoxic action of thiols N-acetylcystein (NAC) and glutathione (GSH) combined with vitamin B12b. The synergism of action of the thiols and B12b resulted in human carcinoma cell damage was found. It was shown that GSH and NAC in physiological doses combined with B12b caused the initiation of apoptosis. It was established that prooxidant action of the thiols combined with vitamin B12b, 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 B12b. Therefore, the thiols GSH and NAC widely used as antioxidants, in combination with vitamin B12b show prooxidant characteristics and induce, with the participation of intracellular iron, apoptotic HEp-2 cell death.

Key words:  thiols, antioxidants, vitamin B12b, oxidative stress, apoptosis, tumor cells


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