Prooxidant and cytotoxic action of N-acetylcysteine and glutathione in combinations with vitamin B12b

Hydroxycobalamin catalyzes the oxidation of diethyldithiocarbamate and increases its cytotoxicity independently of copper ions

“…It has been found earlier that the oxidation of thiols in the presence of HOCbl is accompanied by the generation of hydrogen peroxide [6] , [7] , [8] . In addition, there is evidence that DDC can be oxidized by H 2 O 2 [43] .…”

“…We have previously shown that hydroxycobalamin (a form of vitamin B 12 , HOCbl), in combination with the antioxidant thiols GSH, NAC, and DTT is capable of catalyzing the formation of hydrogen peroxide at concentrations up to 30–250 μM. This catalysis considerably enhances the cytotoxic action of these classical thiol compounds and leads to the manifestation of the prooxidant action of DTT, GSH, and NAC [7] , [8] .…”

Glutathione-Redox Balance Regulates c-rel–Driven IL-12 Production in Macrophages: Possible Implications in Antituberculosis Immunotherapy

“…NAC at high doses was also found to act as a pro-oxidant, as it could decrease the GSH levels and increase the GSSG levels in healthy human subjects (50). It will be pertinent to mention in this paper that NAC can also act as prooxidant in the presence of certain compounds like vitamin B12b (51). Nevertheless, NAC can act as pro-oxidant or antioxidant depending on the pre-existing redox state.…”

Dual behavior ofN-acetylcysteine during ethanol-induced oxidative stress in embryonic chick brains

“…52 Low to moderate exogenous NAC concentrations can form NAC sulfhydryl ions; scavenge electrons onto exposed ionized sulfhydryl groups; and create NAC thiyl radicals (NAC −· ). 24 Without additional free NAC ions (NAC − ), as possibly seen in medium NAC-treated embryos, NAC thiyl radicals (NAC −· ) may perpetuate peroxidation; create HO −· ; cleave long-chain PUFAs into shorter less saturated fatty acids; and deplete GSH through the formation of GSH-adducts. 9 Recently, NAC pretreatments attenuated EtOH-induced liver damage in mice, but NAC post-treatments acted as prooxidants and aggravated EtOH-induced liver damage.…”

“…By binding Cu 2+ and/or Fe 3+ ions, glutathiyl radicals (GS −· ) and NAC thiyl radicals (NAC −· ) are formed and may transfer electrons to HO − ions or O 2 creating hydroxyl radicals (HO −· ) or oxygen radicals (O −· 2 ). 24 The exact point where an antioxidant becomes a prooxidant can be altered by intracellular concentrations of other antioxidants and the relative lack of GPx (EC 1.11.1.9) and other GSH-dependent enzymes favor high GSH levels at 10-13 days of chick development (stages [36][37][38][39] and may favor reactive oxygen species synthesis via NAC thiyl radicals as compared to GSH thyil radicals. 15,25 Whether NAC is a prooxidant or an antioxidant may be dose-dependent.…”