Ethanol-Induced Lipid Peroxidation and Apoptosis in Embryopathy

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

“…[5][6][7][8][9][10]19 Yet, NAC treatments in U-strain rat embryos diminished but failed to completely normalize EtOH-increased Bax/ Bcl-2 ratios. 19 Bax is a pro-apoptotic protein and Bcl-2 is an anti-apoptotic protein.…”

“…[5][6][7][8][9][10][11][12][13][14] EtOH treatments during early chick embryogenesis caused decreased brain membrane long-chain polyunsaturated fatty acids (PUFA) levels, decreased brain glutathione (GSH) levels, increased brain homocysteine levels, increased brain lipid hydroperoxide (LPO) levels, and reduced embryo viability as measured by EtOH-induced decreased brain masses and increased brain caspase-3 activities in theoretical stage 37 chick embryos. 9,[11][12][13][14][15] Early embryonic EtOH exposure caused reduced neuron densities within the cerebral hemisphere that correlated with EtOH-induced reductions in brain unsaturated/saturated membrane fatty acid ratios with a correlation coefficient (r) of 0.52 (P < 0.0002) in stage 44 chick embryos. 16 Exogenous α-tocopherol and γ-tocopherol, known antioxidants, attenuated EtOH-reduced brain membrane long-chain PUFA levels and EtOH-induced increased brain LPO levels in stage 44 embryos.…”

“…19 Bax is a pro-apoptotic protein and Bcl-2 is an anti-apoptotic protein. 9 NAC (N-acetyl-L-cysteine) enters cells and is deacetylated into L-cysteine. Increased L-cysteine levels, along with glutamate and glycine, serve as substrates in replenishing GSH levels.…”

“…20,21 Because GSH is a substrate for glutathione peroxidases (GPx) (EC 1.11.1.9 and EC 1.11.1.12), which catalyze the reduction of H 2 O 2 and LPOs to water and corresponding alcohols, NAC and/or GSH supplementation have been used during oxidative stress. 5,[7][8][9]19,[21][22][23] While NAC and GSH are known antioxidants, NAC and GSH can become prooxidants. 5,[7][8][9]19,21,22 This may be surprising until one remembers that antioxidants, such as GSH and NAC, become prooxidants after scavenging electrons from reactive species, including hydroxyl radicals (HO −· ), peroxynitrite radicals, and carbon-centered radicals including LPOs.…”

“…5,[7][8][9]19,[21][22][23] While NAC and GSH are known antioxidants, NAC and GSH can become prooxidants. 5,[7][8][9]19,21,22 This may be surprising until one remembers that antioxidants, such as GSH and NAC, become prooxidants after scavenging electrons from reactive species, including hydroxyl radicals (HO −· ), peroxynitrite radicals, and carbon-centered radicals including LPOs. Electron scavenging within GSH and NAC is done at ionized sulfhydryl groups causing GSH − ions to become glutathiyl radicals (GS −· ) and NAC − ions to become NAC thiyl radicals (NAC −· ).…”