N-ACETYL-L-CYSTEINE IS A PLURIPOTENT PROTECTOR AGAINST CELL-DEATH AND ENHANCER OF TROPHIC FACTOR-MEDIATED CELL-SURVIVAL IN-VITRO

We have discovered that N-acetyl-L-cysteine (NAC) protects cells against death induced by exposure to noxious stimuli and against programed cell death (apoptosis) associated with exposure to inadequate amounts of trophic factors. NAC prevented glutamate-induced death of oligodendrocytes and tumor necrosis factor alpha (TNF-alpha)-induced death of oligodendrocytes and L929 fibroblasts. Moreover, suboptimal doses of NAC plus ciliary neurotrophic factor (which also protects oligodendrocytes against TNF-alpha-mediated killing) acted synergistically to protect oligodendrocytes against TNF-alpha-induced death. Protection against death by growth factor deprivation was provided by the combination of (i) NAC, vitamin C, or Trolox (a water-soluble analogue of vitamin E) with suboptimal concentrations of protein trophic factors, (ii) NAC, vitamin C, or Trolox with progesterone, and (iii) NAC with either vitamin C or Trolox; these latter experiments suggest that the addition of tyrosine kinase stimulators is not required to promote cell survival. In all paradigms, NAC was either equally or more effective than the other compounds examined. In light of the long history of therapeutic application of NAC, we suggest that use of this compound may be of interest in conditions where certain toxin-mediated forms of cell death and/or apoptosis contribute significantly to disease.