 |
 |
The abstract below from the Beilinson Medical Centre, Israel mentions N-acetyl-cysteine (NAC) as markedly protective of nigral cells and "highly effective in in rescuing cells from DA induced apoptosis" (better than vitamins C & E). NAC is available by mail order in the US but does anyone know of a UK supplier? John Meagher <[log in to unmask]> Abstract: Prevention of dopamine induced cell death by thiol antioxidants: possible Implications for treatment of Parkinson's disease. Offen D; Ziv I; Sternin H; Melamed E; Hochman A. Department of Neurology, Beilinson Medical Center, Petah-Tiqva, Israel. Exp Neurol Sep 1996 141(1) p32-9 "We have recently shown that dopamine (DA) can trigger apoptosis, an active program of cellular self~destruction, in various neuronal cultures and proposed that inappropriate activation of apoptosis by DA and or its oxidation products may initiate nigral cell loss in Parkinson's disease (PD). Since DA toxicity may be mediated via generation of oxygen-free radical species, we examined whether DA-induced cell death in PC 12 cells may be inhibited by antioxidants. We have found that the thiol containing compounds, reduced glutathione (GSH), N-acetyl-cysteine (NAC), and dithiothreitol (DTr) were markedly protective, while vitamins C and E had lesser or no effect. The thiol antioxidants and vitamin C but not vitamin E, prevented dopamine autooxidation and production of dopamine-melanin. Their protective effect has also manifested by inhibiting DA- induced apoptosis; DNA fragmentation was prevented as was shown histochemically by the in situ end-labeled DNA technique (TUNEL). Intracellular GSH and other thiols constitute an important nataral defense against oxidative stress. We have found that depletion of cellular GSH by the addition of phoron, a substrate of glutathione transferase, and buthionine suufoximine (BSO), an inhibitor of gamma-glutamyl transpeptidase, significantly enhanced DA toxicity. Cotreatment with NAC rescued the cells from the toxic effect of BSO+DA, and phoron+ DA, while addition of GSH provided only partial protection from BSO+DA toxicity. Our data indicate that the thiol fimily of antioxidants, but not vitamins C and E, are highly effective in rescuing cells from DA- induced apoptosis. Further study of the mechanisms underlying the unique protective capacity of thiol antioxidants may lead to the development of new neuroprotective theraputic strategies for PD."