http://www.sciencedirect.com/science/article/pii/S1357272598000156
http://online.liebertpub.com/doi/abs/10.1089/ars.2005.7.32
I think that metabolite model of MDMA neurotoxicity theorizes that oxidative stress causes the damage indirectly by inducing glutathione activity. Certainly, something more than oxidative stress is needed to explain what's going on, since alpha-methyldopamine, itself an oxidant, can be injected directly into a rat brain in concentrations sufficient to release and deplete 75% of dopamine, but not cause any long-term depletion.
Still, it's entirely possible that glutathione or metabolites have nothing to do with DAergic toxicity.
Edit: Except apparently glutathione is still protective against MDMA neurotoxicity?
http://www.sciencedirect.com/science/article/pii/S0028390802004112
I'm confused.
Well I did some reading and here's my take on this issue:
-Oxidative stress is one of or the primary mediators of cell damage in MDMA and (Meth)AMP
-Glutathione conjugation up to a point where the body can not remove the resulting conjugates from circulation is good, as it reduces oxidative stress.
-Excess glutatione conjugates act in a unique fashion to cause apoptosis, perhaps recognition by death receptors/ increased uptake/ novel binding affinities?
-While your study is on epithelial cells in the lung, there is the distinct possibility that this may happen in vivo but there is no way in hell I'm paying $59.00 to check the concentrations they used in that study.
-The rat liver study showed only a 1.4x increase in GST, granted its a very small measure of a complex system. My thoughts are that there is only mild effects at relevant human dosage.
But keep up the good work man, ain't no review but peer review =)
But as for a brief summery of what I saw for the antioxidant stuff:
-NAC is
really bad long term
-PQQ is too novel to really give a solid review, but has the potential to be stunning so far.
-Selenium is actually required for proper antioxidant defenses, but for the love of god don't megadose it.
-Melatonin is safe up to a gram a day from a few studies I found, no real info on it downregulating anything at reasonable doses.