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SAGE KE Bulletin Board

Eukarion antioxidant efficacy in Flies

11 June 2002

Simon Melov

Dear Matt, as I mentioned in my original posting, the compounds can break down into toxic by-products, and potentially it could be these break down products which are causing the toxicity. With regard to your second question, the results of the studies on wild-type mice are on-going and will be reported in the literature when they are completed (either positive or negative results). Such studies are labor intensive and by definition long. Mice are not flies or worms! Your third question is a good one, and we are addressing this in current studies. I know that the Lithgow lab is also carrying out studies in this area. I'm not sure what you mean by the E.coli question. Perhaps you are suggesting that ROS produced by E.coli in liquid media is a significant factor in limiting lifespan in worms? If so, this doesnt agree with survival data on plates, where the concentration of bacteria is far higher, but survival is essentially the same. Ultimately, pharmacokinetic questions are best addressed in rodents, as these studies are very difficult to do in invertebrates. One could imagine that having established that compounds get into the worm (possibly through the cuticle), which tissue is responding best to the drugs? perhaps it is muscle? perhaps it is the nervous system? I for one, do not want to be dissecting out 302 neurons to carry out analysis which would let me know the comparitive rates of uptake compared to other tissues. As a model system, C.elegans has its strengths and weaknesses, pharmacokinetics and biochemistry are not its strong points.


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