X-Message-Number: 12939
Date: Tue, 14 Dec 1999 07:49:23 -0800 (PST)
From: Doug Skrecky <>
Subject: 25'th update on fly longevity experiments

   This is the 25'th update on my fly longevity experiments. Runs #19 and
 #20 investigated ways and means for blocking short-term glycerol induced
 "metabolic" toxicity. In place of the water normally used in these
 experiments, a 1:2 mixture of glycerin (glycerol) and water is used. This
 is quite dehydrating, so I expected the flies to die of dehydration after
 a short period, which is what happened.
   In run #19 good results were obtained by a grape proanthocyanidin
 mixture called leucoselect. The glycerol induced increase in mortality
 evident at the census on Day 5, 9, and 12 was completely reversed by
 leucoselect, so that survival rates were similar to a control bottle
 which used water in place of the glycerol mixture.
   Please note that all bottles included taurine, as a non-toxic
 larvicide, so as to avoid having to regularly change the fly food.
 Benzoate, and citric acid were also included to help eliminate pathogen
 growth on the 4-24 fly food, which itself already includes a not
 completely effective mold inhibitor.

 RUN #19                      Percent Survival on Day
                       5   9  12  17  20  25  32  37  43 55 60
 ______________________________________________________________
 water cntl           97% 91% 77% 66% 54% 49% 37% 31% 14% 6% 3%
 glycerol 1:2 cntl    62  29  10   0   -   -   -   -   -  -  -
  +aloe vera 450 mg   81  52  43   5   0   -   -   -   -  -  -
  +lavendar 300 mg    73  40  20   0   -   -   -   -   -  -  -
  +leucoselect 50 mg  91  87  83  30   4   0   -   -   -  -  -
  +oleuropein 50 mg   57  20   5   0   -   -   -   -   -  -  -

   I was so impressed with the results with leucoselect that the glycerol
 experiment was immediately repeated. I also tested the effect of a higher
 dosage of leucoselect, as well as some related chemicals. For some reason
 the day 12 results were not quite as good, possibly because the flies
 used were a little older to start with in this run. However the higher
 100 mg dosage of Leucoselect offered survival rates not significantly
 different from the water control on the day 4, and day 7 census.

 RUN #20                      Percent Survival on Day
                            4   7  12  19  26  30
 __________________________________________________________________
 water cntl               100% 86% 79% 50% 21%  7%
 glycerol 1:2 cntl         91  27   9   0   -   -
  +leucoselect 50 mg       87  67  40   0   -   -
  +leucoselect 100 mg     100  82  27   0   -   -
  +resveratrol 50 mg       95  70  40   0   -   -
  +pycnogenol 50 mg        93  60  33   0   -   -
  +green tea extract 75 mg 95  70  35   0   -   -

   It looks like a sufficiently high dosage of the grape extract
 leucoselect can eliminate glycerol induced increases in mortality rates,
 at least in the short term. I suspect quite a few other antioxidant
 mixtures would have similar effects if a high enough dosage were to be
 used.
   The metabolic toxicity of glycerol investigated here may have little to
 do with the toxic effects induced by the concentrated glycerol solutions
 used in cryopreservation. These are administered at a lower temperature,
 where metabolism is greatly reduced, so leucoselect might or might not
 have any beneficial effect in this case.
   In cryopreservation the major toxic effect of glycerol is known to be
 osmotic, since glycerol only slowly passes through cellular membranes.
 This feature renders glycerol of limited use for whole organ
 cryopreservation, which requires cryoprotectants possessing much greater
 permeability, so that organs can be protected from freezing injury in an
 acceptible time frame.
   Next I'll try to block the metabolic toxicity of alcohol.

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