Adenine metabolite pool especially ATP concentration is a reliable
index of cellular energy state of viable tissues. In this work both adenine
metabolite pool of canine pancreas and ATPase activity of isolated
mitochondria and microsomes in basal state and during normothermic
ischemia were detected. This may give information about its susceptibility
to tissue ischemia . It may occur during the time elapsed between its
separation and transplantation. Moreover the effect of cytoprotective agent
nitrobenzyl thioinosine on above mentioned parameters was determined.
The study revealed that pancreas is more vulnerable to the metabolic
sequelae of tissue ischemia due to low basal level of ATP and high ATPase
activity . Normothermic ischemia depleted ATP, ADP and adenosine
contents after 20 minutes . Precursors of free radicals namely inosine level
was significantly increased. NBMPR improved the tolerability of isolated
pancreas to tissue ischemia. It delayed the ischemic mediated depletion of
ATP by inhibiting its of breakdown by mitochondrial and microsomal ATP
ases and activation of its salvage through increasing the availability of its
precursor (adenosine). Moreover de-novo ATP synthesis may be enhanced by
stimulation of glycolysis . This may rationalize the use of the tested drug
during islet cell or whole pancreatic transplantation. Its in-vivo use to prolong
islet cell survival after transplantation needs detailed study on its effect on
carbohydrate metabolism in diabetic patients. |
