Ischemic injury to the kidney is characterized in part by
nucleotide depletion and tubular cell death in the form of
necrosis or apoptosis. Recently, we linked
anoxia-induced apoptosis in renal cell cultures specifically to the depletion of
GTP. We therefore hypothesized that enhancing
GTP repletion in vivo might protect function by reducing apoptosis in postischemic tubules. Male C57 black mice (the "I" group of animals) underwent bilateral renal artery clamp for 32 minutes to induce
ischemia and then received either
normal saline ("NS") or
guanosine ("G"). After 1 hour of reperfusion, renal
GTP levels in NS/I were reduced to nearly half of those in
sham operated mice, whereas these levels were nearly unchanged in G/I mice. Morphologic examination of tubular injury revealed no significant differences between the two groups. However, there was a significant reduction in the number of apoptotic tubular cells in the medulla in the G/I group as compared with the NS/I group. At 24 hours,
creatinine was significantly elevated in the NS/I group, compared to the G/I group. We conclude that
guanosine protects against renal ischemic injury by replenishing
GTP stores and preventing tubular apoptosis.