Guanosine supplementation reduces apoptosis and protects renal function inthe setting of ischemic injury

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