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

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Abstract

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.

Original languageEnglish
Pages (from-to)1291-1298
Number of pages8
JournalJournal of Clinical Investigation
Volume108
Issue number9
DOIs
StatePublished - 2001

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Guanosine
Guanosine Triphosphate
Apoptosis
Kidney
Wounds and Injuries
Renal Artery
Reperfusion
Creatinine
Cell Death
Necrosis
Ischemia
Nucleotides
Cell Culture Techniques

ASJC Scopus subject areas

  • Medicine(all)

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Guanosine supplementation reduces apoptosis and protects renal function in the setting of ischemic injury. / Kelly, Katherine; Plotkin, Zoya; Dagher, Pierre.

In: Journal of Clinical Investigation, Vol. 108, No. 9, 2001, p. 1291-1298.

Research output: Contribution to journalArticle

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