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Guanosine supplementation reduces apoptosis and protects renal function in the setting of ischemic injury
K.J. Kelly, … , Zoya Plotkin, Pierre C. Dagher
K.J. Kelly, … , Zoya Plotkin, Pierre C. Dagher
Published November 1, 2001
Citation Information: J Clin Invest. 2001;108(9):1291-1298. https://doi.org/10.1172/JCI13018.
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Article

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.

Authors

K.J. Kelly, Zoya Plotkin, Pierre C. Dagher

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Figure 9

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Effects of guanosine on nucleotide levels and apoptosis after chemical a...
Effects of guanosine on nucleotide levels and apoptosis after chemical anoxia recovery in LLC-PK1 cells. Values are means ± SE. (a) LLC-PK1 cells were treated for 45 minutes with 0.1 μM antimycin A in depleted media followed by recovery for 2 hours. Nucleotides were measured at 45 minutes of depletion (n = 7) and at 2 hours of recovery (n = 6). (b) Cells were treated identically except for the addition of 200 μM guanosine to the recovery medium (n = 6). (c and d) Representative fields of confocal microscopic images of LLC-PK1 cells at 24 hours after recovery from chemical anoxia. Cells were costained with Hoechst 33342 and propidium iodide as detailed in Methods. In c, cells recovered in regular media. Apoptotic features such as condensation and fragmentation of chromatin is seen in most cells in the field. In d, cells recovered in the presence of 200 μM guanosine. Most nuclei showed normal morphology, and only few had apoptotic features.

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