The beneficial effect of 2'-deoxycoformycin in renal ischemia-reperfusion is mediated both by preservation of tissue ATP and inhibition of lipid peroxidation.
Renal ischemia injures the renal tubular cell by disrupting the vital cellular metabolic machinery. Further cell damage is caused when the blood flow is restored by oxygen free radicals that are generated from xanthine oxidase. Oxygen radicals cause lipid peroxidation of cell and organelle membranes, disrupting the structural integrity and capacity for cell transport and energy metabolism. In the present study, the possible therapeutic usefulness of the adenosine deaminase inhibitor, 2'-deoxycoformycin (DCF), during renal ischemia and reperfusion injury was investigated. The effects of DCF on renal malondialdehyde (MDA) and ATP levels were studied after 45 min ischemia and 15 min subsequent reperfusion in rat kidneys. MDA levels remained unchanged during ischemia, but increased after the subsequent reperfusion. DCF pretreatment (2.0 mg/kg i.m.) decreased MDA and increased ATP levels during the ischemia-reperfusion period. DCF exerts a dual protective action by facilitating purine salvage for ATP synthesis and inhibiting oxygen radical-induced lipid peroxidation. These results suggest that DCF therapy could be beneficial in the treatment of ischemia-reperfusion renal injuries.
Bor
M V
MV
Department of Clinical Biochemistry, Gazi University School of Medicine, Ankara, Turkey.
Durmuş
O
O
Bilgihan
A
A
Cevik
C
C
Türközkan
N
N
D000241:Adenosine / Q000378:metabolism; D058892:Adenosine Deaminase Inhibitors; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D007511:Ischemia / Q000188:drug therapy*; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects / Q000201:enzymology; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress; D015649:Pentostatin / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species; D015427:Reperfusion Injury / Q000188:drug therapy*; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D014969:Xanthine Oxidase / Q000378:metabolism
D058892:Adenosine Deaminase Inhibitors; D000975:Antioxidants; D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D015649:Pentostatin; D008315:Malondialdehyde; D000255:Adenosine Triphosphate; D014969:Xanthine Oxidase; D000241:Adenosine