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PMID:17250641

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Citation

Guz, G, Demirogullari, B, Ulusu, NN, Dogu, C, Demirtola, A, Kavutcu, M, Omeroglu, S, Stefek, M and Karasu, C (2007) Stobadine protects rat kidney against ischaemia/reperfusion injury. Clin. Exp. Pharmacol. Physiol. 34:210-6

Abstract

1. Ischaemia-reperfusion (I/R) injury, one of the main causes of acute renal failure, still needs satisfactory treatment for routine clinical application. Stobadine, a novel synthetic pyridoindole anti-oxidant, has the ability to reduce tissue injury induced by mechanisms involving reactive oxygen species during I/R. The aim of the present study was to determine the effects of stobadine on renal I/R injury. 2. Forty male Wistar rats were randomly divided into four groups as follows: sham, I/R, stobadine treated and I/R + stobadine treated. Stobadine (2 mg/kg, i.v.) was given intravenously to two groups of rats. The stobadine-treated group was treated with stobadine following sham operation before the abdominal wall was closed, whereas the I/R + stobadine group received stobadine at the beginning of reperfusion. Renal I/R was achieved by occluding the renal arteries bilaterally for 40 min, followed by 6 h reperfusion. Immediately thereafter, blood was drawn and tissue samples were harvested to assess: (i) serum levels of blood urea nitrogen and creatinine; (ii) serum and/or tissue levels of malondialdehyde (MDA), glutathione (GSH), glucose 6-phosphate dehydrogenase (G-6PD), 6-phosphogluconate dehydrogenase (6-PGD), glutathione reductase (GR) and glutathione peroxidase (GPx); (iii) renal morphology; and (iv) immunohistochemical staining for P-selectin. 3. Stobadine was able to significantly attenuate the renal dysfunction as a result of renal I/R injury. Ischaemia-reperfusion resulted in a significant increase in serum and kidney MDA levels and a decrease in serum and kidney GSH. Stobadine treatment at the beginning of reperfusion attenuated both the increased MDA levels and decreased GSH secondary to I/R injury. In addition, the decreased G-6PD activity observed after I/R was significantly attenuated by stobadine treatment. Stobadine did not alter 6-PGD activity after I/R. Neither GR nor GPx activity was significantly changed in the I/R alone or the I/R + stobadine groups compared with the sham group. In addition, stobadine decreased the morphological deterioration and high P-selectin immunoreactivity secondary to renal I/R injury. 4. A pyridoindole anti-oxidant, stobadine exerts a renal protective effect in renal I/R injury, which is probably due to its radical-scavenging and anti-oxidant activities.

Links

PubMed Online version:10.1111/j.1440-1681.2007.04574.x

Keywords

Animals; Blood Urea Nitrogen; Carbolines/therapeutic use; Creatinine/blood; Glucosephosphate Dehydrogenase/metabolism; Glutathione/metabolism; Glutathione Peroxidase/metabolism; Glutathione Reductase/metabolism; Immunohistochemistry; Injections, Intravenous; Kidney/drug effects; Kidney/enzymology; Kidney Diseases/etiology; Kidney Diseases/pathology; Kidney Diseases/prevention & control; Male; Malondialdehyde/metabolism; Pentose Phosphate Pathway/drug effects; Phosphogluconate Dehydrogenase/metabolism; Rats; Rats, Wistar; Reperfusion Injury/etiology; Reperfusion Injury/pathology; Reperfusion Injury/prevention & control

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:G6PD

involved_in

GO:0014070: response to organic cyclic compound

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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