Stobadine protects rat kidney against ischaemia/reperfusion injury


Guz G., Demirogullari B., Ulusu N. N., Dogu C., Demirtola A., Kavutcu M., ...Daha Fazla

Clinical and Experimental Pharmacology and Physiology, cilt.34, sa.3, ss.210-216, 2007 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 34 Sayı: 3
  • Basım Tarihi: 2007
  • Doi Numarası: 10.1111/j.1440-1681.2007.04574.x
  • Dergi Adı: Clinical and Experimental Pharmacology and Physiology
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.210-216
  • Anahtar Kelimeler: glutathione, ischaemia, kidney, malondialdehyde, reperfusion, stobadine, INDUCED DIABETIC-RATS, REPERFUSION-INDUCED INJURY, PENTOSE-PHOSPHATE PATHWAY, ACUTE-RENAL-FAILURE, LIPID-PEROXIDATION, VITAMIN-E, IN-VIVO, ANTIOXIDANT, GLUTATHIONE, ISCHEMIA
  • Gazi Üniversitesi Adresli: Evet

Özet

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. Iscahemia-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. © 2007 The Authors.