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STOBADINE PROTECTS RAT KIDNEY AGAINST ISCHAEMIA/REPERFUSION INJURY
Author(s) -
Guz Galip,
Demirogullari Billur,
Ulusu Nuray N,
Dogu Cihangir,
Demirtola Arzu,
Kavutcu Mustafa,
Omeroglu Suna,
Stefek Milan,
Karasu Cimen
Publication year - 2007
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2007.04574.x
Subject(s) - glutathione peroxidase , malondialdehyde , kidney , medicine , creatinine , reperfusion injury , glutathione , blood urea nitrogen , endocrinology , pharmacology , oxidative stress , chemistry , superoxide dismutase , ischemia , biochemistry , enzyme
SUMMARY1 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.