Stobadine protects rat kidney against ischaemia/reperfusion injury.
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.
Guz
Galip
G
Department of Nephrology, Gazi University Faculty of Medicine, Ankara, Turkey. galip_guz@hotmail.com
Demirogullari
Billur
B
Ulusu
Nuray N
NN
Dogu
Cihangir
C
Demirtola
Arzu
A
Kavutcu
Mustafa
M
Omeroglu
Suna
S
Stefek
Milan
M
Karasu
Cimen
C
D000818:Animals; D001806:Blood Urea Nitrogen; D002243:Carbolines / Q000627:therapeutic use*; D003404:Creatinine / Q000097:blood; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D007150:Immunohistochemistry; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D007674:Kidney Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D010427:Pentose Phosphate Pathway / Q000187:drug effects; D010734:Phosphogluconate Dehydrogenase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*
D002243:Carbolines; D008315:Malondialdehyde; D003404:Creatinine; D010734:Phosphogluconate Dehydrogenase; D005954:Glucosephosphate Dehydrogenase; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005978:Glutathione; C100106:dicarbine