STOBADINE PROTECTS RAT KIDNEY AGAINST ISCHAEMIA/REPERFUSION INJURY

SUMMARY 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.