Tezosentan Reduces the Renal Injury Induced by Abdominal Aortic Ischemia-Reperfusion in Rats1

Gulmen, Senol; Kiris, Ilker; Narin, Cuneyt; Ceylan, Berit Gokce; Mermi, Betul; Sutcu, Recep; Meteoglu, Ibrahim

doi:10.1016/j.jss.2008.08.011

« Previous Next »Journal of Surgical Research
Volume 157, Issue 1 , Pages e7-e13, November 2009

Tezosentan Reduces the Renal Injury Induced by Abdominal Aortic Ischemia-Reperfusion in Rats¹

Senol Gulmen, M.D.
- Department of Cardiovascular Surgery, Suleyman Demirel University Medical School, Isparta, Turkey
- To whom correspondence and reprint requests should be addressed at Department of Cardiovascular Surgery, Suleyman Demirel University Medical School, Bahcelievler Mh Istanbul Cd Daloglu Apt No:59/1 Kat:4 Daire:14, 32200, Isparta, Turkey.
Ilker Kiris, M.D.
- Department of Cardiovascular Surgery, Suleyman Demirel University Medical School, Isparta, Turkey
Cuneyt Narin, M.D.
- Department of Cardiovascular Surgery, Selcuk University Meram Medical School, Konya, Turkey
Berit Gokce Ceylan, M.D.
- Department of Anesthesiology and Reanimation, Suleyman Demirel University Medical School, Isparta, Turkey
Betul Mermi, M.D.
- Department of Biochemistry, Suleyman Demirel University Medical School, Isparta, Turkey
Recep Sutcu, M.D.
- Department of Biochemistry, Suleyman Demirel University Medical School, Isparta, Turkey
Ibrahim Meteoglu, M.D.
- Department of Pathology, Adnan Menderes University Medical School, Aydın, Turkey

Received 2 June 2008 published online 27 October 2008.

Background

Renal injury induced by aortic ischemia-reperfusion (IR) is an important factor in the development of postoperative acute renal failure following abdominal aortic surgery. Endothelin (ET) is involved in the development of renal injury induced by aortic IR and tezosentan (R0 61-0612) is a specific ET receptor antagonist. The aim of this study was to examine the effect of tezosentan on renal injury induced by abdominal aortic IR in rats.

Material and Methods

Twenty-four Wistar-Albino rats were randomized into three groups (eight per group). Control group underwent laparotomy and dissection of the infrarenal abdominal aorta (IAA) without occlusion. The aortic IR group underwent laparotomy and clamping of the IAA for 120 min followed by 120 min of reperfusion. Aortic IR + tezosentan group underwent same aortic IR periods, and received a bolus intravenous injection of 10 mg/kg tezosentan before ischemia plus continuous intravenous infusion of 1 mg/kg/h tezosentan during 120 min ischemia and 120 min reperfusion. At the end of the experiment, blood and kidney tissue specimens were obtained for biochemical analysis. Histological evaluation of the rat kidney tissues was also done.

Results

Biochemical analysis showed that aortic IR significantly increased (P < 0.05 versus control) while tezosentan significantly decreased (P < 0.05 versus aortic IR) the tissue levels of malondialdehyde, superoxide dismutase, catalase and myeloperoxidase. Histological analyses showed that aortic IR significantly increased (P < 0.05 versus control) while tezosentan significantly decreased (P < 0.05 versus aortic IR) focal glomerular necrosis, dilatation of Bowman's capsule, degeneration of tubular epithelium, necrosis in tubular epithelium and tubular dilatation in the renal tissue samples.

Conclusion

The results of this study indicate that tezosentan reduces renal injury induced by aortic IR in rats. We think that tezosentan exerted this beneficial effect via reducing oxidative stress and lipid peroxidation, inhibition of leukocyte infiltration into renal tissue and acting cytoprotective on renal tubular cells after aortic IR.

Key Words: tezosentan, renal injury, abdominal aorta, ischemia-reperfusion