Journal Article

Renoprotective potency of amifostine in rat renal ischaemia–reperfusion

Mohammed Koussai Chok, Marc Conti, Abdelhamid Almolki, Sophie Ferlicot, Sylvain Loric, Antoine Dürrbach, Gérard Benoît, Stéphane Droupy and Pascal Eschwège

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 25, issue 12, pages 3845-3851
Published in print December 2010 | ISSN: 0931-0509
Published online June 2010 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfq314
Renoprotective potency of amifostine in rat renal ischaemia–reperfusion

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Purpose. Kidneys from haemodynamically unstable donors may suffer from renal ischaemia–reperfusion (RIR) injury. RIR is associated with reactive oxygen species production that induces inflammation and activates the arachidonic acid (AA) pathway which converts AA into prostaglandin E2. Amifostine was investigated for its renoprotective potential in RIR.

Materials and methods. The effect of amifostine (25 mg/kg  =  910 mg/m2) on the COX pathway, enzymatic antioxidant activity, the lipid peroxidation marker MDA, serum creatinine and apoptosis was determined in rats. Kidneys were subjected to 45 min of ischaemia and 1 or 24 h of reperfusion. Control groups (sham: coeliotomy, no ischaemia; r1: 45 min ischaemia/1 h reperfusion; r2: 45 min ischaemia/24 h reperfusion) were administered physiological saline intraperitoneally, and treated groups (E1: 45 min ischaemia/1 h reperfusion; E2: 45 min ischaemia/24 h reperfusion) received amifostine 30 min before reperfusion.

Results. Serum creatinine increased in non-treated control rats: r1 vs sham (1.6-fold; P <0.007), r2 vs sham (2-fold; P <0.007). Amifostine decreased serum creatinine levels in treated rats: E1 vs r1 (8%; P <0.0025), E2 vs r2 (44%; P <0.0025). Amifostine reduced acute tubular necrosis (25%) 24 h after reperfusion: E1 vs r1 (P <0.004), E2 vs r2 (P <0.03) and reduced COX-2 and microsomal prostaglandin E synthase expression: E1 vs r1 (P <0.03), E2 vs r2 (P <0.02). Amifostine decreased MDA (P <0.04) and reduced caspase-3 expression but did not alter enzymatic antioxidant activity after RIR.

Conclusions. Amifostine decreased the degree and severity of tubular damage after reperfusion, probably by scavenging oxygen free radicals and attenuating the cytotoxic effects of inflammatory infiltrates and apoptosis.

Keywords: amifostine; cyclooxygenase; ischaemia–reperfusion; kidney; reactive oxygen species

Journal Article.  5086 words.  Illustrated.

Subjects: Nephrology

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