Renoprotective potency of heme oxygenase-1 induction in rat renal ischemia-reperfusion.
| Autor: | Chok MK; Laboratoire de Chirurgie Expérimentale, UPRES EA 1602, Université Paris-Sud 11, Faculté de Médecine, Le Kremlin Bicêtre, France. peschwege@yahoo.com, Ferlicot S, Conti M, Almolki A, Dürrbach A, Loric S, Benoît G, Droupy S, Eschwège P |
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| Jazyk: | angličtina |
| Zdroj: | Inflammation & allergy drug targets [Inflamm Allergy Drug Targets] 2009 Sep; Vol. 8 (4), pp. 252-9. |
| DOI: | 10.2174/187152809789352186 |
| Abstrakt: | Purpose: Renal injury caused by ischemia-reperfusion (IR) can lead to acute renal failure or delayed graft function. Renal ischemia-reperfusion (RIR) induces inflammatory disorders via activation of arachidonic acid metabolism into prostaglandin E(2) (PGE(2)). Two inducible enzymes, COX-2 and microsomal prostaglandin E synthase (mPGES), regulate PGE(2) production. Heme oxygenase-1 (HO-1) is a cytoprotective enzyme activated during cellular stress. Overexpression of HO-1 is beneficial in transplantation models including antigen-independent IR injury, acute and chronic allograft rejection. Materials and Methods: We investigated the effect of HO-1 induction on the COX pathway, antioxidant enzyme activities, malondialdehyde (MDA) levels, and apoptosis in rat kidneys subjected to 45 min ischemia and 1 h or 24 h reperfusion. Rats were injected intraperitoneally with either: 50 mg/kg hemin (HO-1 inducer groups: H1, H2); 50 micromol/kg ZnPP (HO-1 inhibitor groups: Hz1, Hz2); or 0.9% saline (control groups: r1, r2). Sham animals (Sh) did not undergo RIR. Results: Serum creatinine increased significantly after RIR (r vs Sh; p <0.05). Hemin treatment induced a significant decrease in serum creatinine after RIR (H vs r; p <0.05) whereas ZnPP treatment significantly increased serum creatinine levels (Sh vs Hz; p <0.05). Hemin reduced the severity of acute tubular necrosis and significantly reduced COX-2 and mPGES expression (p <0.05). Hemin did not alter depleted antioxidant enzyme activity but did decrease levels of MDA (p <0.05). Hemin also reduced caspase-3 expression. Conclusions: HO-1 decreased the degree and severity of tubular damage after IR, probably by attenuating the cytotoxic effects of inflammatory infiltrates and apoptosis. |
| Databáze: | MEDLINE |
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