Effect of bioflavonoids quercetin and curcumin on ischemic renal injury: a new class of renoprotective agents.
BACKGROUND
Nonimmune renal injury plays an important role in acute and chronic rejection by triggering an injury response through cytokine and chemokine release. Bioflavonoids are agents with potential immunosuppressive and renoprotective properties. We studied the effects of quercetin and curcumin, two bioflavonoids, on ischemia-reperfusion in the rat.


METHODS
Rats underwent 30 min of left renal pedicle occlusion with simultaneous right nephrectomy and were pretreated with quercetin or curcumin. Serial serum creatinine was measured, and renal expression of the chemokines regulated upon activation, normal T-cell expressed and secreted (RANTES), monocyte chemoattractant protein-1 (MCP-1), and allograft inflammatory factor (AIF) was quantified by polymerase chain reaction.


RESULTS
Pretreatment with quercetin or curcumin resulted in preservation of histological integrity, with a decrease in tubular damage and interstitial inflammation. On day 2 after ischemia-reperfusion, quercetin pretreatment decreased the mean serum creatinine level from 6.5+/-1.4 to 3.3+/-0.5 mg/dl (P=0.06). On day 7, the creatinine level for control animals was 7.5+/-1.5 mg/dl, which was significantly decreased by pretreatment with quercetin, curcumin, or both together (creatinine levels: 1.6+/-1.3, 1.8+/-0.2, and 2.0+/-0.4 mg/dl, respectively; all P<0.05 vs. untreated). By semiquantitative polymerase chain reaction, RANTES, MCP-1, and AIF were detected at high levels in kidneys on day 2 but not in normal kidneys. Pretreatment with quercetin or curcumin strongly attenuated this expression.


CONCLUSIONS
Quercetin and curcumin reduce ischemia-reperfusion injury and its inflammatory sequelae. The bioflavonoids hold promise as agents that can reduce immune and nonimmune renal injury, the key risk factors in chronic graft loss.
Department of Surgery, Harbor-UCLA Medical Center, UCLA School of Medicine, Torrance, California 90509, USA. dshoskes@ucla.edu
D A
DA
Shoskes
D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics; D018946:Chemokine CCL5 / Q000235:genetics; D003474:Curcumin / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D007511:Ischemia / Q000188:drug therapy* / Q000378:metabolism; D007668:Kidney / Q000098:blood supply*; D008297:Male; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D015427:Reperfusion Injury / Q000517:prevention & control*
D018932:Chemokine CCL2; D018946:Chemokine CCL5; D011794:Quercetin; D003474:Curcumin