BACKGROUND: The pathophysiologic and potential therapeutic role of selectins in @entity8 ( @entity5721 ) is not fully understood, due in part to redundancy in the roles of individual selectins. We hypothesized that blockade of ligands for all three selectins using a novel small molecule ( @entity22423 ) would improve the course of renal @entity5721 by overcoming redundancy issues. This was investigated in a @entity35 model of renal @entity5721 . METHODS: @entity35 were treated with @entity22423 either during or post- @entity5721 . The effects of @entity22423 were investigated in two models of renal @entity5721 : moderate @entity5721 (30 minutes bilateral renal artery clamping) and severe @entity5721 (45 minutes clamping). The combination of anti-E- and anti-P-selectin antibodies also was investigated in @entity35 subjected to moderate @entity5721 . Renal function, histological injury and mortality were assessed. RESULTS: @entity35 treated with @entity22423 during moderate @entity5721 showed significantly reduced serum @entity1011 (SCr) and @entity4295 post- @entity63 compared to control animals. By contrast, delayed treatment (post- @entity5721 ) did not show a reduction in SCr. In @entity35 with severe @entity5721 , @entity22423 treatment during @entity5721 significantly reduced mortality at 48 hours post- @entity63 . @entity35 with moderate @entity5721 and treated with the combination of anti-E- and anti-P-selectin antibodies showed significantly reduced SCr compared to control @entity35 at 24 hours post- @entity63 . CONCLUSIONS: Small molecule selectin ligand inhibition provides a novel and effective approach to attenuate ischemic @entity810 . Timing of treatment is crucial to success.

Small molecule selectin ligand inhibition improves outcome in ischemic XXXX .

@entity8 :: ('MESH:D007674', 'Disease') :: ['renal ischemia-reperfusion injury'] @entity5721 :: ('MESH:D015427', 'Disease') :: ['IRI'] @entity4295 :: ('MESH:D007683', 'Disease') :: ['tubular necrosis'] @entity63 :: ('MESH:D007511', 'Disease') :: ['ischemia'] @entity22423 :: ('MESH:C108700', 'Chemical') :: ['TBC-1269'] @entity810 :: ('MESH:D058186', 'Disease') :: ['acute renal failure'] @entity1011 :: ('MESH:D003404', 'Chemical') :: ['creatinine'] @entity35 :: ('10116', 'Species') :: ['rat', 'Rats', 'rats']
@entity810 :: (MESH:D058186,Disease) :: ['acute renal failure']
