Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0920646 (renal ischemia)
 2,515 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of 5-lipoxygenase (5-LOX) in the pathophysiology of renal ischemia/reperfusion (I/R) injury is not known. Here we investigate the effects of 1) the 5-LOX inhibitor zileuton and 2) 5-LOX gene knockout (5-LOX(-/-)) mice on renal dysfunction and injury caused by I/R of the kidney in mice. Wild-type mice treated with zileuton (3 mg/kg i.v.) or 5-LOX(-/-) mice were subjected to bilateral renal artery occlusion (30 min) followed by reperfusion (24 h). Plasma urea, creatinine, and aspartate aminotransferase (AST) were measured as markers of renal dysfunction and reperfusion injury. Kidneys were used for histological evaluation of renal injury. Renal myeloperoxidase activity was measured and used as an indicator of polymorphonuclear leukocyte (PMN) infiltration and renal expression of intercellular adhesion molecule-1 (ICAM-1) was determined using immunohistochemistry. Administration of zileuton before I/R significantly reduced the degree of renal dysfunction (urea, creatinine) and injury (AST, histology). In addition, zileuton reduced the expression of ICAM-1 and the associated PMN infiltration caused by I/R of the mouse kidney. Compared with wild-type mice, the degree of renal dysfunction, injury, and inflammation caused by I/R in 5-LOX(-/-) mice was also significantly reduced, confirming the pathophysiological role of 5-LOX in the development of renal I/R injury. We propose that 1) endogenous 5-LOX metabolites enhance the degree of renal injury, dysfunction, and inflammation caused by I/R of the kidney by promoting the expression of adhesion molecules, and 2) inhibitors of 5-LOX may be useful in the treatment of conditions associated with I/R of the kidney.
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PMID:Reduction of renal ischemia-reperfusion injury in 5-lipoxygenase knockout mice and by the 5-lipoxygenase inhibitor zileuton. 1526 12

Renal ischaemia-reperfusion (I/R) injury is a clinically significant problem and an invariable consequence of renal transplantation. The problem begins at the onset of acute tubular necrosis (ATN), when the transplantation takes a long ischaemic interval by using the cardiac arrest donor's kidney. In addition, the longer the ischaemic interval, the higher the incidence rate of ATN. It is clinically important that renal I/R injury is reduced. The antisense oligodeoxynucleotide (AS-ODN), developed as a therapy for intractable diseases at the gene level, has recently been established as an important method in examining specific gene functions. The authors have previously demonstrated that AS-ODN/tissue factor (TF) prevents renal I/R injury. This review discusses the efficacy of AS-ODN/TF and AS-ODN/intercellular adhesion molecule-1 as existing targets, and the potential of AS-ODN/nuclear factor-kappaB, AS-ODN/cyclooxygenase and AS-ODN/5-lipoxygenase as prospective targets.
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PMID:Prospects of antisense oligodeoxynucleotides to alleviate renal ischaemia-reperfusion injury. 1557 55