The role of cycloxygenase-2 in the rodent kidney following ischaemia/reperfusion injury in vivo.
The role of cyclooxygenase-2 (COX-2) in the pathophysiology of renal ischaemia/reperfusion injury is still not fully understood. In order to elucidate the role of COX-2 in ischaemia/reperfusion injury of the kidney, we have evaluated the effects of ischaemia/reperfusion on renal dysfunction and injury in (i) rats treated with either vehicle or the selective COX-2 inhibitor parecoxib, and (ii) wild-type mice or mice in which the gene for COX-2 has been deleted (COX-2 knock-out mice or COX-2(-/-)). Rats were subjected to bilateral renal ischaemia (45 min) and reperfusion (6 h), and received parecoxib (20 mg/kg, i.v.) 30 min prior to ischaemia and 3 h after the commencement of reperfusion. Serum urea, serum creatinine, serum aspartate aminotransferase, creatinine clearance and fractional excretion of sodium were all used as indicators of renal dysfunction and injury. Mice (wild-type and COX-2(-/-)) were subjected to bilateral renal ischaemia (30 min) and reperfusion (24 h) after which renal dysfunction (serum urea and creatinine) and renal injury was assessed by histological analysis. Parecoxib significantly augmented the degree of renal dysfunction and injury caused by ischaemia/reperfusion in the rat. In addition, the degree of renal injury and dysfunction caused by ischaemia/reperfusion was also significantly augmented in COX-2(-/-) mice when compared to their wild-type littermates. These findings support the view that metabolites of COX-2 protect the kidney against ischaemia/reperfusion injury, and (ii) that selective inhibitors of COX-2 may worsen renal dysfunction and injury in conditions associated with renal ischaemia.
Patel
Nimesh S A
NS
Centre for Experimental Medicine and Nephrology and Critical Care, William Harvey Research Institute, St. Bartholomew's and The Royal London School of Medicine and Dentistry, Queen Mary - University of London, London, UK. n.s.patel@qmul.ac.uk
Cuzzocrea
Salvatore
S
Collino
Massimo
M
Chaterjee
Prabal K
PK
Mazzon
Emanuela
E
Britti
Domenico
D
Yaqoob
Muhammad M
MM
Thiemermann
Christoph
C
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D007275:Injections, Intravenous; D007555:Isoxazoles / Q000008:administration & dosage / Q000494:pharmacology*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology*; D007678:Kidney Glomerulus / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology; D007684:Kidney Tubules / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000503:physiopathology*; D013997:Time Factors
D016861:Cyclooxygenase Inhibitors; D007555:Isoxazoles; C409945:parecoxib; D051546:Cyclooxygenase 2