Selective inhibition of cyclooxygenase 2 spares renal function and prostaglandin synthesis in cirrhotic rats with ascites.
OBJECTIVE
The critical role of cyclooxygenase (COX) products in maintenance of renal function in cirrhosis with ascites discourages the use of nonsteroidal anti-inflammatory drugs in this disease. The recent development of selective COX-2 inhibitors opens new avenues for the use of these compounds in decompensated cirrhosis. The current study evaluates the effects of a selective COX-2 inhibitor (SC-236) on renal function in cirrhotic rats with ascites.


METHODS
In protocol 1, urine volume, urinary excretion of sodium and prostaglandins, glomerular filtration rate, and renal plasma flow were measured before and after administration of SC-236 (n = 12) or ketorolac (n = 10) to rats with cirrhosis. Protocol 2 was aimed at assessing the effects of COX inhibitors on renal water metabolism in 28 cirrhotic rats.


RESULTS
Administration of SC-236 to cirrhotic animals did not produce significant renal effects, whereas administration of the nonselective COX-1/COX-2 inhibitor, ketorolac, resulted in a marked reduction in urine volume, urinary excretion of prostaglandins, and glomerular filtration rate and in a significant impairment in renal water metabolism.


CONCLUSIONS
These findings indicate that SC-236 does not significantly impair renal function in rats with cirrhosis.
Bosch-Marcè
M
M
DNA Unit, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.
Clària
J
J
Titos
E
E
Masferrer
J L
JL
Altuna
R
R
Poo
J L
JL
Jiménez
W
W
Arroyo
V
V
Rivera
F
F
Rodés
J
J
D000818:Animals; D001201:Ascites / Q000150:complications*; D001834:Body Water / Q000378:metabolism; D002251:Carbon Tetrachloride; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007527:Isoenzymes / Q000378:metabolism*; D020910:Ketorolac; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D007677:Kidney Function Tests; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000150:complications / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis*; D011720:Pyrazoles / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology*; D014046:Tolmetin / Q000031:analogs & derivatives / Q000494:pharmacology; D014556:Urine; D000096926:Benzenesulfonamides
D002251:Carbon Tetrachloride; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D020910:Ketorolac; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases; D011453:Prostaglandins; D011720:Pyrazoles; D012333:RNA, Messenger; D013449:Sulfonamides; D014046:Tolmetin; C119130:4-(5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide; D000096926:Benzenesulfonamides; C496513:Ptgs1 protein, rat