Selective inhibition of cyclooxygenase 2 spares renal function and prostaglandin synthesis in cirrhotic rats with ascites

Gastroenterology. 1999 May;116(5):1167-75. doi: 10.1016/s0016-5085(99)70020-x.

Abstract

Background & aims: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ascites / complications*
  • Body Water / metabolism
  • Carbon Tetrachloride
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / pharmacology
  • Glomerular Filtration Rate / drug effects
  • Hemodynamics / drug effects
  • Isoenzymes / metabolism*
  • Ketorolac
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney / physiology*
  • Kidney Function Tests
  • Liver Cirrhosis, Experimental / chemically induced
  • Liver Cirrhosis, Experimental / complications
  • Liver Cirrhosis, Experimental / metabolism*
  • Male
  • Membrane Proteins
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • Prostaglandins / biosynthesis*
  • Pyrazoles / pharmacology*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Sulfonamides / pharmacology*
  • Tolmetin / analogs & derivatives
  • Tolmetin / pharmacology
  • Urine

Substances

  • 4-(5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Isoenzymes
  • Membrane Proteins
  • Prostaglandins
  • Pyrazoles
  • RNA, Messenger
  • Sulfonamides
  • Carbon Tetrachloride
  • Tolmetin
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Ptgs1 protein, rat
  • Ketorolac