Immunohistochemical localisation of renal cyclooxygenase-1 expression in non-steroidal anti-inflammatory drug-treated mice.
The utility of cyclooxygenase-inhibiting non-steroidal anti-inflammatory drugs is limited by unwanted side effects that include disturbances in renal function. In order to further understand the mechanisms that underlie these renal side effects, the expression of the prostaglandin-synthesizing enzyme cyclooxygenase (COX) was examined by immunohistochemical methods in murine kidneys after treatment with indomethacin, a non-selective inhibitor or nimesulide, an inhibitor that preferentially and selectively blocks the COX-2 isoform of the enzyme. In untreated control kidneys, COX-1 protein was expressed in the glomeruli and parietal cells of the glomerular capsule, epithelial cells of the proximal and distal convoluted tubules including the juxtaglomerular region, and the collecting ducts. At therapeutic doses, indomethacin (10mg/kg) did not alter renal COX-1 expression relative to immunoreactivity in untreated control kidney. By contrast, an equipotent therapeutic dose of nimesulide reduced renal COX-1 expression within the first 24h of treatment. Taken together with the reports of reduced COX-1 expression prior to renal tissue damage following high-dose indomethacin treatment, our findings suggest that effects of NSAIDs on renal COX expression are dependent on dose and may be related to isoform specificity.
School of Nursing, Midwifery and Health Systems, University College Dublin, Belfield, Dublin 4, Ireland.
Marie
M
Meskell
Raj
R
Ettarh
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D051545:Cyclooxygenase 1 / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D007150:Immunohistochemistry; D007213:Indomethacin / Q000009:adverse effects*; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D007672:Kidney Cortex / Q000187:drug effects / Q000201:enzymology; D007679:Kidney Medulla / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D013449:Sulfonamides / Q000009:adverse effects*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D013449:Sulfonamides; D051545:Cyclooxygenase 1; C012655:nimesulide; D007213:Indomethacin