Indomethacin-induced morphologic changes in the rat urinary bladder epithelium.
OBJECTIVE
To evaluate the morphologic changes in rat urothelium induced by indomethacin. Nonsteroidal anti-inflammatory drug-induced cystitis is a poorly recognized and under-reported condition. In addition to tiaprofenic acid, indomethacin has been reported to be associated with this condition.


METHODS
Three groups were established: a control group (n = 10), a high-dose group (n = 10), treated with one intraperitoneal injection of indomethacin 20 mg/kg, and a therapeutic dose group (n = 10) in which oral indomethacin was administered 3.25 mg/kg body weight daily for 3 weeks. The animals were then killed and the bladders removed for light and electron microscopic studies.


RESULTS
The light microscopic findings showed some focal epithelial degeneration that was more prominent in the high-dose group. When compared with the control group, both indomethacin groups revealed statistically increased numbers of mast cells in the mucosa (P <0.0001) and penetration of lanthanum nitrate through intercellular areas of the epithelium. Furthermore, the difference in mast cell counts between the high and therapeutic dose groups was also statistically significant (P <0.0001).


CONCLUSIONS
Indomethacin resulted in histopathologic findings typical of interstitial cystitis, such as leaky bladder epithelium and mucosal mastocytosis. The true incidence of nonsteroidal anti-inflammatory drug-induced cystitis in humans must be clarified by prospective clinical trials.
Cetinel
Sule
S
Department of Histology and Embryology, Marmara University School of Medicine, Haydarpaşa, Istanbul, Turkey.
Cetinel
B lent
Bl
Ercan
Feriha
F
Hrda
Canan
C
San
Tangl
T
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000494:pharmacology; D002452:Cell Count; D018856:Cystitis, Interstitial / Q000139:chemically induced / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D007213:Indomethacin / Q000009:adverse effects* / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008407:Mast Cells / Q000166:cytology; D008415:Mastocytosis / Q000139:chemically induced* / Q000473:pathology; D008855:Microscopy, Electron, Scanning; D051381:Rats; D017207:Rats, Sprague-Dawley; D001743:Urinary Bladder / Q000187:drug effects / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000473:pathology*; D019459:Urothelium / Q000187:drug effects / Q000473:pathology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007213:Indomethacin