Nitroflurbiprofen, a new nonsteroidal anti-inflammatory, ameliorates structural injury in the remnant kidney.
Cyclooxygenase derivatives and nitric oxide (NO) may influence the pathogenesis of progressive nephropathies. We investigated the effect of nitroflurbiprofen (NOF), a NO-releasing nonsteroidal anti-inflammatory drug (NSAID) without gastrointestinal toxicity, in rats with 5/6 ablation (NX). The following four groups were studied: Sham, sham-operated rats; Sham + NOF, Sham receiving oral NOF two times daily; NX, rats subjected to NX; and NX + NOF, NX receiving NOF. NOF was barely detected in plasma but released the parent compound flurbiprofen. At 30 days, glomerular hydraulic pressure (PGC) was 76 +/- 3 mmHg in NX (52 +/- 1 in Sham, P < 0.05). NOF slightly reduced PGC to 69 +/- 2 mmHg in NX + NOF (P > 0.05 vs. NX). Glomerular volumes behaved similarly. At 60 days, tail cuff pressure was 152 +/- 6 mmHg, glomerulosclerosis index was 22.1 +/- 9.5, and interstitial fractional area was 9.9 +/- 1.2% in NX. NOF reduced these parameters to 137 +/- 4 mmHg, 3.5 +/- 0.7, and 6.4 +/- 0.8%, respectively (P < 0.05), without causing growth stunting or anemia. These beneficial effects could not be ascribed to NO donation and may reflect cyclooxygenase inhibition. This is the first evidence that chronic NSAID treatment may ameliorate progressive nephropathies.
Fujihara
C K
CK
Department of Clinical Medicine, University of São Paulo School of Medicine, Brazil.
Malheiros
D M
DM
Donato
J L
JL
Poli
A
A
De Nucci
G
G
Zatz
R
R
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology; D005480:Flurbiprofen / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D005923:Glomerulosclerosis, Focal Segmental / Q000503:physiopathology / Q000517:prevention & control; D006439:Hemodynamics / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009392:Nephrectomy; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; C095631:nitroflurbiprofen; D009569:Nitric Oxide; D005480:Flurbiprofen