The
prostaglandin cyclooxygenase (Cox) exists in two
isoforms with different genetic representation. The
isoform, which is constitutively expressed (Cox 1), and mediates physiological functions of
prostaglandins, and the inducible
isoform (Cox 2) which is upregulated by inflammatory stimuli. This study attempts to determine whether a Cox 2 selective inhibitor,
flosulide, differs from the mixed type Cox 1 and
Cox 2 inhibitor aspirin in respect of renal function and
eicosanoid excretion in experimental
nephritis. The effects of
flosulide and
aspirin were studied during the autologous phase of passive
Heymann nephritis (PHN) in rats. Female Wistar rats were injected i.v. with 1 ml of Fx1A antiserum at day 1. From day 7 to day 14 they received either
aspirin (
aspirin, 50 mg/day),
flosulide, (0.75 mg/day) or vehicle p.o. The kidney function was evaluated and the animals sacrificed. The kidneys were removed and glomeruli isolated. The glomeruli were incubated in physiological
buffer solution. Basal
prostaglandin generation was determined in the supernatant. Treatment with
flosulide significantly reduced
proteinuria as compared to
aspirin treatment (64+/-15 vs. 109+/-14 mg/24 h, p < 0.05).
Plasma protein and
albumin levels were significantly lower in the
aspirin-treated group than in
flosulide-treated animals (4.7+/-0.26 vs. 5.48+/-0.08 mg/dl, p < 0. 05 and 0.96+/-0.04 vs. 1.25+/-0.10 mg/dl, p < 0.05). Glomerular
prostaglandin production (6-keto-PGF1alpha, TxB2, Bicyclo-PGE2) was significantly reduced in
aspirin-, but not in
flosulide-treated animals. This was mainly due to a reduction of glomerular TxB2 production by
aspirin. Our data demonstrate that a Cox 2 selective inhibitor of
prostaglandin formation,
flosulide, has beneficial effects on preservation of kidney function in rats with PHN, whereas
aspirin has not. These beneficial effects of
flosulide possibly result from preservation of the physiological glomerular
prostaglandin production. Thus, selective
Cox 2 inhibitors might be interesting substances for treatment of
nephrotic syndrome.