ozagrel and Nephrotic-Syndrome

The administration of the aminonucleoside of puromycin (PAN) to rats causes the nephrotic syndrome that is associated with an acute decline in renal function, and an interstitial infiltrate. We examined whether essential fatty acid deficiency (EFAD), which inhibits macrophage infiltration in glomerulonephritis, affects PAN-induced renal dysfunction. Both control and EFAD rats developed proteinuria that resolved over 28 d. After PAN administration, there was a prominent infiltration of macrophages in rats fed a normal diet. The infiltrate was prevented by the EFAD diet. The absence of a macrophage interstitial infiltrate was associated with a significantly higher Cin in the EFAD rats than in controls at 7 d (5.21 +/- 1.19 versus 0.39 +/- 0.08, P less than 0.002 ml/min/kg BW). In addition, CPAH fell to less than 10 ml/min/kg BW by day 7 in controls, but remained the same as normal in the EFAD. After administration of PAN to control rats, there was no increase in urinary thromboxane excretion or an increase in glomerular thromboxane production. Furthermore, the effect of EFAD could not be mimicked by the administration of a thromboxane synthase inhibitor. Irradiation-induced leukopenia in rats on a normal diet markedly improved glomerular filtration and renal blood flow in acutely nephrotic rats. EFAD prevents the interstitial cellular infiltrate and the renal ischemia associated with experimental nephrosis. The recruitment of mononuclear cells into the kidney following PAN directly contributes to the decline in renal function.

Topics: Acute Disease; Animals; Fatty Acids, Essential; Female; Kidney; Kidney Diseases; Leukopenia; Macrophages; Methacrylates; Nephrotic Syndrome; Puromycin Aminonucleoside; Rats; Rats, Inbred Lew; Thromboxane B2

To determine if a selective thromboxane (TX)A2 synthetase inhibitor is clinically effective for the treatment of nephrotic syndrome, 11 patients with nephrotic syndrome were treated only with OKY-046, (E)-3-4-(1-imidazolylmethyl)phenyl-2-propenoic acid hydrochloride monohydrate, for at least 8 weeks. Urinary excretion of protein, TXB2, 2,3-dinor-TXB2, and beta-N-acetyl-D-glucosaminidase decreased with OKY-046. Creatinine clearance value, and urinary excretion of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), however, did not show any significant change, while serum albumin level increased. Two patients with minimal change nephrotic syndrome showed complete remission only with OKY-046. These results demonstrate that the selective TXA2 synthetase inhibitor is an effective drug for the treatment of chronic glomerulonephritis accompanied by nephrotic syndrome.

Topics: 6-Ketoprostaglandin F1 alpha; Acrylates; Adolescent; Adult; Aged; Female; Glomerulonephritis; Humans; Male; Methacrylates; Middle Aged; Nephrosis, Lipoid; Nephrotic Syndrome; Proteinuria; Thromboxane B2; Thromboxane-A Synthase

Topics: Acrylates; Animals; Male; Methacrylates; Nephrotic Syndrome; Proteinuria; Puromycin Aminonucleoside; Rats; Rats, Inbred Strains; Thromboxane-A Synthase