EFFECT OF LIPO-PROSTAGLANDIN E-1 ON CRESCENTIC-TYPE ANTIGLOMERULAR BASEMENT-MEMBRANE NEPHRITIS IN RATS

The antinephritic effect of lipo-prostaglandin E-1, prostaglandin E-1 2-[(E)-(3S)-3-hydroxy-1-octenyl]-5-oxocyclopentane heptanoic acid) inc orporated in lipid microspheres was investigated using an experimental model of nephritis, crescentic-type anti-glomerular basement membrane nephritis. Lipo-prostaglandin E-1 was given i.v. twice a day at 20, 4 0 and 80 mu g/kg and azathioprine, an immunosuppressive agent, at 20 m g/kg was given p.o. once daily from the autologous phase, in which glo merulonephritis was fully developed (the 21st day after injection of t he anti-glomerular basement membrane serum), to the 50th day. Lipo-pro staglandin E, (40 and 80 mu g/kg x 2 per day) significantly inhibited the development of glomerular alterations as well as the elevation of proteinuria and plasma creatinine. Lipo-prostaglandin E-1 (20 mu g/kg x 2 per day) and azathioprine (20 mg/kg per day) significantly inhibit ed only the glomerular histopathological changes. Lipo-prostaglandin E , at three doses significantly decreased the deposition of both rabbit immunoglobulin G and rat immunoglobulin G on the glomerular basement membrane in nephritic rats, but azathioprine apparently inhibited only the deposition of rat immunoglobulin G. A single administration of li po-prostaglandin E, inhibited the elevation of platelet aggregation an d restored the decrease in renal tissue blood flow in nephritic rats. In addition, a single administration of lipo-prostaglandin E-1 inhibit ed the elevation of glomerular thromboxane B-2 and 6-keto prostaglandi n F-1 alpha production in nephritic rats. These results suggest that l ipo-prostaglandin E-1 may be an effective agent for the treatment of g lomerulonephritis. Its antinephritic effect may be due to the inhibiti on of platelet aggregation, an increase in renal tissue blood flow, a decrease in rabbit and rat immunoglobulin G deposition, and ameliorati on of the abnormal metabolism of arachidonic acid. (C) 1998 Elsevier S cience B.V.