Effect of cyclosporin, indomethacin and methylprednisolone on puromycin-aminonucleoside induced nephrosis in rats

Kim, Hong Bae; Chung, Hae Lee; Ko, Cheol Woo; Koo, Ja Hoon; Gwak, Jung Sik

Abstract

This experimental study was conducted to evaluate the effect of indomethacin and methylprednisolone on PAN-induced nephrosis in rats. Sprague-Dawley rats weighing 150~200gm were used and divided into controls, group I (PAN intraperitoneally), group II(PAN intraperitoneally, followed by indomethacin peritoneally for 12 days), group III (PAN intraperitoneally, followed by methylprednisolone peritoneally for 12 days) and group IV (PAN intraperitoneally, followed by cyclosporin subcutaneously for 12 days). Twenty four-hour urinary protein excretion was measured on day 0, 5, 10 and 17. On the 17th day, rats were sacrificed for the determination of total serum protein, albumin and cholesterol levels. Foot process widths of glomerular epithelial cells were measured, and anionic sites of lamina rara externa were determined by using PEI as cationic probes. The following results were obtained. Twenty four-hour urinary protein excretion (mg/day) of group I was significantly increased to 455.7+/-188.8 on the 5th day compared to 15.2+/-3.7 on day 0 (p<0.01), and increased gradulally to 525.6+/-203.5 on the 10th day, then decreased to 280.6+/-25.2 on the 17th day. In group III, 24 hr urinary protein excretion on 17 th day (180.7+/-64.5) was significantly lower than that of group I (280.6+/-25.2). Total serum protein of group III was significantly lower than that of group I, and serum albumin and cholesterol did not show any significant difference among Group I, II, III and IV. Foot process widths (nm) of glomerular epithelial cells in group I, II, III and IV were 409.5+/-15.2, 387.8+/-49.2, 279.9+/-36.9 and 398.3+/-38.3, respectively. And the value of group of group III was significantly lower than that of group I (p<0.01). The number of anionic sites per 1micrometer length of glomerular basement membrane in Group I, II, III and IV were 10.3+/-1.3, 10.1+/-1.6, 12.5+/-1.5and 10.2+/-1.5, respectively. And the value of group III was significantly lower than that of group I (P<0.01). In conclusion, cyclosporin and indomethacin did not show any significant effect on PAN nephrosis in rat. However, methylprednisolone reduced the urinary protein excretion and showed significant recovery of foot process widths and number of anionic sites of glomerular basement membrane.