MECHANISM OF ACTION OF CYCLOPHOSPHAMIDE ON NEPHRITIS OF (NZB BY NZW)F1 HYBRID MICE
- 1 January 1977
- journal article
- research article
- Vol. 29 (1), 132-139
Abstract
The effects of cyclophosphamide on antinuclear antibody levels, immune complex deposition in renal glomeruli, glomerular cell proliferation and glomerulosclerosis in the (NZB .times. NZW)F1 hybrid mouse was investigated to better understand the mechanism of action of this drug on nephritis. Five groups of mice were injected daily with this agent (15 mg/kg) by the i.p. route over a 2 mo. period. Treatment periods began at 1, 3, 5, 7 and 9 mo. Each group was killed at the end of the treatment period. During the last week 3H-Tdr [thymidine] (1 .mu.Ci/g) was injected daily i.p. Immune complex deposition was measured by quantification of glomerular immunofluorescent staining in both capillary loops and mesangium. Glomerular cell proliferation was quantified by measurement of the number of glomerular cells which incorporated 3H-Tdr during in vivo labeling. The number of 3H-Tdr-labeled cells in each of 100 glomeruli was counted using kidney autoradiographs of whole kidney slices. This technique provided a very reproducible and quantitative index of glomerular cell proliferation. Glomerulosclerosis was measured by determining percentage of PAS[periodic-acid Schiff]-positive material in each of 100 counted glomeruli. Immune complex deposition in the kidney preceded the glomerular cell proliferation. The proliferation reached a peak at 9 mo. of age. Glomerulosclerosis gradually increased with age until the animal''s death. Cyclophosphamide significantly decreased antinuclear antibody levels, glomerular cell proliferation and immunoglobulin staining in the glomeruli. Progression of glomerulosclerosis was significantly arrested. A very significant effect of cyclophosphamide is demonstrated on 3 important pathological changes which occur in the nephritis of the (NZB .times. NZW)F1 hybrid mouse and provide information about possible mechanisms underlying these changes.This publication has 9 references indexed in Scilit:
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