Biomaterial Database

The mechanism of action of cyclophosphamide on the nephritis of (NZB x NZW)F1 hybrid mice. 1977

E R Hurd, and M Ziff

The effects of cyclophosphamide an antinuclear antibody levels, immune complex deposition in renal glomeruli, glomerular cell proliferation and glomerulosclerosis in the (NZB x NZW)F1 hybrid mouse have been investigated in order 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-month period. Treatment periods began at 1, 3, 5, 7 and 9 months. Each group was killed at the end of the treatment period. During the last week [3H]Tdr(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 labelling. The number of [3H]Tdr-labelled 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-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 months 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. The present findings demonstrate a very significant effect of cyclophosphamide on three important pathological changes which occur in the nephritis of the (NZB x NZW)F1 hybrid mouse and provide information about possible mechanisms underlying these changes.

UI	MeSH Term	Description	Entries
D007668	Kidney	Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.	Kidneys
D007678	Kidney Glomerulus	A cluster of convoluted capillaries beginning at each nephric tubule in the kidney and held together by connective tissue.	Glomerulus, Kidney
D008815	Mice, Inbred Strains	Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.	Inbred Mouse Strains,Inbred Strain of Mice,Inbred Strain of Mouse,Inbred Strains of Mice,Mouse, Inbred Strain,Inbred Mouse Strain,Mouse Inbred Strain,Mouse Inbred Strains,Mouse Strain, Inbred,Mouse Strains, Inbred,Strain, Inbred Mouse,Strains, Inbred Mouse
D009393	Nephritis	Inflammation of any part of the KIDNEY.	Nephritides
D003520	Cyclophosphamide	Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer.	(+,-)-2-(bis(2-Chloroethyl)amino)tetrahydro-2H-1,3,2-oxazaphosphorine 2-Oxide Monohydrate,B-518,Cyclophosphamide Anhydrous,Cyclophosphamide Monohydrate,Cyclophosphamide, (R)-Isomer,Cyclophosphamide, (S)-Isomer,Cyclophosphane,Cytophosphan,Cytophosphane,Cytoxan,Endoxan,NSC-26271,Neosar,Procytox,Sendoxan,B 518,B518,NSC 26271,NSC26271
D005260	Female		Females
D005921	Glomerulonephritis	Inflammation of the renal glomeruli (KIDNEY GLOMERULUS) that can be classified by the type of glomerular injuries including antibody deposition, complement activation, cellular proliferation, and glomerulosclerosis. These structural and functional abnormalities usually lead to HEMATURIA; PROTEINURIA; HYPERTENSION; and RENAL INSUFFICIENCY.	Bright Disease,Kidney Scarring,Glomerulonephritides,Scarring, Kidney
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000936	Antigen-Antibody Complex	The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes IMMUNE COMPLEX DISEASES.	Immune Complex,Antigen-Antibody Complexes,Immune Complexes,Antigen Antibody Complex,Antigen Antibody Complexes,Complex, Antigen-Antibody,Complex, Immune,Complexes, Antigen-Antibody,Complexes, Immune
D000974	Antibodies, Antinuclear	Autoantibodies directed against various nuclear antigens including DNA, RNA, histones, acidic nuclear proteins, or complexes of these molecular elements. Antinuclear antibodies are found in systemic autoimmune diseases including systemic lupus erythematosus, Sjogren's syndrome, scleroderma, polymyositis, and mixed connective tissue disease.	Anti-DNA Antibodies,Antibodies, Anti-DNA,Antinuclear Antibodies,Antinuclear Autoantibodies,Antinuclear Autoantibody,Antinuclear Factors,Antinuclear Antibody,Antinuclear Factor,Anti DNA Antibodies,Antibody, Antinuclear,Autoantibody, Antinuclear,Factor, Antinuclear