Studies on antinephritic effect of mizoribine (p-INN, Bredinin), a new immunosuppressive agent, and azathioprine. (2) Effect on crescentic-type anti-GBM nephritis in rats. 1984

K Okamoto, and M Ito, and Y Suzuki

Crescentic-type nephritis was induced in rats by immunizing with rabbit gamma-globulin following i.v. injection of rabbit anti-rat glomerular basement membrane (anti-GBM) serum. The antinephritic effect of mizoribine was compared to that of azathioprine by administration from the 2nd day after the injection of anti-GBM serum to the 23rd day (Experiment I) and from the 15th to the 38th day (Experiment II). The experiment I assessment on the 24th day revealed that mizoribine at a dose of 7.5 mg/kg/day p.o. remarkably reduced plasma cholesterol level, wet kidney weight and glomerular histopathological changes (i.e., crescent formation and fibrinoid deposition). In addition, mizoribine at this dose also tended to reduce urinary protein excretion and the adhesion of capillary walls to Bowman's capsule. At a dose of 5 mg/kg/day p.o., mizoribine significantly reduced kidney weight and crescent formation. On the other hand, azathioprine at a dose of 20 mg/kg/day p.o. had a tendency to reduce these biochemical and histopathological parameters. In the experiment II assessment on the 39th day, the effects of both drugs were somewhat diminished compared to those in experiment I. Mizoribine strikingly inhibited the crescent formation with 5 and 7.5 mg/kg/day p.o. and inhibited the fibrinoid deposition with a dose of 7.5 mg/kg/day p.o. Azathioprine at a dose of 20 mg/kg/day p.o. was prone to reduce histopathological parameters. The above data indicate that mizoribine may be a useful new immunosuppressive agent for rapidly progressive glomerulonephritis, which is characterized by severe glomerular lesion with the extensive formation of crescents.

UI MeSH Term Description Entries
D007166 Immunosuppressive Agents Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging. Immunosuppressant,Immunosuppressive Agent,Immunosuppressants,Agent, Immunosuppressive,Agents, Immunosuppressive
D007678 Kidney Glomerulus A cluster of convoluted capillaries beginning at each nephric tubule in the kidney and held together by connective tissue. Glomerulus, Kidney
D008297 Male Males
D011919 Rats, 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. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
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
D001327 Autoimmune Diseases Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides. Autoimmune Disease,Disease, Autoimmune,Diseases, Autoimmune
D001379 Azathioprine An immunosuppressive agent used in combination with cyclophosphamide and hydroxychloroquine in the treatment of rheumatoid arthritis. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), this substance has been listed as a known carcinogen. (Merck Index, 11th ed) Azathioprine Sodium,Azathioprine Sodium Salt,Azathioprine Sulfate,Azothioprine,Immuran,Imuran,Imurel,Sodium, Azathioprine
D001485 Basement Membrane A darkly stained mat-like EXTRACELLULAR MATRIX (ECM) that separates cell layers, such as EPITHELIUM from ENDOTHELIUM or a layer of CONNECTIVE TISSUE. The ECM layer that supports an overlying EPITHELIUM or ENDOTHELIUM is called basal lamina. Basement membrane (BM) can be formed by the fusion of either two adjacent basal laminae or a basal lamina with an adjacent reticular lamina of connective tissue. BM, composed mainly of TYPE IV COLLAGEN; glycoprotein LAMININ; and PROTEOGLYCAN, provides barriers as well as channels between interacting cell layers. Basal Lamina,Basement Lamina,Lamina Densa,Lamina Lucida,Lamina Reticularis,Basement Membranes,Densas, Lamina,Lamina, Basal,Lamina, Basement,Lucida, Lamina,Membrane, Basement,Membranes, Basement,Reticularis, Lamina
D012263 Ribonucleosides Nucleosides in which the purine or pyrimidine base is combined with ribose. (Dorland, 28th ed)

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