Treatment of experimental immune complex glomerulonephritis by sodium alginate.
We have studied the therapeutic efficacy of the sodium alginate in experimental immune complex glomerulonephritis. Bovine serum albumin (BSA) nephritis was induced in rats by a subcutaneous immunization and daily intravenous administration of BSA. Sodium alginate at two different doses (25 and 50 mg/kg) was administered intraperitoneally at regular 72-h intervals for 6 weeks. Onset of treatment was day 42. Urinary protein was measured weekly and serum anti-BSA antibody was assessed by ELISA method at different intervals. Animals were euthanized at the 12th experimental week and blood samples and kidney specimens were obtained. BUN, serum creatinine and serum cholesterol and triglyceride were measured at the time of sacrifice. Kidney specimens were processed for light and immunofluorescent microscopic examination. The tolerability and inhibitory effect of LVA on matrix metalloproteinase 2 (MMP-2) were tested using WEHI-164 cell line and zymography method. Results of this experiment showed that treatment with sodium alginate could significantly reduce the urinary protein excretion and serum creatinine in treated rats vs. nontreated controls. Anti-BSA antibody titers were lower in treated rats than in controls at the 12th week post-immunization. There was no significant difference in the level of BUN and serum lipids between two groups. Whereas, glomerular hypercellularity, PMN infiltration and glomerular deposition of BSA were less intense in treated rats vs. controls. Moreover, in vitro examinations revealed that treatment with LVA, as a very safe agent could diminish MMP-2 activity. These results suggest that treatment with sodium alginate as a new immunosuppressive agent can reduce proteinuria, inhibit MMP-2 activity and suppress the antibody production as well as the development of glomerular lesions in a rat model of immune complex glomerulonephritis.
Mirshafiey
Abbas
A
Department of Immunology, School of Public Health, Tehran University of Medical Sciences, P. O. Box 6446, 14155 Tehran, Iran. a_mirshafiey@yahoo.com
Borzooy
Zohreh
Z
Abhari
Reza Safari
RS
Razavi
Alireza
A
Tavangar
Mohammad
M
Rehm
Bernd H A
BH
D000464:Alginates / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000906:Antibodies / Q000032:analysis; D002151:Calorimetry; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D018093:Gelatinases / Q000378:metabolism; D005921:Glomerulonephritis / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D020723:Glucuronic Acid / Q000008:administration & dosage / Q000627:therapeutic use; D006603:Hexuronic Acids / Q000008:administration & dosage / Q000627:therapeutic use; D007105:Immune Complex Diseases / Q000188:drug therapy*; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000473:pathology; D007677:Kidney Function Tests; D008055:Lipids / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D012710:Serum Albumin, Bovine / Q000276:immunology
D000464:Alginates; D000906:Antibodies; D006603:Hexuronic Acids; D008055:Lipids; D012710:Serum Albumin, Bovine; D020723:Glucuronic Acid; D018093:Gelatinases