Abbas Mirshafiey, Salvatore Cuzzocrea, Bernd Rehm, Hidenori Matsuo
Med Sci Monit 2005; 11(8): PI53-63
Background: The tolerability and the anti-inflammatory and immunosuppressiveproperties of a novel designed non-steroidal anti-inflammatory drug, M2000 (beta-D-mannuronic acid),were investigated in various experimental models. Material/Methods: The anti-inflammatory and immunosuppressiveproperties of M2000 were tested in experimental models of rheumatoid arthritis (AIA) and multiple sclerosis(EAE). Its therapeutic potency on kidney diseases was studied using experimental models of nephrosisand immune complex glomerulonephritis (ICG). Biocompatibility and pharmacotoxicology assessment of M2000was carried out using a fibrosarcoma cell line, zymography, and serum and urine determinants. Results:Data showed that oral and/or i.p. administration of M2000 significantly reduces paw edema and histopathologicalparameters in arthritic rats. The immunosuppressive property of M2000 could significantly diminish clinicalsigns and histological erosions in the EAE model. Lymph node cell proliferation assay in EAE confirmedthe immunosuppressive efficacy of the tested drug. Our findings in ICG and experimental nephrosis showedthat M2000 enables a significant decrease in proteinuria, BUN, serum creatinine and cholesterol, as wellas glomerular lesion in M2000-treated rats. Moreover, this drug inhibited MMP-2 activity. The pharmacotoxicologystudy showed that M2000 is the safest anti-inflammatory and immunosuppressive drug in comparison withdexamethasone and conventional NSAIDs tested. Additionally, M2000 had no ulcerogenic effect on the ratstomach. Conclusions: M2000 is the first novel designed NSAID with the lowest molecular weight, no gastro-nephrotoxicity,and therapeutic effects in glomerulonephritis and nephrosis and could be strongly recommended on an extensivescale as the safest drug for decreasing anti-inflammatory reactions.
Keywords: Hydrocarbons - administration & dosage, Hydrocarbons - therapeutic use, Multiple Sclerosis - chemically induced, Animals, Anti-Inflammatory Agents, Non-Steroidal - therapeutic use, Antibodies - immunology, Arthritis, Experimental - pathology, Arthritis, Rheumatoid - pathology, Cattle, Cell Line, Tumor, Cell Proliferation - drug effects, Female, Glomerulonephritis - urine, Hindlimb - pathology, Hydrocarbons - therapeutic use, Immunosuppression, Interleukin-6 - metabolism, Lipids - blood, Male, Matrix Metalloproteinase 2 - metabolism, Mice, Multiple Sclerosis - pathology, Neurons - pathology, Rats, Rats, Inbred Lew, Serum Albumin, Bovine - immunology