Reduction of protein excretion by dimethyl sulfoxide in rats with passive Heymann nephritis

Passive Heymann nephritis, a model of immune complex nephritis, was produced in rats by injection of rabbit antibrush border membrane vesicle antibodies to examine the effect of treatment of epimembranous glomerulonephritis with dimethyl sulfoxide. Administration of DMSO twice a day, 5 days a week for 4 weeks significantly reduced protein excretion in the autologous phase of the model. This beneficial effect occurred in animals in which treatment was started a day after administration of the antibody and persisted for 4 weeks after treatment was discontinued. Serum triglyceride concentrations were significantly decreased, whereas, BUN, serum cholesterol, and globulin levels were significantly, but not reproducibly, reduced. That DMSO did not reduce proteinuria to normal values in rats treated after proteinuria was well established, but was able to reduce proteinuria significantly. Treatment of normal rats and those with nephrotoxic serum nephritis did not reduce protein excretion. Glomeruli of rats with passive Heymann nephritis treated with DMSO studied by immunofluorescent microscopy appeared to have less fluorescence for IgG than control rats, but these differences were not significant. However, C3 deposits were significantly decreased in treated rats, but only during the first week of the disease and in vitro C3 fixation was also significantly reduced in glomeruli of rats that had been treated with DMSO. There was very little effect on serum complement activity: CH50 was reduced only on day 1 of treatment, whereas the alternate pathway activity and serum C3 concentration were unaffected. DMSO may therefore reduce protein excretion, in part, by inhibiting C3-dependent proteinuria. These studies indicate that DMSO is capable of significantly reducing protein excretion in rats with passive Heymann nephritis and that its action may involve reduction of complement deposition within the glomeruli during the heterologous phase. Toxic effects included a 2.5% mortality and decreased weight gain while being treated with larger doses of DMSO. Treatment with a much smaller dose succeeded in reducing proteinuria significantly without affecting weight gain. There was no evidence of drug-induced liver or renal damage.