1617 PREVENTION BY DMSO OF GLOMERULAR INJURY IN NZB/WF1 LUPUS MICE

Abstract

Dimethyl sulfoxide (DMSO) was given to NZB/WF1 lupus mice from 10 weeks of age to see if proteinuria could be prevented in this model of glomerular injury. Twenty mice were randomized into saline (0.1 ml/day) and DMSO treatment groups (DMSO 4 mg/gm/day). Significant differences in urine protein excretion between controls and treated groups were evident at 5 months (DMSO: 5.5 ± 0.46 mg/24 hrs; Controls: 7.35 ± 0.59 mg/24 hrs; p < 0.05) and at 6.5 months of age (DMSO: 6.75 ± 0.73 mg/24 hrs; Controls: 15 ± 2.15 mg/24 hrs; p < 0.01). By 7 and 7.5 months, the protein excretion was not significantly different (DMSO: 18 ± 8.3 mg/24 hrs; Controls: 41 ± 8.7 mg/24 hrs; p > 0.05); 7.5 months: DMSO: 20 ± 7.4 mg/24 hrs; Controls: 29 ± 5.7 mg/24 hrs; p > 0.05. However, the urine protein:creatinine ratio was significantly reduced in DMSO treated mice compared to controls at 6.5 months (DMSO: 13.4 ± 1.32; Controls: 24.4 ± 4.2; p < 0.05), at 7 months (DMSO: 46.7 ± 23; Controls: 101 ± 28; p < 0.05), and at 7.5 months of age (DMSO: 37 ± 13; Controls: 88 ± 31; p < 0.05). The mean serum creatinine values were significantly lower at 7.5 months of age in DMSO treated mice (0.41 ± 0.08 mg/dl) compared to controls (0.91 ± 0.56 mg/dl; p < 0.05). By 7.5 months of age, 5/6 treated mice had relatively normal renal histology on light microscopy, while 6/8 untreated had focal proliferative glomeruloneprhtis, crescents and glomerular obsolescence (p <0.02). These findings demonstrate that DMSO has a protective effect on the progression of glomerular injury in this model.