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Amelioration of murine lupus nephritis by dimethylsulfoxide
L S Milner1, J P de Chadarévian, P R Goodyer
1Renal Service-Renal Laboratory, Montreal Children's Hospital, Quebec, Canada.
Abstract:
Dimethylsulfoxide was given to NZB/W F1 female mice from age 10 weeks to see if proteinuria and glomerular injury could be reduced. Twenty mice were randomly assigned to saline or DMSO treatment groups and the following studies were done: urine protein determination, serum concentrations of creatinine, IgG, C3, and albumin; and ANA titers. Kidney tissue were studied by light, immunofluorescent and electron microscopy. DMSO-treated mice had significant reductions in protein excretion at 5 and 6.5 months of age; in urine protein/creatinine ratio at 6.5, 7, and; 7.5 months; in serum C3 at 7.5 months; and in serum creatinine concentration. There were no significant differences among serum IgG, nor among the ANA titers. Histopathologic studies revealed nearly normal kidneys in 5/6 DMSO-treated mice whereas 4/8 controls had severe mixed membranous and membranoproliferative glomerulonephritis. Ultrastructural studies revealed mesangial, subendothelial, and subepithelial deposits and membranous transformation of the glomerular capillary wall. DMSO therefore appears capable of ameliorating glomerular injury in NZB/W F1 mice.
Insights
Dimethyl sulfoxide (DMSO) treatment significantly reduced proteinuria and glomerular injury in NZB/W F1 mice. This study suggests DMSO may ameliorate kidney damage in lupus-prone mice.
Area of Science:
- Nephrology
- Immunology
- Pharmacology
Background:
- NZB/W F1 mice spontaneously develop lupus nephritis, characterized by proteinuria and glomerular injury.
- Early intervention is crucial for managing lupus nephritis progression.
Purpose of the Study:
- To investigate the therapeutic potential of dimethyl sulfoxide (DMSO) in ameliorating proteinuria and glomerular injury in NZB/W F1 female mice.
Main Methods:
- NZB/W F1 female mice were treated with DMSO or saline from 10 weeks of age.
- Evaluated urine protein, serum creatinine, C3, albumin, and ANA titers.
- Kidney tissues were analyzed using light, immunofluorescence, and electron microscopy.
Main Results:
- DMSO treatment led to significant reductions in proteinuria and urine protein/creatinine ratio.
- DMSO-treated mice showed decreased serum creatinine and C3 levels.
- Histopathological analysis revealed significantly less glomerular damage in DMSO-treated mice compared to controls.
Conclusions:
- Dimethyl sulfoxide demonstrates a protective effect against lupus nephritis progression in NZB/W F1 mice.
- DMSO ameliorates key pathological features of glomerular injury, including proteinuria and inflammation.