Dimethyl sulfoxide modulation of diabetes onset in NOD mice.
Dimethyl sulfoxide (DMSO), a hydroxyl radical scavenger, is known as an immunosuppressive agent and can reduce autoantibody levels in experimental autoimmune diseases. Because classic diabetogens damage the DNA and membrane of the beta-cell by the generation of free radicals, the purpose of these investigations was to determine whether the intake of DMSO or its derivatives methylsulfonylmethane (MSM) and dimethylsulfide (DMS) could prevent the expression of autoimmune diabetes in the spontaneously diabetic NOD mouse. DMSO (2.5%), MSM (2.5%), and DMS (0.25%) were added to the drinking water of female NOD mice immediately after weaning. Control animals were maintained on regular drinking water. The presence of overt diabetes was monitored from the age of 2 mo by weekly urinary glucose testing until the animals either became overtly glucosuric or were greater than 240 days of age. In contrast to what we expected, DMSO (2.5%) markedly increased the rate at which the animals expressed overt diabetes (P less than .0004, log-rank test). MSM had no effect, whereas DMS reduced the incidence and rate of diabetes onset. When DMSO (2.5%) was administered to male NOD mice and control strains of mice (BALB/c and ICR), the control group did not develop glucosuria or insipidus, whereas DMSO increased the incidence of diabetes in the male NOD mice from 21 to 79%. In contrast, when DMSO was fed to female NOD mice on a purified AIN-76 diet, diabetes onset was reduced to 36%. We conclude that DMSO accelerates the uptake of dietary diabetogens into the beta-cell of genetically susceptible animals (NOD mice). The protective effect of the purified diet in such animals may be due to a lack of putative diabetogens in purified diet, or alternatively, the diet itself contains factor(s) that protect the beta-cell from autoimmune attack and/or destruction.
Klandorf
H
H
Department of Medicine, University of California, Los Angeles School of Medicine.
Chirra
A R
AR
DeGruccio
A
A
Girman
D J
DJ
D000818:Animals; D001327:Autoimmune Diseases / Q000517:prevention & control; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D004121:Dimethyl Sulfoxide / Q000627:therapeutic use*; D005260:Female; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D008817:Mice, Mutant Strains; D012016:Reference Values; D013440:Sulfides / Q000627:therapeutic use*; D013450:Sulfones / Q000627:therapeutic use*
D007166:Immunosuppressive Agents; D013440:Sulfides; D013450:Sulfones; C025910:dimethyl sulfone; C004784:dimethyl sulfide; D004121:Dimethyl Sulfoxide