Effect of dimethylsulfoxide on sphingomyelinase activity and cholesterol metabolism in Niemann-Pick type C fibroblasts

Abstract

Niemann-Pick type C (NPC) fibroblasts present a large concentration of cholesterol in their cytoplasm due to a still unidentified deficiency in cholesterol metabolism. The influence of dimethylsulfoxide (DMSO) on the amount of intracellular cholesterol was measured in 8 cultures of normal fibroblasts and in 7 fibroblast cultures from NPC patients. DMSO was added to the fibroblast cultures at three different concentrations (1, 2 and 4%, v/v) and the cultures were incubated for 24 h. Sphingomyelinase activity was significantly increased in both groups of cells only when incubated with 2% DMSO (59.4 ± 9.1 and 77.0 ± 9.1 nmol h -1 mg protein -1 , controls without and with 2% DMSO, respectively; 47.7 ± 5.2 and 55.8 ± 4.1 nmol h -1 mg protein -1 , NPC without and with 2% DMSO, respectively). However, none of the DMSO concentrations used altered the amount of cholesterol in the cytoplasm of NPC cells (0.704 ± 0.049, 0.659 ± 0.041, 0.688 ± 0.063 and 0.733 ± 0.088 mg/mg protein, without DMSO, 1% DMSO, 2% DMSO and 4% DMSO, respectively). This finding suggests that sphingomyelinase deficiency is a secondary defect in NPC and shows that DMSO failed to remove the stored cholesterol. These data do not support the use of DMSO in the treatment of NPC patients. Correspondence

Dimethyl Sulfoxide and Oxidative Stress On Cultures of Human Keratinocytes

“…Several experiments with skin flaps (19), egg cell cultures (20), hepatocytes (21)(22)(23)(24), macrophages (25), fibroblasts (5) and keratinocytes from the cornea (26) were performed under the action of DMSO at 1% to 4% concentrations. These studies reported the influence of DMSO on cellular proliferation and differentiation.…”

Dimethyl sulfoxide and oxidative stress on cultures of human keratinocytes

“…Several studies contributed to formulating a culture medium that stimulated the proliferation of keratinocytes (3)(4)(5)(6)(7). However, only a few studies in the literature report the use of substances that may protect laboratory-grown keratinocytes from damaging factors.…”