Scavengers of free radical oxygen affect the generation of low molecular weight DNA in stimulated lymphocytes from patients with systemic lupus erythematosus

• Published in: Metabolism, clinical and experimental Vol. 39; no. 12; p. 1278
• Main Authors: Benke, P J, Levcovitz, H, Paupe, J, Tozman, E
• Format: Journal Article
• Language: English
• Published: United States 01.12.1990
• Subjects: Adult; Cells, Cultured; Centrifugation, Density Gradient; Cysteamine - adverse effects; Cysteamine - pharmacology; DNA - metabolism; Free Radical Scavengers; Humans; Lupus Erythematosus, Systemic - blood; Lupus Erythematosus, Systemic - metabolism; Lymphocytes - metabolism; Molecular Weight; Oxygen - metabolism; Phytohemagglutinins - pharmacology
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1016/0026-0495(90)90184-E

Factors that potentially affect the generation of excess low molecular weight DNA (LMW-DNA) in cultured phytohemagglutinin (PHA)-stimulated lymphocytes of patients with systemic lupus erythematosus (SLE) were studied because this species of DNA is consistently found and this DNA may play a role in the pathogenesis of the disease. Superoxide dismutase (SOD; 0.05 mg/mL), a scavenger of free radical oxygen, decrease LMW-DNA formation in lymphocytes by 22%. Co-cultivation with cysteamine, a second scavenger of free radical oxygen and a sulfhydryl radioprotective agent, resulted in a 32% decrease in the generation of excess LMW-DNA at a concentration of 0.5 x 10(-3) mol/L and largely prevented its formation at 1.0 x 10(-3) mol/L. Other free radical scavengers (catalase, mannitol, vitamins C and E), cyclooxygenase inhibitors (ibuprofen and aspirin), a xanthine oxidase inhibitor (allopurinol), and an iron chelator (desferoxamine) did not affect excess LMW-DNA formation. Glutathione (1 x 10(-3) mol/L) had no effect and cysteine was toxic. Because scavengers of free radicals might be useful in the therapy of lupus, a trial of cysteamine (30 to 60 mg/kg/d) was administered to six acutely ill patients with SLE. A therapeutic benefit was not demonstrated, and some patients had exacerbation of disease. Lymphocyte cell growth from control and lupus subjects was stimulated when cysteamine, 1 x 10(-5) to 1 x 10(-4) mol/L was added to the media, but inhibited at concentrations of 2 x 10(-4) mol/L or greater. These studies suggest that the autooxidation and toxicity of high-dose cysteamine preclude its therapeutic use as a free radical scavenger.