title: Scavengers of free radical oxygen affect the generation of low molecular weight DNA in stimulated lymphocytes from patients with systemic lupus erythematosus.
abstract: 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.
authors: Mailman Center, University of Miami School of Medicine, FL 33101.
authors: P J
authors: PJ
authors: Benke
authors: H
authors: H
authors: Levcovitz
authors: J
authors: J
authors: Paupe
authors: E
authors: E
authors: Tozman
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D002499:Centrifugation, Density Gradient; D003543:Cysteamine / Q000009:adverse effects / Q000494:pharmacology; D004247:DNA / Q000378:metabolism*; D016166:Free Radical Scavengers; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism*; D008970:Molecular Weight; D010100:Oxygen / Q000378:metabolism*; D010835:Phytohemagglutinins / Q000494:pharmacology
chemical_list: D016166:Free Radical Scavengers; D010835:Phytohemagglutinins; D003543:Cysteamine; D004247:DNA; D010100:Oxygen