Scavengers of free radical oxygen affect the generation of low molecular weight DNA in stimulated lymphocytes from patients with systemic lupus erythematosus.
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.
Benke
P J
PJ
Mailman Center, University of Miami School of Medicine, FL 33101.
Levcovitz
H
H
Paupe
J
J
Tozman
E
E
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
D016166:Free Radical Scavengers; D010835:Phytohemagglutinins; D003543:Cysteamine; D004247:DNA; D010100:Oxygen