Enhanced in vivo lipid peroxidation in scleroderma spectrum disorders

Objective. A new family of prostaglandin F-2 isomers called F-2-isoprostane s, produced by free radical peroxidation of arachidonic acid, has recently been described in vivo. Its quantification has been suggested to be a relia ble measure of oxidant injury in vivo. The purpose of this study was to inv estigate urinary F-2-isoprostane formation as an index of lipid peroxidatio n in scleroderma spectrum disorders. Methods. Urine samples were obtained from 52 patients with systemic scleros is (SSc; n = 37) or undifferentiated connective tissue diseases (UCTD; n = 15) and from 20 healthy volunteers. Urinary isoprostaglandin F-2 alpha type III (iPF(2 alpha).III) and 11-dehydro thromboxane B-2 (11-dehydroTXB(2)) c oncentrations were determined using enzyme immunoassays. Results. The urinary concentration of iPF(2 alpha)-III was approximately tw ice as high in patients (mean +/- SEM 229 +/- 16 pmoles/mmoles creatinine) as in controls (116 +/- 9 pmoles/mmoles creatinine) (P < 0.0001). However, the urinary concentration of iPF(2<alpha>)-III was not significantly differ ent among patients with UCTD, limited SSc, and diffuse SSc (mean +/- SEM 22 1 +/- 27 versus 245 +/- 32 versus 220 +/- 25 pmoles/mmoles creatinine, resp ectively). No significant correlation was found between the urinary concent rations of iPF(2 alpha)-III and 11-dehydroTXB(2). Conclusion. This study provides evidence of enhanced lipid peroxidation in both SSc and UCTD, and suggests a rationale for antioxidant treatment of SS c. Formation of F-2-isoprostanes has to be investigated as a means for the evaluation of such therapy.