Enhanced in vivo lipid peroxidation in scleroderma spectrum disorders

Abstract

Objective: A new family of prostaglandin F2 isomers called F2-isoprostanes, produced by free radical peroxidation of arachidonic acid, has recently been described in vivo. Its quantification has been suggested to be a reliable measure of oxidant injury in vivo. The purpose of this study was to investigate urinary F2-isoprostane formation as an index of lipid peroxidation in scleroderma spectrum disorders.

Methods: Urine samples were obtained from 52 patients with systemic sclerosis (SSc; n = 37) or undifferentiated connective tissue diseases (UCTD; n = 15) and from 20 healthy volunteers. Urinary isoprostaglandin F2alpha type III (iPF2alpha-III) and 11-dehydro thromboxane B2 (11-dehydroTXB2) concentrations were determined using enzyme immunoassays.

Results: The urinary concentration of iPF2alpha-III was approximately twice 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 iPF2alpha-III was not significantly different among patients with UCTD, limited SSc, and diffuse SSc (mean +/- SEM 221+/-27 versus 245+/-32 versus 220+/-25 pmoles/mmoles creatinine, respectively). No significant correlation was found between the urinary concentrations of iPF2alpha-III and 11-dehydroTXB2.

Conclusion: This study provides evidence of enhanced lipid peroxidation in both SSc and UCTD, and suggests a rationale for antioxidant treatment of SSc. Formation of F2-isoprostanes has to be investigated as a means for the evaluation of such therapy.