Chronic obstructive pulmonary disease is associated with an increase in urinary levels of isoprostane F2alpha-III, an index of oxidant stress

Am J Respir Crit Care Med. 1998 Dec;158(6):1709-14. doi: 10.1164/ajrccm.158.6.9709066.

Abstract

Oxidative stress has been suggested as a potential mechanism in the pathogenesis of chronic obstructive pulmonary disease (COPD). It has been difficult to address this hypothesis because of the limitations of conventional indices of lipid peroxidation in vivo. F2-isoprostanes (iPs) are prostaglandin isomers formed by free radical dependent peroxidation of arachidonic acid. Urinary iPF2alpha-III is a relatively abundant iPs produced in humans. In the present study, we investigated whether COPD is associated with enhanced oxidative stress by measuring urinary levels of this compound. Urinary excretion of iPF2alpha-III was determined in 38 patients with COPD and 30 sex- and age-matched healthy control subjects. Levels of iPF2alpha-III were significantly higher in patients with COPD (median, 84 pmol/ mmol creatinine; range, 38 to 321) than in healthy controls (median, 35.5 pmol/mmol creatinine; range, 15 to 65) (p < 0.0001). This elevation was independent of age, sex, smoking history, or duration of the disease. An inverse relationship was observed with the level of PaO2 (r = -0.38, p = 0. 019). Aspirin treatment failed to decrease urinary levels of iPF2alpha-III (102 +/- 8 versus 99.2 +/- 7.3 pmol/ mmol creatinine), whereas 11-dehydro TxB2 was significantly reduced (695 +/- 74 versus 95 +/- 10 pmol/mmol creatinine) (p < 0.0001). Elevated levels of iPF2alpha-III (median, 125 pmol/mmol creatinine; range, 110 to 170) in five patients with COPD declined (median, 90 pmol/mmol creatinine; range, 70 to 110) (p < 0.001) as an acute exacerbation in their clinical condition resolved. Increased urinary iPF2alpha-III is consistent with the hypothesis that oxidative stress occurs in COPD. This provides a basis for dose finding and evaluation of antioxidant therapy in the treatment of this disease.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Age Factors
  • Aged
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Antioxidants / administration & dosage
  • Antioxidants / therapeutic use
  • Arachidonic Acids / metabolism
  • Aspirin / therapeutic use
  • Case-Control Studies
  • Creatinine / urine
  • Cross-Sectional Studies
  • Cyclooxygenase Inhibitors / therapeutic use
  • Dinoprost / analogs & derivatives*
  • Dinoprost / urine
  • Female
  • Follow-Up Studies
  • Free Radicals / metabolism
  • Humans
  • Lipid Peroxidation / physiology
  • Lung Diseases, Obstructive / drug therapy
  • Lung Diseases, Obstructive / etiology
  • Lung Diseases, Obstructive / metabolism
  • Lung Diseases, Obstructive / urine*
  • Male
  • Middle Aged
  • Oxidative Stress / physiology*
  • Oxygen / blood
  • Sex Factors
  • Smoking / adverse effects
  • Thromboxane B2 / analogs & derivatives
  • Thromboxane B2 / urine
  • Time Factors

Substances

  • 8,12-iso-isoprostane F2alpha-III
  • Anti-Inflammatory Agents, Non-Steroidal
  • Antioxidants
  • Arachidonic Acids
  • Cyclooxygenase Inhibitors
  • Free Radicals
  • Thromboxane B2
  • 11-dehydro-thromboxane B2
  • Creatinine
  • Dinoprost
  • Aspirin
  • Oxygen