Association of Midgestational Paraoxonase 1 Activity with Pregnancies Complicated by Preeclampsia

ABSTRACT

The antioxidant enzyme paraoxonase 1 is a marker of oxidative stress and has been implicated in the pathogenesis of preeclampsia. Our objective was to determine if an association exists between low paraoxonase 1 activity at midgestation and the development of preeclampsia. We conducted a case-control study of 50 women with preeclampsia and 101 women with uncomplicated term deliveries. Maternal serum collected at 15 to 20 weeks was used to measure paraoxonase 1 activity using two substrates: paraoxon and phenylacetate (arylesterase activity). The groups did not differ with respect to maternal demographics. Paraoxonase 1 activity (paraoxon) was significantly higher in women with preeclampsia compared with controls (19.4 ± 9.4 versus 15.6 ± 8.0 change in absorbance per minute (dA/min), p = 0.009). When stratified by disease severity, paraoxonase 1 activity (paraoxon) was highest in women with severe preeclampsia (21.6 ± 9.1 versus 15.6 ± 8.0 dA/min, p = 0.002). We observed a trend toward higher arylesterase activity in women with preeclampsia compared with controls (0.343 ± 0.07 versus 0.323 ± 0.06 dA/min, p = 0.06). Midgestational paraoxonase 1 activity is higher in women with preeclampsia before clinical signs of the disease are present. Prospective studies are needed to determine the significance of paraoxonase 1 in the pathogenesis of preeclampsia.

KEYWORDS

Lipid dysfunction - oxidative stress - paraoxonase - preeclampsia

REFERENCES

• 1 Saftlas A F, Olson D R, Franks A L, Atrash H K, Pokras R. Epidemiology of preeclampsia and eclampsia in the United States, 1979–1986.  Am J Obstet Gynecol. 1990;  163 460-465
• 2 Centers for Disease Control and Prevention (CDC) . Maternal mortality—United States, 1982–1996.  MMWR Morb Mortal Wkly Rep. 1998;  47 705-707
• 3 Sibai B M, Gordon T, Thom E The National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units et al. Risk factors for preeclampsia in healthy nulliparous women: a prospective multicenter study.  Am J Obstet Gynecol. 1995;  172(2 Pt 1) 642-648
• 4 Dekker G, Kraayenbrink A. Oxygen free radicals in preeclampsia.  Am J Obstet Gynecol. 1991;  164 273-278
• 5 Uotila J T, Tuimala R J, Aarnio T M, Pyykkö K A, Ahotupa M O. Findings on lipid peroxidation and antioxidant function in hypertensive complications of pregnancy.  Br J Obstet Gynaecol. 1993;  100 270-276
• 6 Akyol D, Mungan T, Görkemli H, Nuhoglu G. Maternal levels of vitamin E in normal and preeclamptic pregnancy.  Arch Gynecol Obstet. 2000;  263 151-155
• 7 Sağol S, Ozkinay E, Ozşener S. Impaired antioxidant activity in women with pre-eclampsia.  Int J Gynaecol Obstet. 1999;  64 121-127
• 8 Kharb S. Total free radical trapping antioxidant potential in pre-eclampsia.  Int J Gynaecol Obstet. 2000;  69 23-26
• 9 Madazli R, Benian A, Aydin S, Uzun H, Tolun N. The plasma and placental levels of malondialdehyde, glutathione and superoxide dismutase in pre-eclampsia.  J Obstet Gynaecol. 2002;  22 477-480
• 10 Knapen M F, Mulder T P, Van Rooij I A, Peters W H, Steegers E A. Low whole blood glutathione levels in pregnancies complicated by preeclampsia or the hemolysis, elevated liver enzymes, low platelets syndrome.  Obstet Gynecol. 1998;  92 1012-1015
• 11 Smith G C, Pell J P, Walsh D. Pregnancy complications and maternal risk of ischaemic heart disease: a retrospective cohort study of 129,290 births.  Lancet. 2001;  357 2002-2006
• 12 Irgens H U, Reisaeter L, Irgens L M, Lie R T. Long term mortality of mothers and fathers after pre-eclampsia: population based cohort study.  BMJ. 2001;  323 1213-1217
• 13 Katabuchi H, Yih S, Ohba T et al.. Characterization of macrophages in the decidual atherotic spiral artery with special reference to the cytology of foam cells.  Med Electron Microsc. 2003;  36 253-262
• 14 Costa L G, Vitalone A, Cole T B, Furlong C E. Modulation of paraoxonase (PON1) activity.  Biochem Pharmacol. 2005;  69 541-550
• 15 Deakin S, Leviev I, Guernier S, James R W. Simvastatin modulates expression of the PON1 gene and increases serum paraoxonase: a role for sterol regulatory element-binding protein-2.  Arterioscler Thromb Vasc Biol. 2003;  23 2083-2089
• 16 Durrington P N, Mackness B, Mackness M I. Paraoxonase and atherosclerosis.  Arterioscler Thromb Vasc Biol. 2001;  21 473-480
• 17 Mackness B, Durrington P, McElduff P et al.. Low paraoxonase activity predicts coronary events in the Caerphilly Prospective Study.  Circulation. 2003;  107 2775-2779
• 18 Mackness M I, Harty D, Bhatnagar D et al.. Serum paraoxonase activity in familial hypercholesterolaemia and insulin-dependent diabetes mellitus.  Atherosclerosis. 1991;  86 193-199
• 19 Mackness B, Mackness M I, Arrol S et al.. Serum paraoxonase (PON1) 55 and 192 polymorphism and paraoxonase activity and concentration in non-insulin dependent diabetes mellitus.  Atherosclerosis. 1998;  139 341-349
• 20 Dantoine T F, Debord J, Charmes J P et al.. Decrease of serum paraoxonase activity in chronic renal failure.  J Am Soc Nephrol. 1998;  9 2082-2088
• 21 ACOG Committee on Practice Bulletins--Obstetrics . ACOG practice bulletin. Diagnosis and management of preeclampsia and eclampsia. Number 33, January 2002.  Obstet Gynecol. 2002;  99 159-167
• 22 Gan K N, Smolen A, Eckerson H W, La Du B N. Purification of human serum paraoxonase/arylesterase. Evidence for one esterase catalyzing both activities.  Drug Metab Dispos. 1991;  19 100-106
• 23 Kumru S, Aydin S, Gursu M F, Ozcan Z. Changes of serum paraoxonase (an HDL-cholesterol-associated lipophilic antioxidant) and arylesterase activities in severe preeclamptic women.  Eur J Obstet Gynecol Reprod Biol. 2004;  114 177-181
• 24 Uzun H, Benian A, Madazli R, Topçuoğlu M A, Aydin S, Albayrak M. Circulating oxidized low-density lipoprotein and paraoxonase activity in preeclampsia.  Gynecol Obstet Invest. 2005;  60 195-200
• 25 Sarandöl E, Safak O, Dirican M, Uncu G. Oxidizability of apolipoprotein B-containing lipoproteins and serum paraoxonase/arylesterase activities in preeclampsia.  Clin Biochem. 2004;  37 990-996