Plasma F2-isoprostane class VI isomers at 12–18 weeks of pregnancy are associated with later occurrence of preeclampsia

Abstract

Preeclampsia (PE) has long been associated with early oxidative stress whereas the symptoms occur later in pregnancy. We have hypothesized that the oxidative stress in PE, as characterized by the presence of F 2 -isoprostanes (F 2 -isoPs) isomers in late pregnancy, should already be present in plasma at the first regular visit of the obstetrical follow-up. There are 64 possible isomers of F 2 -isoPs derived from the oxidation of arachidonic acid (AA) but only one of these isomers has been investigated so far in PE, the classical 8-iso-PGF 2α . Here, we have investigated two regioisomers of class III (8-iso-15(R)-PGF 2α and 8-iso-PGF 2α ) and a mix of two isomers of class VI (±)5-iPF 2α -VI in plasma samples collected prospectively at 12-18 weeks from normotensive controls (n=60) and pregnant mothers who developed PE later in pregnancy (n=33). The plasma samples were subjected to alkaline hydrolysis followed by liquid-liquid extraction to extract total F 2 -isoPs for later quantification by HPLC-MS/MS. The F 2 -isoPs were normalized to either plasma volume or polyunsaturated fatty acids (PUFAs) levels measured by GC-FID in plasma phospholipids. Early in pregnancy, only the class VI F 2 -isoPs isomers were found in concentrations significantly higher in women developing PE later in pregnancy (+ 13%; p=0.0074). Normalisation of F 2 -isoPs to their substrate, AA, or the omega-3 to omega-6 ratio improved the predictability of PE as determined by receiver operating characteristic (from area under the curve of 0.67 to 0.68 and 0.70 respectively). Interestingly, omega-3 fatty acids were 25% higher in the control group than the PE group (P = 0.0225). Total omega-6 PUFAs correlated to F 2 -Isop isomers only in cases of PE (r >

Hydroxychloroquine Mitigates the Production of 8-Isoprostane and Improves Vascular Dysfunction: Implications for Treating Preeclampsia

“…Lupus shares this feature as the key mechanism underlying hypertension, renal dysfunction, and other organ injury [29]. Indeed, the endothelial dysfunction in both preeclampsia and lupus have also been shown to be due, at least in part, to excessive oxidative stress secondary to NOX activation [12,30,31]. Recently, in murine models of lupus, hydroxychloroquine was shown to reverse endothelial dysfunction via the downregulation of NOX, and subsequently, oxidative stress [24,32].…”

Classifying oxidative stress by F2-isoprostane levels across human diseases: A meta-analysis

“…The number in the affected and control groups represents the number of people tested. Data for this figure was extracted from references [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47], [48], [49], [50], [51], [52], [53], [54], [55], [56], [57], [58], [59], [60], [61], [62], [63], [64], [65], [66], [67], [68], [69], [70], [71], [72], [73], [74], [75], [76], [77], [78], [79], [80], [81], [82], [83], [84], [85], [86], [87], [88], [89], [90], [91], [92], [93], [94], [95], [96], [97], [98], [99], [100], [101], [102], [103], [104], [105], [106], [107], [108], [109], [110], [111], [112], [113], [114], [115], [116], [117], [118], …”

Hydroxychloroquine prophylaxis for preeclampsia, hypertension and prematurity in pregnant patients with systemic lupus erythematosus: A meta-analysis

“…26 This endothelial dysfunction may be due to excessive oxidative stress that occurs secondary to nicotinamide adenine dinucleotide phosphate oxidase (NOX) activation. 27–29 Recently, a study using a mouse model has shown that HCQ can protect against oxidative stress-induced endothelial dysfunction and thereby improve renal function inhibiting NOX activity in SLE. 30,31 In vitro studies have shown that HCQ mitigated TNF-α-induced human umbilical vein endothelial cell production of 8-isoprostane and NOX expression.…”