A Combined Supplementation of Omega-3 Fatty Acids and Micronutrients (Folic Acid, Vitamin B12) Reduces Oxidative Stress Markers in a Rat Model of Pregnancy Induced Hypertension

Abstract

ObjectivesOur earlier studies have highlighted that an altered one carbon metabolism (vitamin B12, folic acid, and docosahexaenoic acid) is associated with preeclampsia. Preeclampsia is also known to be associated with oxidative stress and inflammation. The current study examines whether maternal folic acid, vitamin B12 and omega-3 fatty acid supplementation given either individually or in combination can ameliorate the oxidative stress markers in a rat model of pregnancy induced hypertension (PIH).Materials and MethodsPregnant Wistar rats were assigned to control and five treatment groups: PIH; PIH + vitamin B12; PIH + folic acid; PIH + Omega-3 fatty acids and PIH + combined micronutrient supplementation (vitamin B12 + folic acid + omega-3 fatty acids). L-Nitroarginine methylester (L-NAME; 50 mg/kg body weight/day) was used to induce hypertension during pregnancy. Blood Pressure (BP) was recorded during pregnancy and dams were dissected at d20 of gestation.ResultsAnimals from the PIH group demonstrated higher (p<0.01 for both) systolic and diastolic BP; lower (p<0.01) pup weight; higher dam plasma homocysteine (p<0.05) and dam and offspring malondialdehyde (MDA) (p<0.01), lower (p<0.05) placental and offspring liver DHA and higher (p<0.01) tumor necrosis factor–alpha (TNF–ά) levels as compared to control. Individual micronutrient supplementation did not offer much benefit. In contrast, combined supplementation lowered systolic BP, homocysteine, MDA and placental TNF-ά levels in dams and liver MDA and protein carbonyl in the offspring as compared to PIH group.ConclusionKey constituents of one carbon cycle (folic acid, vitamin B12 and DHA) may play a role in reducing oxidative stress and inflammation in preeclampsia.

Vitamin D restores angiogenic balance and decreases tumor necrosis factor‐α in a rat model of pre‐eclampsia

“…Commonly, the term ‘animal model of PE’ refers to the induction of PE‐like syndrome in rats by treatment with nitric oxide synthase inhibitor NG‐nitro‐ l ‐arginine methylester (L‐NAME) from day 14 of gestation . In this study, we induced hypertension in pregnant rats using L‐NAME.…”

“…Protein carbonyl was measured according to a previous report . Briefly, 0.5 mL extracted protein samples were mixed with an equal volume of 2,4‐dinitrophenylhydrazine (10 mmol/L) in hydrochloride solution (2.5 mol/L) followed by 1‐h incubation at room temperature.…”

Matrix Metalloproteinases in Normal Pregnancy and Preeclampsia

“…In mid- to late pregnant rats, NOS blockade with N ω -nitro-L-arginine methyl ester (L-NAME) causes some of the changes observed in preeclampsia including increases in blood pressure and renal vasoconstriction, proteinuria, thrombocytopenia and IUGR, 23,158,283 supporting that NO production is increased during gestation. Similar to the observation in humans, measurements of NO production in hypertensive pregnant animals have not been consistent.…”

Mechanisms of Endothelial Dysfunction in Hypertensive Pregnancy and Preeclampsia

“…In pregnant rats during mid to late gestation NOS blockade with N ω -nitro-L-arginine methyl ester (L-NAME) causes some of the changes observed in human PE including increases in BP and renal vasoconstriction, proteinuria, thrombocytopenia and IUGR (Khalil et al, 1998; Ramesar et al, 2011; Kemse et al, 2014), supporting a role of increased NO production during gestation. Similar to the observation in humans, measurements of NO production in HTN-Preg animals have not produced consistent results.…”