Influence of long-term supplementation with α-linolenic acid on myocardial lipid peroxidation and antioxidative capacity in spontaneously hypertensive rats

The ischaemic vulnerability of the heart of spontaneously hypertensive rats (SHR) is enhanced after feeding an α-linolenic acid (LNA) enriched diet. Because oxygen radical-induced reactions (e.g. lipid peroxidation) are involved in the ischaemic damage, an increased susceptibility of the SHR heart to such damaging reactions might be the reason. As a sign of the enhanced susceptibility to lipid peroxidation of LNA-fed SHR, we found (measured as TBARS) higher plasma and heart lipid peroxide levels (3.84 ± 0.50 μmol/l vs 2.98 ± 0.78 μmol/l and 507 ± 127 nmol/g prot. vs 215 ± 80 nmol/g prot., respectively) after feeding LNA. Using Fe²⁺/Vit. C to induce lipid peroxidation in myocardial tissue homogenates, we demonstrated the enhanced susceptibility to lipid peroxidation of the LNA-fed SHR heart (68 ± 12 nmol/min × g prot. vs 40 ± 8 nmol/min × g prot.) also in vitro. The myocardial enrichment of n-3 polyunsaturated fatty acids (PUFA) resulting in a higher peroxidation index (Pl 227 vs. 170) and the loss in myocardial activities of the antioxidative enzymes (SOD: 76 ± 24 U × 10³/g prot. vs 235 ± 150 U × 10³/g prot.; GSH-Px: 32 ± 5 U/g prot. vs 110 ± 30 U/g prot.) by feeding LNA could be the cause of the increase in myocardial susceptibility to lipid peroxidation of PUFA supplemented SHR.     

A synopsis of the process of lipid peroxidation since the discovery of the essential fatty acids

Eighty years ago, Burr and Burr, introduced for the first time the concept of essential fatty acids. Now is very well known that requirements for polyunsaturated fatty acids PUFAs can not be met by de novo metabolic processes within mammalian tissues. Animals are absolutely dependent on plants for providing the two major precursors of the n-6 and n-3 fatty acids, C18:2n-6; linoleic and C18:3n-3; α-linolenic acids. In animal tissues these precursors are transformed to fatty acids containing three to six double bonds. During the last four decades the interest in polyunsaturated fatty acids has augmented manifolds, and the number of published studies is rising each year. The current impetus for this interest has been mainly the observation that PUFAs and their metabolites have several physiological roles including: energy provision, membrane structure, cell signaling and regulation of gene expression. In addition the observation that PUFAs are targets of lipid peroxidation opens a new important area of investigation. Melatonin, the main secretory product of the pineal gland, efficiently scavenges both the hydroxyl and peroxyl radicals counteracting lipid peroxidation in biological membranes. In addition the two key pineal biochemical functions, lipoxygenation and melatonin synthesis may be synergistically regulated by the status of n-3 essential fatty acids. At the retina level, free radicals may preferentially react with the membrane polyunsaturated fatty acids leading to the release of lipoperoxide radicals. These lipoperoxides can induce oxidative stress linked to membrane lysis, damage to neuronal membranes may be related to alteration of visual function.     

Effects of fatty acids on the growth of Caco-2 cells

Epidemiological studies suggest that polyunsaturated fatty acids may protect against colorectal neoplasia. In order to explore this observation, cell proliferation and viability, lipid composition, membrane fluidity, and lipid peroxidation were measured in Caco-2 cells after 48h incubation with various fatty acids. Saturated and monounsaturated fatty acids incorporated less well in the membranes than polyunsaturated fatty acids (PUFAs). All of the PUFAs tested had an inhibitory effect on cell proliferation/viability whereas the saturated and monounsaturated fatty acids did not. Addition of palmitic acid had no significant effect on membrane fluidity whereas unsaturated fatty acids increased membrane fluidity in a dose-dependent manner. PUFAs strongly increased tumor cell lipid peroxidation in a dose-dependent manner. Saturated and monounsaturated fatty acids increased lipid peroxidation in this cell line only at high concentration. Preincubation of Caco-2 cells with vitamin E prevented the inhibition of proliferation/viability, the elevation of the MDA concentration and the increased membrane fluidity induced by PUFAs. Our data indicate that PUFAs are potent inhibitors of the growth of colon cancer cells in vitro.     

The cold but not hard fats in ectotherms: consequences of lipid restructuring on susceptibility of biological membranes to peroxidation,a review

The production of reactive oxygen species is a regular feature of life in the presence of oxygen. Some reactive oxygen species possess sufficient energy to initiate lipid peroxidation in biological membranes, self-propagating reactions with the potential to damage membranes by altering their physical properties and ultimately their function. Two of the most prominent patterns of lipid restructuring in membranes of ectotherms involve contents of polyunsaturated fatty acids and ratios of the abundant phospholipids, phosphatidylcholine and phosphatidylethanolamine. Since polyunsaturated fatty acids and phosphatidylethanolamine are particularly vulnerable to oxidation, it is likely that higher contents of these lipids at low body temperature elevate the inherent susceptibility of membranes to lipid peroxidation. Although membranes from animals living at low body temperatures may be more prone to oxidation, the generation of reactive oxygen species and lipid peroxidation are sensitive to temperature. These scenarios raise the possibility that membrane susceptibility to lipid peroxidation is conserved at physiological temperatures. Reduced levels of polyunsaturated fatty acids and phosphatidylethanolamine may protect membranes at warm temperatures from deleterious oxidations when rates of reactive oxygen species production and lipid peroxidation are relatively high. At low temperatures, enhanced susceptibility may ensure sufficient lipid peroxidation for cellular processes that require lipid oxidation products.     

Even a Chronic Mild Hyperglycemia Affects Membrane Fluidity and Lipoperoxidation in Placental Mitochondria in Wistar Rats

It is known the deleterious effects of diabetes on embryos, but the effects of diabetes on placenta and its mitochondria are still not well known. In this work we generated a mild hyperglycemia model in female wistar rats by intraperitoneal injection of streptozotocin in 48 hours-old rats. The sexual maturity onset of the female rats was delayed around 6–7 weeks and at 16 weeks-old they were mated, and sacrificed at day 19th of pregnancy. In placental total tissue and isolated mitochondria, the fatty acids composition was analyzed by gas chromatography, and lipoperoxidation was measured by thiobarbituric acid reactive substances. Membrane fluidity in mitochondria was measured with the excimer forming probe dipyrenylpropane and mitochondrial function was measured with a Clark-type electrode. The results show that even a chronic mild hyperglycemia increases lipoperoxidation and decreases mitochondrial function in placenta. Simultaneously, placental fatty acids metabolism in total tissue is modified but in a different way than in placental mitochondria. Whereas the chronic mild hyperglycemia induced a decrease in unsaturated to saturated fatty acids ratio (U/S) in placental total tissue, the ratio increased in placental mitochondria. The measurements of membrane fluidity showed that fluidity of placenta mitochondrial membranes increased with hyperglycemia, showing consistency with the fatty acids composition through the U/S index. The thermotropic characteristics of mitochondrial membranes were changed, showing lower transition temperature and activation energies. All of these data together demonstrate that even a chronic mild hyperglycemia during pregnancy of early reproductive Wistar rats, generates an increment of lipoperoxidation, an increase of placental mitochondrial membrane fluidity apparently derived from changes in fatty acids composition and consequently, mitochondrial malfunction.     

Zn对细胞保护作用机理的研究

应用扫描质子微探针和同步辐射ｘ荧光分析技术测定了细胞中元素的分布和组成,为确定Zn是细胞结构成分提供了直接的实验依据.用上述核技术结合有关生化指标,分析测定了正常和损伤细胞（脂质过氧化损伤）中Fe,Zn和丙二醛、SH基含量变化的相互关系.实验结果表明,当细胞发生脂质过氧化损伤时,Fe含量和丙二醛含量同步增高,而Zn含量和SH基量则降低.给细胞补充Zn后,提高了细胞质膜中的Zn含量,SH基量也随之增加,同时丙二醛量降低.提示Zn保护细胞完整性的作用机理之一是控制脂质过氧化作用.Zn可保护膜蛋白的SH基,减少和阻止被Fe所催化的过氧化反应.     

Lipid peroxidation in pigmented and unpigmented liver tissues: protective role of melanin

The protective role of melanin as an antioxidant biopolymer against lipid peroxidation was investigated. In pigmented frog liver and in albino rat liver the following were tested: thiobarbituric acid (TBA) reactive material (to show the induced lipoperoxidation in vitro), fatty acids, and reduced glutathione content. Our results show that susceptibility to the in vitro lipoperoxidation induced by ferrous ions is lower in the tissue containing melanin, though the content of the polyunsaturated fatty acids is higher in pigmented than in unpigmented tissues and reduced glutathione levels are lower in pigmented tissue. Our data support the hypothesis that melanin could reduce lipoperoxidation in pigmented tissue.     

Changes in fatty acids composition,hydrogen peroxide generation and lipid peroxidation of salt-stressed corn (<Emphasis Type="Italic">Zea mays</Emphasis> L.) roots

Comparative study about the salt-induced oxidative stress and lipid composition has been realised in primary root tissues for two varieties of maize (Zea mays L.) in order to evaluate their responses to salt stress. The root growth, root water content (WC), hydrogen peroxide (H₂O₂) generation, lipid peroxidation, membrane stability index and the changes in the profile of fatty acids composition were investigated. Salinity impacts in term of root growth, water content, H₂O₂ generation, lipid peroxidation and membrane destabilisation were more pronounced in primary roots of Aristo than in those of Arper indicating more sensitivity of the first variety. It was confirmed by gas chromatography that the composition of fatty acids in roots of both varieties was constituted mainly by 16:0 and 18:0 as major saturated fatty acids and 18:1ω9, 18:2ω6 and 18:3ω3 as major unsaturated fatty acids. Total lipid extracts from the roots of both varieties showed that the lipid saturation level increased under salt stress, notwithstanding the increased proportion of polyunsaturated fatty acids. The changes in lipid saturation being predominantly due to decreases in oleic acid (18:1ω9) and increases in palmitic acid (16:0). However, Arper root extracts contained a lower proportion of saturated lipids than Aristo. The enhanced proportion of highly polyunsaturated fatty acids especially linolenic and eicosapentaenoic acids was considered to be the characteristic of the relatively salt tolerance in Arper roots.     

Liver and heart mitochondria obtained from Adelie penguin (Pygoscelis adeliae) offers high resistance to lipid peroxidation

Lipid peroxidation is generally thought to be a major mechanism of cell injury in aerobic organisms subjected to oxidative stress. All cellular membranes are especially vulnerable to oxidation due to their high concentration of polyunsaturated fatty acids. However, birds have special adaptations for preventing membrane damage caused by reactive oxygen species. This study examines fatty acid profiles and susceptibility to lipid peroxidation in liver and heart mitochondria obtained from Adelie penguin (Pygoscelis adeliae). The saturated fatty acids in these organelles represent approximately 40-50% of total fatty acids whereas the polyunsaturated fatty acid composition was highly distinctive, characterized by almost equal amounts of 18:2 n-6; 20:4 n-6 and 22:6 n-3 in liver mitochondria, and a higher proportion of 18:2 n-6 compared to 20:4 n-6 and 22:6 n-3 in heart mitochondria. The concentration of total unsaturated fatty acids of liver and heart mitochondria was approximately 50% and 60%, respectively, with a prevalence of oleic acid C18:1 n9. The rate C20:4 n6/C18:2 n6 and the unsaturation index was similar in liver and heart mitochondria; 104.33 +/- 6.73 and 100.09 +/- 3.07, respectively. Light emission originating from these organelles showed no statistically significant differences and the polyunsaturated fatty acid profiles did not change during the lipid peroxidation process.     

Metabolic rate and membrane fatty acid composition in birds: a comparison between long-living parrots and short-living fowl

Both basal metabolic rate (BMR) and maximum lifespan potential (MLSP) vary with body size in mammals and birds and it has been suggested that these are mediated through size-related variation in membrane fatty acid composition. Whereas the physical properties of membrane fatty acids affect the activity of membrane proteins and, indirectly, an animal’s BMR, it is the susceptibility of those fatty acids to peroxidation which influence MLSP. Although there is a correlation between body size and MLSP, there is considerable MLSP variation independent of body size. For example, among bird families, Galliformes (fowl) are relatively short-living and Psittaciformes (parrots) are unusually long-living, with some parrot species reaching maximum lifespans of more than 100 years. We determined BMR and tissue phospholipid fatty acid composition in seven tissues from three species of parrots with an average MLSP of 27 years and from two species of quails with an average MLSP of 5.5 years. We also characterised mitochondrial phospholipids in two of these tissues. Neither BMR nor membrane susceptibility to peroxidation corresponded with differences in MLSP among the birds we measured. We did find that (1) all birds had lower n-3 polyunsaturated fatty acid content in mitochondrial membranes compared to those of the corresponding tissue, and that (2) irrespective of reliance on flight for locomotion, both pectoral and leg muscle had an almost identical membrane fatty acid composition in all birds.     

Lipid peroxidation and superoxide dismutase activity in relation to photoinhibition induced by chilling in moderate light

The effect of a chilling stress, at a moderate photon flux density for a few hours, on the peroxidation of membrane lipids and on superoxide dismutase (SOD) activity was compared in leaf slices of chilling-sensitive and chilling-insensitive plants. The aim was to determine if susceptibility to chill-temperature photoinhibition could be related to either damage to membrane lipids by superoxide and-or a decrease in activity of chloroplast SOD. Plants used were Nerium oleander L., grown at 45° C, and Cucumis sativus L., both susceptible to chill-temperature photoinhibition, and N. oleander, grown at 20° C and Spinacia oleracea L., both insensitive to chill-temperature photoinhibition. Lipid peroxidation was assessed by measuring the concentration of malondialdehyde (MDA). Leaf slices from all plants showed a basal level of MDA which decreased by about 15% when the leaf slices were chilled in the light. The level of MDA was not increased by the addition of either KHCO₃ or methyl viologen during chilling but it was increased, up to threefold, by the addition of Rose Bengal, which produces singlet oxygen. Chloroplast SOD activity was assessed in leaf extracts as the cyanide-sensitive production of H₂O₂ in a system which produced superoxide. Activity of SOD was similar in all the plants and was altered little by chilling. The results show that for the plants tested, chilling at a moderate photon flux density for 5 h does not increase the susceptibility of cell membranes to peroxidative damage nor does it decrease the activity of SOD. It was concluded that the susceptibility of chilling-sensitive plants to chill-temperature photoinhibition cannot be explained on the basis of differences in the vulnerability of membrane lipids to damage by superoxide or differences in SOD activity.Abbreviations Chl chlorophyll - MDA malondialdehyde - MV methyl viologen - O ₂ ^- superoxide - 20°-oleander Nerium oleander grown at 20° C - 45°-oleander N. oleander grown at 45° C - PFD photon flux density - SOD superoxide dismutase Deceased     

Photodynamic Activity of Compounds Structurally Related to Cercosporin

The photodynamic activity of three compounds structurally related to cercosporin (iso-cercosporin, phleichrome, iso-phleichrome) and rubellin, a pigment possessing an anthra-quinone-like structure, was studied. As previously reported for cercosporin, iso-cercosporin, phleichrome, iso-phleichrome and rubellin, when irradiated by an incandescent lamp, induced oxygen uptake and malondialdehyde (MDA) formation in pea stem and rat liver mitochondria and microsomes. All these compounds were also capable of inhibiting MDA formation induced by the peroxidizing system ascorbate-FeSO₄. Circumstantial evidence suggests that the compounds, as shown for cercosporin, induce a lipoperoxidative degradation of the polyunsaturated fatty acids of cell membranes when irradiated by light, but at the same time, they are able to lower the lipoperoxidation induced by ferrous ions.     

The Relationship Between Lipid Composition of Red Blood Cells and Their Susceptibility to Lipid Peroxidation

Red blood cells from 31 healthy donors were examined for the cholesterol content, the fatty acid composition. and the susceptibility to lipid peroxidation induced by either hydrogen peroxide or phenylhy-drazine. Lipid peroxidation was monitored by the release of pentane and ethane. In addition, plasma fatty acids were measured in order to find out, whether plasma and red cell fatty acids were correlated. In experiments with hydrogen peroxide, a significant positive correlation was found between the proportion of arachidonic acid (C 20:4n – 6; r = 0.57, p < 0.01) and docosahexaenoic acid (C 22:6; - 3; r = +0.71, p < 0.01), and the release of pentane and ethane, respectively. A significant negative correlation was found between the membrane cholesterol content and the pentane release (r -0.44, p< 0.05). In experiments performed with phenylhydrazine, red cell membrane lipid composition did not influence the susceptibility of red cells to lipid peroxidation. A close correlation was found between plasma and red cell fatty acids (palmitic acid, r = +0.46, p < 0.01; linoleic acid, r = +0.41, p < 0.05; arachidonic acid, r = +0.59, p < 0.01; docosahexaenoic acid, r = +0.67, p < 0.01). The results demonstrated that the degree of peroxide-induced oxidation of erythrocyte lipids depends on the content of polyunsaturated fatty acids in the membrane, which on the other hand, is determined by plasma fatty acids. It is suggested that dietary variations may influence the susceptibility of red cells to lipid peroxidation.     

Superoxide dismutase depletion and lipid peroxidation in rat liver microsomal membranes: correlation with liver carcinogenesis

The depletion of superoxide dismutase in the liver of rats held on a copper-deficient diet for 8 weeks induces two profound modifications in microsomal membrane characteristics. These membranes show: (1) a low degree of peroxidation induced in vitro by both endogenous (NADPH and tert-butylhydroperoxide) and exogenous sources (xanthine/xanthine oxidase) of oxygen radicals as revealed by malondialdehyde and diene-conjugate production; (2) a strong decrease of polyunsaturated and an increase of monounsaturated fatty acid content. These alterations are similar to those found in microsomal membranes from fast-growing hepatomas which exhibit a pronounced saturation of fatty acid pattern and lack superoxide dismutase. These observations support the hypothesis that during hepatocarcinogenesis the loss of superoxide dismutase causes an oxidative stress that increases cellular membrane lipid peroxidation, as a consequence of which the cell responds by synthesizing more saturated fatty acids that permanently modify cell membrane structure and properties.     

Relationship between elevated lipid peroxides,vitamin E deficiency and hypertension in preeclampsia

Preeclampsia or pregnancy-induced hypertension is a major cause of both maternal and fetal-neonatal morbidity and mortality. The deficiency of vitamin E can cause accumulation of lipid peroxidation products, which, in turn, can induce vasoconstriction. This study has examined any evidence of increased cellular lipid peroxidation and accumulation of malonydialdehyde (MDA, an end product of lipid peroxidation) in pregnancy-induced hypertension and any relationship between the elevated MDA and lower vitamin E levels with hypertension in pregnant women. EDTA-Blood was collected from pregnant women at the time of delivery. Plasma vitamin E was determined by HPLC; MDA by the thiobarbituric acid-reactivity. Subjects with diastolic blood pressure(DBP) 90 mm Hg were considered hypertensive (HT) and with <90 mm Hg normotensive (NT). Data (Mean±SE) from 49 NT and 11 HT women show that HT has significantly lower vitamin E (22±1 vs 27±1 nmole/ml, p<0.03) and elevated MDA levels (0.56±0.06 vs 0.43±0.02 nmole/ml, p<0.03) compared to NT; the ages and gestational ages of women were similar. Among all women, there was a significant positive relationship between DBP and MDA levels (r=0.27, p<0.05), and a significant negative relationship between vitamin E levels and DBP (–0.36, p<0.005), and a significant negative relationship between MDA and vitamin E levels (r=–0.27, p<0.05). Thus, HT women's plasma has significantly lower E and higher MDA levels, and DBP significantly correlates with the extent of vitamin E deficiency and increased MDA levels. This study suggests a relationship between elevated lipid peroxidation and lower vitamin E levels and hypertension in pregnancy (preeclampsia).     

On the importance of fatty acid composition of membranes for aging

The membrane pacemaker theory of aging is an extension of the oxidative stress theory of aging. It emphasises variation in the fatty acid composition of membranes as an important influence on lipid peroxidation and consequently on the rate of aging and determination of lifespan. The products of lipid peroxidation are reactive molecules and thus potent damagers of other cellular molecules. It is suggested that the feedback effects of these peroxidation products on the oxidative stress experienced by cells is an important part of the aging process. The large variation in the chemical susceptibility of individual fatty acids to peroxidation coupled with the known differences in membrane composition between species can explain the different lifespans of species, especially the difference between mammals and birds as well as the body-size-related variation in lifespan within mammals and birds. Lifespan extension by calorie-restriction can also be explained by changes in membrane fatty acid composition which result in membranes more resistant to peroxidation. It is suggested that lifespan extension by reduced insulin/IGF signalling may also be mediated by changes in membrane fatty acid composition.     

The extreme longevity of Arctica islandica is associated with increased peroxidation resistance in mitochondrial membranes

The deleterious reactive carbonyls released upon oxidation of polyunsaturated fatty acids in biological membranes are believed to foster cellular aging. Comparative studies in mammals and birds have shown that the susceptibility to peroxidation of membrane lipids peroxidation index (PI) is negatively correlated with longevity. Long‐living marine molluscs are increasingly studied as longevity models, and the presence of different types of lipids in the membranes of these organisms raises questions on the existence of a PI–longevity relationship. We address this question by comparing the longest living metazoan species, the mud clam Arctica islandica (maximum reported longevity = 507 year) to four other sympatric bivalve molluscs greatly differing in longevity (28, 37, 92, and 106 year). We contrasted the acyl and alkenyl chain composition of phospholipids from the mitochondrial membranes of these species. The analysis was reproduced in parallel for a mix of other cell membranes to investigate whether a different PI–longevity relationship would be found. The mitochondrial membrane PI was found to have an exponential decrease with increasing longevity among species and is significantly lower for A. islandica. The PI of other cell membranes showed a linear decrease with increasing longevity among species and was also significantly lower for A. islandica. These results clearly demonstrate that the PI also decreases with increasing longevity in marine bivalves and that it decreases faster in the mitochondrial membrane than in other membranes in general. Furthermore, the particularly low PI values for A. islandica can partly explain this species’ extreme longevity.     

Increased n-3 polyunsaturated fatty acid content of red blood cells from fish oil-fed rabbits increases in vitro lipid peroxidation, but decreases hemolysis.

In view of a possible relationship between fish oil, lipid peroxidation, and atherosclerosis, the in vitro lipid peroxidation susceptibility of red blood cells (RBCs) from rabbits on conventional (-FO) and fish oil-enriched diets (+FO) was investigated. The diet caused substantial increases in the RBC concentrations of n-3 polyunsaturated fatty acids (PUFAs), in combination with decreases in the concentration of oleic acid (18:1) and linoleic acid (18:2). Cumene hydroperoxide-induced oxidative stress led to increased overall fatty acid peroxidation in +FO RBCs compared with with -FO RBCs, as quantitated by GLC fatty acid analysis. However, the increased overall susceptibility to lipid peroxidation of +FO RBCs was not reflected in increased peroxidation of every individual fatty acid. This was observed for endogenous arachidonic acid (20:4) as well as, in separate experiments, for exogenously added parinaric acid (PnA). The increased cumene hydroperoxide-induced PUFA oxidation in +FO RBCs was accompanied by a lesser extent of hemolysis. To account for these observations, it is proposed that the increased n-3 PUFA content of +FO RBCs serves as an oxidizable buffer. The present data suggest that oxidation of fatty acids can occur until a critically low level of intact phospholipid in the RBC membrane is reached, after which the membrane destabilizes and hemolysis occurs. At the same time, the PUFA buffer in +FO RBCs could also prevent oxidative damage to specific membrane proteins, which could also help prevent cell lysis.     

Exogenous spermidine alters in different way membrane permeability and lipid peroxidation in water stressed barley leaves

In order to see whether polyamines will modify membrane functioning in the water stressed plants, barley (Hordeum vulgare) seedlings were treated with spermidine (Spd) prior to dehydration and then the stress-evoked changes in membrane permeability (i.e. in electrolyte leakage from leaves) and lipid peroxidation (indicated by modifications of the malondialdehyde (MDA) level, and of the lipoxygenase (LOX) activity) were followed. The Spd treatement lowered injury index in plants subjected to water deficit, although it slightly increased the stress-promoted LOX activity and increased the MDA level in the studied leaves. Presented results confirm that spermidine stabilizes plant membranes under water stress conditions. However, this effect does not seem to be associated with the Spd-induced modifications in the lipid peroxidation activities.     

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

Objectives

Our 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 Methods

Pregnant 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.

Results

Animals 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.

Conclusion

Key constituents of one carbon cycle (folic acid, vitamin B₁₂ and DHA) may play a role in reducing oxidative stress and inflammation in preeclampsia.