|Year : 2021 | Volume
| Issue : 2 | Page : 110-116
Antioxidant and malondialdehyde status in preeclampsia
Ejuoghamran Oriseseyigbemi Onovughakpo-Sakpa1, Chukwu E Onyeneke2, Ekiye Ayinbuomwan1, Kenneth Atoe3
1 Department of Chemical Pathology, University of Benin, Benin City, Nigeria
2 Department of Biochemistry, University of Benin, Benin City, Nigeria
3 Department of Clinical Pathology, Edo University, Iyamho, Edo State, Nigeria
|Date of Submission||20-Mar-2021|
|Date of Decision||16-May-2021|
|Date of Acceptance||16-May-2021|
|Date of Web Publication||10-Aug-2021|
Dr. Ejuoghamran Oriseseyigbemi Onovughakpo-Sakpa
Department of Chemical Pathology, University of Benin, Benin City, Edo State
Source of Support: None, Conflict of Interest: None
Context: Preeclampsia is a multisystem disorder, although the cause is unknown, yet oxidative stress is a prominent feature; therefore, assessment of oxidative stress indices in preeclamptics would no doubt improve their clinical outcome. Aim: The aim of this study was to determine the antioxidant and malondialdehyde (MDA) status in preeclampsia. Setting and Design: This was a cross-sectional descriptive study. Subjects and Methods: One hundred and ninety-six (196) respondents consisting of 124 preeclampsia (PE), 36 normotensive pregnant women (NPW), and 36 analbuminuric hypertensive pregnant women (AHPW) participated in this study. Blood samples were collected for estimation of plasma uric acid, serum MDA, nitric oxide (NO), superoxide dismutase (SOD), glutathione peroxidase (GPX), glutathione reductase (GSSH) and catalase (CAT) activities, Vitamin C (Vit C), and Vitamin E (Vit E) using standard methods. Statistical Analysis Used: The Statistical Package for the Social Sciences version 16 with level of significance set at P < 0.05 was used for statistical analysis. Results: Plasma uric acid level was significantly higher (P < 0.05) in PE than in AHPW and NPW. MDA levels, SOD, CAT, and GPX activities showed a significant increase (P < 0.05) in PE and AHPW when compared to NPW, while GSSH, NO, Vit C, and Vit E levels were significantly higher (P < 0.05) in NPW than in PE and AHPW. Most oxidative stress indicators were higher in PE and AHPW than in NPW in the 2nd and 3rd trimesters, while Vit C and E were lower. Plasma uric acid, MDA and NO levels, SOD, and GPX activities were significantly higher (P < 0.05) in severe than in mild PE. Conclusion: from our findings, it can be safely suggested that oxidative stress is related to the severity of preeclampsia.
Keywords: Antioxidant status, nitric oxide, plasma uric acid, preeclampsia
|How to cite this article:|
Onovughakpo-Sakpa EO, Onyeneke CE, Ayinbuomwan E, Atoe K. Antioxidant and malondialdehyde status in preeclampsia. Niger J Exp Clin Biosci 2021;9:110-6
|How to cite this URL:|
Onovughakpo-Sakpa EO, Onyeneke CE, Ayinbuomwan E, Atoe K. Antioxidant and malondialdehyde status in preeclampsia. Niger J Exp Clin Biosci [serial online] 2021 [cited 2022 Aug 14];9:110-6. Available from: https://www.njecbonline.org/text.asp?2021/9/2/110/323674
| Introduction|| |
Preeclampsia (PE) is a multisystem disorder of unknown etiology characterized by the development of hypertension to the extent of 140/90 mmHg or more with proteinuria after 20 weeks of pregnancy in a previously normotensive and nonproteinuric woman.
It occurs only in the presence of the placenta even when there is no fetus (as in hydatidiform mole) and remits dramatically postpartum, but preeclampsia may also occur in the immediate postpartum period.
Preeclampsia affects approximately 5%–8% of all pregnancies worldwide, and it is one of the leading causes of maternal and perinatal morbidity and mortality worldwide. Nearly one-tenth of all maternal deaths in Africa and Asia and one-quarter in Latin America are associated with hypertensive diseases in pregnancy, a category that encompasses preeclampsia. Although the cause of PE remains largely unknown, the occurrence of oxidative stress is a feature of maternal syndrome. Due to metabolic changes and low-grade inflammation, pregnancy is a condition of increased susceptibility to oxidative stress. Several organs in pregnancy show increased basal oxygen consumption and changes in substrate/energy use resulting in increased mitochondrial mass and production of reactive oxygen species (ROS).
The main source of ROS initiating the pathophysiological events appears to be the placenta. Abnormal vascular development of the blood vessels in the preeclamptic placenta leads to reduced placental perfusion and induction of hypoxia which by itself is a potent stimulus for ROS formation.
Malondialdehyde (MDA) serves as a potential biomarker of oxidative damage and disease severity. In preeclamptic women, MDA level correlates with the severity of the disease and is a good indicator of lipid peroxidation and oxidative stress levels.
Uric acid is the major end product of purine metabolism. Preeclampsia, which is characterized by trophoblastic tissue shedding, widespread endothelial dysfunction, and inflammation, might be propagated by uric acid.
In this study, we intend to determine the antioxidant and MDA status in preeclampsia as well as to assess uric acid status and some indices of oxidative stress in preeclamptic patients.
| Subjects and Methods|| |
The subjects were registered preeclamptic antenatal care patients of the Obstetrics and Gynecology Department of Government Specialist Hospital, Benin City, Edo State, Nigeria. The control subjects were normotensive pregnant women (NPW) and analbuminuric hypertensive pregnant women (AHPW) of the same department and within the same age range. Patients were considered hypertensive when blood pressure (BP) >140/90 mmHg.
Sample size was 196 (calculated from the Cochran's formulae). Before carrying out the study, ethical clearance was obtained from the Research and Ethics Committee of the Ministry of Health, Benin City, Edo Sate, Nigeria. Consent was obtained from all participants. Structured questionnaires were administered to the study groups and used to document their personal data, medical history, social, obstetric, and family history. A physical medical examination was carried out to measure their BPs.
Fresh urine samples were collected into sterile bottles in the hospital under supervision. The urine was used for the determination of urine albumin (protein) and creatinine. Blood samples were also collected from the antecubital veins following routine aseptic procedure using a 10 ml syringe and dispensed into different specimen bottles containing lithium heparin for uric acid estimation and plain tubes for superoxide dismutase (SOD), glutathione peroxidase (GPX), glutathione reductase (GSSH), MDA, NO, and catalase (CAT). Both samples were centrifuged at 3000 revs/min after allowing the sample in the plain tubes to stand for 30 min to clot. The plasma and serum were harvested with clean Pasteur pipette and stored at 2–8°C and analyzed within 48 h.
The uricase/horseradish peroxidase direct colorimetric method was used in the analysis of uric acid. MDA was determined according to the method of Armstrong and Browne. GPX and GSSH were analyzed according to the procedure described by Paglia and Valentine. Ultraviolet spectrophotometry based on the measurement of hydrogen peroxide substrate was used to analyze CAT. Nitric oxide (NO) was determined using the diazotization method. The ferric-reducing/antioxidant ascorbic acid method was used in the assay of Vitamin C (Vit C). Tsen's modification of Emmerie–Engel method was used to assay for Vitamin E (Vit E), and the spectrophotometric method described by Ukeda et al. was used in the analysis of SOD.
Data were collected and entered into a pro forma and analyzed using the Statistical Package for the Social Sciences (SPSS) version 16.0 (SPSS Inc. Chicago, IL, U.S.A). Comparisons of means between the groups were done using the Student's t-test. Pearson's correlation was used in calculating the correlations between any two variables. Univariate analyses were presented as frequencies, while bivariate or multivariate analyses were presented as means ± standard error of mean. The level of statistical significance was set at P < 0.05 for all tests. Data presentation, tables, and charts were done using Microsoft Office.
| Results|| |
At the conclusion of the study, a total of 196 respondents participated, comprising 124 preeclampsia (PE), 36 NPW, and 36 analbuminuric hypertensive pregnant women (AHPW).
Most of the PE (44%) and NPW (41.7%) were in the age range of 31–35 years, while most of the AHPW (41.7%) were in the age range of 36–40 years.
Among the PE, 39 (31.5%) were mild, while 85 (68.5%) had severe preeclampsia (PE) based on a BP of >160/110 mmHg [Figure 1].
|Figure 1: Severity of preeclampsia. Values in parenthesis represent percentage distribution|
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Results obtained showed significantly increased (P < 0.05) MDA level, SOD, CAT, and GPX activities in PE (76.34 ± 3.54 mg/ml, 366.01 ± 15.03 IU/ml, 12.44 ± 0.29 IU/ml, and 272.91 ± 6.99 IU/ml, respectively) and AHPW (57.33 ± 7.93 mg/ml, 262.11 ± 12.42 IU/ml, 10.42 ± 1.72 IU/ml, and 251.04 ± 6.55 IU/ml, respectively) when compared to NPW (30.61 ± 3.23 mg/ml, 163.91 ± 12.41 IU/ml, 10.51 ± 0.74 IU/ml, and 144.19 ± 6.08 IU/ml, respectively). Furthermore, MDA levels, SOD, and GPX activities were significantly higher (P < 0.05) in PE than in AHPW while the increase in SOD in PE was not significant (P > 0.05) when compared with AHPW. However, GSSH activity was significantly higher (P < 0.05) in NPW (56.99 ± 18.23 IU/ml) than in PE (38.75 ± 2.96 IU/ml) and AHPW (29.36 ± 3.33 IU/ml) and also in PE when compared to AHPW. NO was significantly higher (P < 0.05) in PE (261.98 ± 11.27 μM/ml) and AHPW (248.38 ± 51.23 μM/ml) than in NPW (196.20 ± 22.18 μM/ml). The mean serum Vit C level was significantly higher (P < 0.05) in NPW (17.24 ± 0.77 mg/ml) than in AHPW (12.85 ± 1.11 mg/ml) and PE subjects (8.43 ± 1.23 mg/ml) while Vit E level was significantly higher (P < 0.05) in NPW (2.22 ± 0.38 mg/ml) and AHPW (2.10 ± 0.11 mg/ml) than in PE (0.80 ± 0.09 mg/ml). Plasma uric acid value was significantly higher (P < 0.05) in PE (6.90 ± 0.11 mg/dl) subjects when compared to AHPW (4.13 ± 0.62 mg/dl) or NPW (3.75 ± 0.19 mg/dl) [Table 1].
|Table 1: Plasma uric acid, malondialdehyde, molecular, and antioxidant enzymes in preeclamptics, normotensive pregnant women, and analbuminuric hypertensive pregnant women subjects|
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Serum MDA was significantly higher (P < 0.05) in PE (77.96 ± 4.77 mg/ml) and AHPW (76.6 ± 0.89 mg/ml) than in NPW (30.83 ± 3.06 mg/ml) in the 2nd trimester, while in the 3rd trimester, it was significantly higher (P < 0.05) in PE (74.74 ± 5.42 mg/ml) than in AHPW (61.92 ± 2.90 mg/ml) and NPW (36.40 ± 5.31 mg/ml). The activity of SOD was significantly higher (P < 0.05) in the 2nd and 3rd trimesters in the PE (267.29 ± 13.36 IU/ml and 404.74 ± 10.68 IU/ml, respectively) than in AHPW (207.56 ± 11.04 IU/ml and 320.27 ± 10.59 IU/ml, respectively) and NPW (153. 64 ± 11.33 IU/ml and 188.90 ± 9.10 IU/ml, respectively). Serum CAT activity was higher in the 2nd trimester than the 3rd trimester in all the study groups. Furthermore, in the 3rd trimester, serum CAT was significantly higher (P < 0.05) in NPW (10.23 ± 0.81 IU/ml) than in PE (7.73 ± 0.58 IU/ml) and nonsignificantly higher than in AHPW (8.91 ± 0.66 IU/ml). GPX level was higher in the 2nd trimester than in the 3rd trimester in all the groups and was significantly higher (P < 0.05) in the 2nd and 3rd trimesters in PE (291.90 ± 4.40 IU/ml and 253.93 ± 1.61 IU/ml, respectively) than in AHPW (201.74 ± 3.70 IU/ml and 190.34 ± 6.02 IU/ml, respectively) and NPW (155.14 ± 6.08 IU/ml and 135.43 ± 3.11 IU/ml, respectively). Higher activities of GSSH were also observed in the 2nd trimester than in the 3rd trimester across all the groups. GSSH was significantly higher (P < 0.05) in PE (59.48 ± 3.75 IU/ml and 33.80 ± 1.58 IU/ml, respectively) and AHPW (34.91 ± 1.10 IU/ml and 23.60 ± 0.30 IU/ml, respectively) than in the NPW (16.23 ± 3.30 IU/ml and 12.51 ± 5.30 IU/ml, respectively) and also significantly higher (P < 0.05) in PE than in AHPW in the 3rd trimester. NO levels were significantly higher (P < 0.05) in PE (244.01 ± 5.16 μM/ml) and AHPW (235.46 ± 6.42 μM/ml) than in NPW (208.04 ± 10.31 μM/ml) in the 2nd trimester, while in the 3rd trimester, NO levels were significantly higher (P < 0.05) in PE (288.50 ± 7.70 μM/ml) than in NPW (186.74 ± 7.11 μM/ml) and AHPW (252.76 ± 5.64 μM/ml). Mean Vit C levels were significantly lower (P < 0.05) in the 2nd and 3rd trimesters in PE (7.46 ± 1.32 mg/ml and 9.17 ± 0.85 mg/ml, respectively) and AHPW (12.70 ± 0.36 mg/ml and 13.16 ± 0.39 mg/ml, respectively) than in NPW (17.78 ± 1.32 mg/ml and 16.71 ± 1.78 mg/ml, respectively). There were higher levels of Vit E in the PE and NPW in the 2nd trimester than in the 3rd trimester while among AHPW Vit E was higher in the 3rd trimester than in the 2nd trimester. Serum Vit E, however, was higher (P < 0.05) in the 2nd and 3rd trimesters in NPW (3.41 ± 0.89 mg/ml and 2.76 ± 0.29 mg/ml, respectively) than in AHPW (2.84 ± 0.21 mg/ml and 0.97 ± 0.10 mg/ml, respectively) and PE (1.11 ± 0.05 mg/ml and 0.71 ± 1.11 mg/ml, respectively). Plasma uric acid level was significantly higher (P < 0.05) in the 2nd and 3rd trimesters in PE (5.29 ± 0.17 mg/dl and 7.13 ± 0.16 mg/dl, respectively) than in NPW (3.59 ± 0.31 mg/dl and 4.46 ± 0.27 mg/dl, respectively) and AHPW (4.20 ± 0.32 mg/dl and 5.28 ± 0.21 mg/dl, respectively) [Table 2].
|Table 2: Plasma uric acid, malondialdehyde, molecular, and antioxidant status in preeclamptics, normotensive pregnant women, and analbuminuric hypertensive pregnant women in the various trimesters|
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MDA and NO levels, SOD, GPX activities, and plasma uric acid levels were significantly higher (P < 0.05) in severe PE (81.04 ± 4.44 mg/ml, 286.97 ± 28.35 μM/ml, 402.75 ± 38.67 IU/ml, 79.66 ± 8.39 IU/ml, and 6.93 ± 0.13 mg/dl, respectively) than in mild PE (70.79 ± 5.97 mg/ml, 245.11 ± 10.25 μM/ml, 292.04 ± 29.73 IU/ml, 61.87 ± 13.07 IU/ml, and 4.96 ± 0.23 mg/dl, respectively). CAT and GSSH activities and Vit C levels were nonsignificantly higher (P > 0.05) in severe PE (12.72 ± 0.34 IU/ml, 39.57 ± 3.71 IU/ml, and 17.81 ± 0.91 mg/ml, respectively) than in mild PE (11.87 ± 0.58 IU/ml, 37.74 ± 4.9 IU/ml, and 16.07 ± 1.49 mg/ml, respectively), while Vit E was significantly higher (P < 0.05) in mild PE (2.59 ± 0.20 mg/ml) than in severe PE (1.88 ± 0.12 mg/ml) [Table 3].
|Table 3: Plasma uric acid, malondialdehyde, molecular, and antioxidant enzymes in preeclamptics subjects based on severity|
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| Discussion|| |
In Nigeria, preeclampsia has a prevalence rate of 5.6%, and it is associated with significant maternal and fetal mortality worldwide. This calls for the need to detect metabolic changes early in preeclampsia in order to improve maternal and fetal outcome.
MDA is the product of the reaction of free radicals with polyunsaturated membrane lipids, and it is used as an index of free radical injury. Serum MDA levels were higher in PE and AHPW than in NPW. In this study, higher serum MDA levels in severe PE were observed than in mild PE. A similar report has been given by Sharma et al. in their study on normal pregnancy and preeclampsia in New Delhi, India. Our results suggest that lipid peroxidation is related to the severity of preeclampsia. Many studies have shown increased MDA levels in serum, plasma, and placental tissue of preeclamptic women. Studies have also shown increased placental and decidua levels of the antioxidant enzymes GSSH and GPX in patients with severe preeclampsia., The activities of oxidative stress enzyme markers SOD, CAT, and GPX were also higher in severe than mild preeclampsia, as has been earlier reported by Sharma et al. This study also showed a higher level of NO in severe than in mild preeclampsia. This indicates that the increase is directly related to the severity of the disorder. This study also observed a higher level of Vit C and Vit E in mild than in severe preeclampsia. A similar report was also given in studies done by Sharma et al. This could be because the pathological burden of the disorder may have overwhelmed the availability of these antioxidants.
In this study, higher plasma levels of MDA were observed in the third trimester of the preeclamptic group. A similar report has been given by Atiba and Oghagbon et al. in their studies on preeclamptic women in South West Nigeria and NPW in South–South Nigeria., This finding is attributed to disease burden as evidenced by lower BP and urinary protein in the 3rd trimester. Vascularized endothelial damage that results from free radical generation and possibly preeclampsia may have started from 20 weeks of pregnancy and may worsen with increasing demand for oxygen from maternal circulation by the growing placenta. An increase in SOD activity was also observed which is similar to that obtained by Oghagbon et al., and this increase was significant in the preeclamptic group. They suggested that SOD could be the major antioxidant defense against oxidative stress in pregnancy. Decreased activities in serum CAT, GPX, and GSSH were observed in the third trimester for PE, NPW, and AHPW. The decrease in CAT and GSSH was more significant in the NPW and AHPW than in the preeclamptic group, while decreased serum level of GPX was more significant in the preeclamptic group. Oghagbon et al. in their study on normal pregnancy also reported decreased activities in CAT and GSSH from first to third trimester which could be due to the oxidative burden arising from increased production of lipid peroxides.
Oxidative stress may cause endothelial dysfunction which may lead to hypertension by reduced release of vasodilating agents such as NO which is thought to have a major effect on gestational vasodilation. There was a decrease in serum NO level in the third trimester of the PE, NPW, and AHPW compared to the second trimester. However, the levels were higher in the PE and AHPW than in the NPW.
Vit C is an antioxidant and can also be referred to as a reducing agent which reacts with superoxide and other lipid peroxide radicals, while Vit E, also an antioxidant, is a chain terminator. Vit E protects polyunsaturated fatty acid from peroxidative damage by donating hydrogen to the lipid peroxyl radical. In this study, serum levels of Vit C and Vit E were higher in NPW than in PE and AHPW in the second and third trimesters possibly due to the overwhelming effect of the pathological burden of preeclampsia. It was also observed that serum Vit C was significantly higher and Vit E significantly lower in the third trimester in all the study groups. Atiba had reported higher Vit C and E levels in normal pregnancy than in preeclamptic pregnant women but nonsignificant changes between the second trimester and the third trimester.. However, Luqman et al. and Hassan and Onu observed decreasing levels of Vit C as pregnancy progressed in North Central Nigerian subjects.,
In this study, a significant elevation in plasma uric acid was observed in PE than in the NPW and AHPW. This agrees with the earlier study of Vyakaranam et al. Egwuatu in his studies on Nigerian primigravidae with preeclampsia and Wakwe and Abudu in their study on pregnancy-induced hypertension in Nigerian women found significant elevations in serum uric acid levels in preeclampsia. According to Bainbridge and Roberts, hyperuricemia in PE is multifactorial and could be due to decreased renal excretion and also increased oxidative stress resulting from placental ischemia (hypoxia) and xanthine oxidase activity. Plasma uric acid was also found to be significantly higher in AHPW than in NPW. This finding agrees with the earlier study of Hawkins. In our study, plasma uric acid was found to be higher in the third than in the second trimester in NPW, AHPW, and PE. Dinesh reported that uric acid has antioxidant properties that serve to protect from oxidative stress, but it also appears to contribute directly to endothelial dysfunction by its pro-inflammatory effects as well as to hypertension during preeclampsia. Our study showed a significantly higher uric acid level in severe than in mild preeclampsia which is corroborated by studies of Voto, who studied preeclamptics in Argentina and Lim et al. on hypertensive disease of pregnancy in India., Bargale et al. in their study on preeclamptics in Karnataka, India, also found an increase in serum uric acid in severe than in mild preeclampsia. According to Roberts, plasma uric acid estimation is as important as proteinuria in identifying the risk of renal involvement and fetal compromise, and it has also been found to be a stress predictor of maternal disease progression and fetal outcome. It could, therefore, be useful as an inexpensive marker for predicting disease severity, renal function status, and fetal growth retardation in women with hypertensive disease in pregnancy.
Salako in their study on hypertensive disorders of pregnancy in South West Nigeria (Ibadan) found normal serum uric acid. However, their study was on primigravidae in their 1st trimester. Egwuatu in his study on Nigerian primigravidae with preeclampsia predicted that the changes in serum uric acid can prominently be correlated with the degree of proteinuria than the level of hypertension.
| Conclusion|| |
Oxidative stress is the presence of ROS in excess of antioxidants' buffering capacity. We observed in this study a significant increase in the levels of oxidative stress markers (MDA, SOD, CAT, and GPX) in PE than in NPW and AHPW and also in severe than in mild PE. Serum NO was higher in PE than in AHPW and NPW. There was also a statistically lower level of Vit C and Vit E in the PE, while the levels of these vitamins were higher in mild than in severe PE. These findings suggest that lipid peroxidation is related to the severity of preeclampsia, and hence, the administration of antioxidants to women at risk of preeclampsia would help to reduce the severity of preeclampsia.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]