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Table of Contents
ORIGINAL ARTICLE
Year : 2019  |  Volume : 6  |  Issue : 2  |  Page : 58-64

Oxidative stress and biomarker of tumor necrosis factor-alpha, malondialdehyde, and ferric reducing antioxidant power in hypertension


1 Department of Biochemistry, GSVM Medical College, Kanpur, Uttar Pradesh, India
2 Department of Biochemistry, Moti Lal Nehru Medical College, Allahabad, India
3 Department of Biochemistry, Santosh Medical College and Hospital (Santosh University), Ghaziabad, Uttar Pradesh, India

Date of Web Publication18-Nov-2019

Correspondence Address:
Dr. Anand Narayan Singh
Department of Biochemistry, GSVM Medical College, Kanpur, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ami.ami_34_19

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  Abstract 

Background: Concurrent with the imbalance of oxidizing agents and antioxidants, high blood pressure (BP) is a major physical condition burden in the current scenario. Tumor necrosis factor-alpha (TNF-α) plays a vital role in the pathogenesis of hypertension (HTN). TNF-α inhibitor improves clinical symptoms; however, their outcome on high BP has not been investigated. We investigated the inflammatory marker TNF-α, malondialdehyde (MDA), and ferric reducing antioxidant power (FRAP) in hypertensive patients. We measured BP randomly using an ambulatory observe in hypertensive patients. Measured systolic BP was 140 mmHg and/or diastolic BP was 90 mmHg were considered hypertensive. Materials and Methods: A total of 60 cases were considered in the study involving 30 hypertensive patients and 30 normal controls (30). Measurements of serum concentrations of TNF-α, MDA, and FRAP in HTN patients were done in both the groups. Results: Serum TNF-α was found to be remarkably increased in study participants as compared to the normal group (r = 0.32,P < 0.0001*). Serum MDA was also raised in hypertensive as compared to the control group (r = 0.99**,P < 0.0001*), whereas serum FRAP was found to be decreased in the hypertensive group in comparison to the healthy controls (r = 0.23,P < 0.0001*). Conclusions: It is concluded that high BP leads to the generation of oxidative stress with a remarkable elevation of TNF-α and MDA levels. The indicates decrease level of Ferric Reducing Antioxidant Power (FRAP) and suggest a possible role of oxidative stress in the pathophysiology of hypertension.

Keywords: Biomarker, blood pressure, hypertension, reactive oxygen species


How to cite this article:
Verma MK, Jaiswal A, Sharma P, Kumar P, Singh AN. Oxidative stress and biomarker of tumor necrosis factor-alpha, malondialdehyde, and ferric reducing antioxidant power in hypertension. Acta Med Int 2019;6:58-64

How to cite this URL:
Verma MK, Jaiswal A, Sharma P, Kumar P, Singh AN. Oxidative stress and biomarker of tumor necrosis factor-alpha, malondialdehyde, and ferric reducing antioxidant power in hypertension. Acta Med Int [serial online] 2019 [cited 2019 Dec 6];6:58-64. Available from: http://www.actamedicainternational.com/text.asp?2019/6/2/58/271113


  Introduction Top


Hypertension (HTN) is a main health problem in developed as well as developing countries with a common result of elevated blood pressure (BP). HTN is present in 60%–70% of the population over 60 years of age and may result in cardiovascular complications such as stroke, coronary heart disease, and heart failure.

High BP (essential HTN) is defined as systolic pressure >140 and/or diastolic pressure >90. Patients with systolic BP (SBP) between 120 and 139 or diastolic BP (DBP) of 80–89 are considered “prehypertensive” and need medical monitoring and lifestyle changes.[1] Oxidative stress is caused by imbalance between the production of reactive oxygen species (ROS) and the ability of a biological system to readily detoxify the reactive intermediates improved vascular oxidative stress, the resulting damage. This could be considered to the pathogenesis of high Blood Pressure, a major factor cause for heart disease mortality.[2],[3]

Oxidative stress causes of imbalance between the generations of ROS, the antioxidant as a Free Radical Scavenger Systems.[4],[5] In human high BP, ROS may raise due to a decrease in the activity of antioxidant enzymes.[6] The significance of ROS in the vascular role of the development of high BP has been recently reviewed.[7],[8] The relationship between high BP, oxidative stress, and antioxidants is complex and inadequately understood. Oxidative stress may play a role in the pathophysiology of HTN. Human and animal studies have demonstrated that HTN is accompanied by an increase in oxidative stress.

However, the evidence for this in humans is not definitive.[9] Past Studies demonstrate the hypertension may development as a result of increase ROS[10] Hypertensive effects of oxidative stress are mostly due to endothelial dysfunction resulting from disturbances of vasodilator systems, particularly degradation of nitric oxide by oxygen-free radicals.[11],[12]

Other studies were following with the aim to measure the levels of malondialdehyde (MDA) during hypertensive conditions. Elevated serum MDA levels in hypertensive patients as compared to normotensive control individuals.[13] Elevated levels of serum MDA and decreased catalase activity were found in hypertensive pregnant women as compared to a healthy person.[14] EI-Bana et al.[15] studied the maternal and cord plasma concentration of MDA in preclamptic and healthy pregnant women.

The concentration of MDA in preclamptics was found to be significantly lower in cord plasma as compared to the maternal plasma (the fetus from oxidative injury due to increased oxidative stress of a preclamptic mother). MDA is a useful biomarker for lipid peroxidation and oxidative stress. Increased levels of oxidative stress have been associated with various disease patterns.

Ferric reducing antioxidant power (FRAP) had the highest correlations with BP among the oxidative stress-related parameters studied because of the relationship between oxidative stress and HTN; it is worth noting that drugs with antioxidant effects can also be expected to lower BP.[16] In addition, the administration has been shown to cause a decrease in oxidative stress in hypertensive.[17],[18] Along these lines, antioxidant vitamins have been shown to exert antihypertensive effects in spontaneously hypertensive although the extensibility of these results to human beings remains controversial.[19]

Despite the progress in its diagnosis and treatment, the etiology of HT remains unclear and a matter of substantial debate. It is widely acknowledged that the function of the vascular system, kidneys, and sympathetic nervous system is critical for the control and maintenance of BP.[20] Vascular resistance, stiffness, and remodeling as well as endothelial dysfunction are hallmarks of HT.[21],[22],[23],[24] The present study was to elucidate the MDA and FRAP in HTN with and without HTN.


  Materials and Methods Top


Clinically diagnosed and confirmed cases of hypertension in the age group of 25–74 years. The study was approved by the institute ethics committee, and informed consent was obtained from all the cases and controls.

Inclusion

The case group included hypertensive patients with average BP ≥140/90 mmHg for a period >10 years, as defined by the JNC 7th criteria.[25]

Exclusion

Patients with renal disorders, diabetes mellitus, liver disorder, gout, and familial hyperlipidemia were expelled. Furthermore, patients those who were on antioxidants, vasoactive medicine, and lipid-lowering statins were expelled.

Sample collection and storage

Under aseptic conditions, 5 ml of whole blood were collected. Of this, 1 ml was collected in fluoride vial estimation of blood sugar fasting and 4 ml collected in without anticoagulant (plain) estimate of MDA and estimate of FRAP, estimate of tumor necrosis factor-alpha (TNF-α), estimate of serum creatinine, and estimate of blood sugar fasting centrifuged (3000 rpm, for 3–5 min at 37°C) to obtain serum that was also stored at −80°C for further biochemical measurements.

Numbers of cases selected for the study:

  • 30 cases of HTN patients
  • 30 controls of normal persons.


Biochemical measurement

  1. Estimation of MDA by Satoh method[26]
  2. FRAP assay kit[27]
  3. Estimation of human TNF-α immunoassay by sandwich-enzyme immunoassay[28]
  4. BP measured by sphygmomanometer.



  Results Top


A total of 60 samples were considered in the study, of which 30 were HTN patients and 30 were normal individuals.

As shown in [Table 1], in the HTN group, 11 (36.7%) patients were female and 19 (36.3%) were male, whereas in the normal group, there were 12 (40%) male and 18 (40.0%) female persons.
Table 1: Frequency distribution among male and female in normotensive persons

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As shown in [Table 2], in the normal individual group, all the serum values were in the normal range. The MDA levels of HTN patients and normotensive (control) group were extremely significance (P < 0.0001). The FRAP levels of HTN patients and normotensive (control) group were highly significant (P < 0.0001). The TNF-α levels of HTN patients and normotensive group were highly significant (P < 0.0001). The SBP levels of HTN patients and normotensive (control) group were highly significance (P < 0.0001). The DBP levels of HTN patients and normotensive (control) group were highly significance (P < 0.0001).
Table 2: Clinical characteristics of normotensive and hypertensive patients participating in the study

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[Table 3] and [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5] shows the correlation matrix which represents the quantitative measurements of degree of relationship among different variables. It showed that MDA and FRAP were mildly correlated (r = 0.118, P = 0.536) in cases. There is a negative correlation between MDA and SBP (r = −0.073, P = 0.0700). There is a negative correlation between FRAP and TNF-α (r = −0.040, P = 0.834). There is a negative correlation between FRAP and SBP (r = −0.173, P = 0.360). There is a negative correlation between FBS and TNF-α (r = −0.194, P = 0.303). There is a negative correlation between SBP and FRAP (r = −0.173, P = 0.360). There is a negative correlation between SBP and TNF-α (r = −0.092, P = 0.629).
Table 3: Pearson's correlation coefficient among the biochemical parameters in cases

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Figure 1: Scatter diagram showing an association between malondialdehyde and ferric reducing antioxidant power in cases

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Figure 2: Scatter diagram showing the association between malondialdehyde and tumor necrosis factor-alpha in cases

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Figure 3: Scatter diagram showing the association between malondialdehyde and fasting blood sugar in cases

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Figure 4: Scatter diagram showing the association between SBP and DBP in cases

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Figure 5: Scatter diagram showing the association between ferric reducing antioxidant power and tumor necrosis factor-alpha in cases

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[Table 4] and [Figure 6], [Figure 7], [Figure 8], [Figure 9] shows the correlation matrix which represents the quantitative measurements of degree of relationship among different variables. It showed that MDA and FRAP were mildly correlated (r = 0.329, P = 0.076) in control group. There is a negative correlation between MDA and TNF-α (r = −0.443, P = 0.014). There is a negative correlation between FBS and TNF-α (r = −0.111, P = 0.559). There is a negative correlation between MDA and DBP (r = −0.038, P = 0.842). There is a negative correlation between FRAP and TNF-α (r = −0.348, P = 0.060). There is a negative correlation between DBP and FRAP (r = −0.254, P = 0.176). There is a negative correlation between TNF-α to FBS, SBP, DBP (r = −0.142, P = 0.453; r = -0.161, P = 0.0.396, r = -0.012, P = 0.948)
Table 4: Pearson's correlation coefficient among the parameters in controls

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Figure 6: Scatter diagram showing the association between malondialdehyde and ferric reducing antioxidant power in controls

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Figure 7: Scatter diagram showing the association between malondialdehyde and tumor necrosis factor-alpha in controls

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Figure 8: Scatter diagram showing the association between SBP and DBP in controls

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Figure 9: Scatter diagram showing the association between malondialdehyde and fasting blood sugar in controls

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  Discussion Top


The present study to reveal that coronary endothelial dysfunction is separately associated with elevation of the plasma pro-inflammatory cytokines TNF-α in patients with Hypertension. In addition, elevated plasma TNF-α levels' strength is helpful for identifying the elevated risk of high-BP patients with coronary endothelial dysfunction.

In their study, we have determined the levels of some endogenous antioxidants in important to hypertensive participants and compared with their age- and sex-matched healthy persons. This study is the first to evaluate the correlation among necrosis factor and oxidative stress markers in hypertensive patients. Oxidative stress is an occurrence which is moreover due to excessive production of ROS. Undernourishment can lead to a reduction of antioxidant.[29],[30],[31],[32]

Past study was oxidative stress through hydrogen peroxide raised phosphorylation of tyrosine kinase, leads to binding of neutrophil on endothelium and implementation in vessel permeability.[33] It was notable that FRAP correlations with BP among the oxidative stress-related parameters studied. Because of the relationship between oxidative stress and high BP, it is worth noting that drugs with antioxidant effects can also be expected to lower BP.

Accordingly, the antihypertensive effects of statins could arise from their antioxidant properties, via their ability to decrease the expression of NADPH oxidase subunits and up regulate catalase expression in vivo. Along these lines, antioxidant vitamins have been shown to exert antihypertensive effects in spontaneously hypertensive rats, although the extensibility of these results to human beings remain controversial, and awaits the completion of large scale clinical trials that are currently underway.

The present study justified that FRAP was not elevated in hypertensive patients compared with healthy controls and that there was a negative association between TNF-α (r = −0.040, P = 0.834) and coronary endothelial dysfunction. This observation indicates that TNF-α, rather than FRAP and MDA, is useful for identifying coronary vascular dysfunction in hypertensive patients.


  Conclusions Top


The role of serum Tumor Necrosis Factor- Alpha levels are increase and Malondialdehyde was elevated and Ferric Reducing Antioxidant Power was decrease prominent in Hypertension. In addition, it is supplementary to the recent literature in hold of oxidative stress having a pathogenic role in the growth of Hypertension and recommends antioxidants therapies and antioxidants intake of diet. The pathophysiological substrate of these interrelationships needs further investigation through large-scale prospective studies.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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