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Year : 2013 | Volume : 1 | Issue : 1 | Page : 20 - 22  


Original Articles
Malondialdehyde as a marker of lipid peroxidation in acute myocardial infarction patients

Shilpa H D1, Anita R Bijoor2

1 Assistant professor,Dept of Biochemistry, Malla Reddy Institute of Medical Sciences, Suraram, Hyderabad, 2 Professor & HOD, Dept of Biochemistry, St Johns Medical College, Bangalore

                                     

Abstract:

Background: There is growing evidence that increase in free radical production and impaired antioxidant activity is important in the pathogenesis of acute myocardial infarction(AMI).increased lipid peroxidation is thought to be a consequence of lipid peroxidation which occurs when the dynamic balance between prooxidant and antioxidant mechanism is impaired. Malondialdehyde (MDA) is one of the most frequently used indicators of lipid peroxidation. It is one of the several byproducts of lipid peroxidation processes. Objective: The objective of this study was to evaluate the role of lipid peroxidation through measuring the MDA levels in cases of AMI and also to find out the changes in the levels of MDA through the course of the disease. Methods: A total of 30 patients were eligible for the study who met the inclusion and exclusion criteria. Blood sample was collected from these patients on the day of admission (day 0), 12-30 hrs after collecting the first sample (day 1), and 35-54 hrs after collecting the second sample (day 2). The patients were followed up to their discharge. MDA levels were estimated in the plasma by thiobarbituric acid (TBA) method. Results: This study showed a statistically significant increase in the MDA levels during the course of the study. Conclusion: There is clear evidence from this study and various other studies that there is a definite increase in the lipid peroxidation products in the event of AMI.Whether These changes, primary or secondary to the event, have any bearing on the prognosis of the patient and whether MDA can be used as a prognostic marker have to be investigated further.

Key words: MDA, lipid peroxidation, AMI

 

Corresponding Author: Dr Shilpa HD, Assistant Professor, dept of biochemistry, Mallareddy Institute of Medical sciences, Suraram, Hyderabad.              

Email-shilpadhruva@gmail.com

 

INTRODUCTION:

Malondialdehyde plays a crucial role in the development and prognosis of atherogenic events.MDA is a product of lipid peroxidation. Malondialdehyde modified low density lipoprotein (LDL) can be recognized and taken up by macrophages via scavenger receptors, causing massive internal accumulation of cholesterol esters. [1, 2]

Lipid peroxidation can be considered one of the mechanisms through which several cardiovascular risk factors like smoking, increased serum triglycerides, low high density lipoprotein (HDL); Low vitamin C may promote cardiovascular disease. [3]

This study was undertaken to find out the utility of MDA as a marker of lipid peroxidation, an event which plays a significant role in the development of and prognosis of AMI.

Lipid peroxidation is initiated by the attack on a fatty acid or fatty acyl side chain of any chemical species that has sufficient reactivity to abstract a hydrogen atom from a methylene carbon in the side chain. The greater the number of double bonds in a fatty acid side chain, the easier is the removal of a hydrogen atom, which is why polyunsaturated fattyacids are particularly susceptible to peroxidation.

Extensive lipid peroxidation in biological membranes causes loss of fluidity , falls in membrane potential , increased permeability to hydrogen and other ions and eventual rupture leading to release of cell and organelle contents. Some end products of peroxide fragmentation are also cytotoxic. [4]

A wide variety of techniques has been used to show that lipid peroxidation increases in many diseases and in tissues poisoned by a variety of toxins. Disrupted tissues undergo lipid peroxidation more quickly than healthier ones.[5] Reason for this increased peoxidability of damaged tissues include inactivation of some antioxidants , leakage of antioxidants from the cell, and the release of metal ions (especially iron and copper) from storage sites and from metalloproteins hydrolysed from enzymes released from damaged lysosomes. Hence this series of events Disease or toxin →cell death or damage →increased lipid peroxidation can explain many of the reports of increased lipid peroxidation in disease or toxicology. [6]

When LDL is isolated from normal human plasma and subjected to oxidative stress by adding micromolar amounts of copper salt, a lag period occurs before the onset of detectable lipid peroxidation. This lag period is taken as an index of antioxidant potential of the LDL molecule. When LDL antioxidants such as vitamin E, beta-carotene, lycopene, and phytofluene are fully depleted, the lag phase (1 hr) ends and peroxidation accelerates by propogation (1 hr) and continues for several hours as the decomposition reaction produces aldehydes responsible for cytotoxicity and macrophage uptake of LDL. All the vitamin E presented in LDL is consumed during the first 10 minutes of the lag phase, followed by the other lipid soluble antioxidants during the next 40-50 minutes.Vitamin E is the most abundant antioxidant in LDL, there being around 6 molecules per LDL particle. The other lipid soluble antioxidants contain less than 1 molecule per LDL particle. [4]

Lipid peroxidation can be considered one of the mechanisms through which several cardiovascular risk factors like smoking, increased serum triglycerides, low HDL; Low vitamin C may promote cardiovascular disease. [3]

Malondialdehyde is one of the most frequently used indicators of lipid peroxidation . It is one of the several byproducts of lipid peroxidation processes.Malondialdehyde plays a crucial role in the development and prognosis of atherogenic events. Malondialdehyde modified LDL can be recognized and taken up by macrophages via scavenger receptors, causing massive internal accumulation of cholesterol esters. Since other markers of lipid peroxidation are quite unstable and difficult to estimate, in this study, MDA,which is a useful indicator of lipid peroxidation and the estimation of which is easier owing to the stable analyte properties etc,was selected as a marker of lipid peroxidation.[3,5,6]

 

Materials and Methods:

Study design: A Prospective clinical study consisting of 30 patients with acute myocardial infarction is undertaken to study the changes in MDA (marker of lipid peroxidation) in acute myocardial infarction patients.

Written informed consent was taken from all the patients and the study was approved by the institutional ethical committee.

The source of data were the patients diagnosed as acute ST segment elevation myocardial infarction using the standard guidelines of ACC/AHA (using ECG/cardiac enzymes) from St John’s hospital, Bangalore.

A total of 30 patients were eligible for the study who met the inclusion and exclusion criteria. Blood sample was collected from these patients for estimation of MDA on the day of admission (day 0), 12-30 hrs after collecting the first sample (day 1), and 35-54 hrs after collecting the second sample (day 2). The patients were followed up to their discharge.

Inclusion criteria:

  1. All patients of ST segment elevation myocardial infarction (STEMI) who is not thrombolysed.
  2. Age group- 30 to 65 yrs

Exclusion criteria:

  1. Cases of myocardial infarction who have or who are going to receive thrombolytic therapy of any kind
  2. Patients who have or who develop renal complications / cerebral complications during the course of the study
  3. Patients with gout.
  4. Cases of non ST segment elevation myocardial infarction.

Estimation of total Malondialdehyde in Plasma. [3, 7]

AIM: To estimate total Malondialdehyde (MDA) in the plasma by Thiobarbituric acid (TBA) method.

PRINCIPLE: This assay is based upon the reaction of TBA with MDA, one of the aldehyde products of lipid peroxidation. The sample is heated with PDA under acidic condition and the intensity of the pink chromogen of MDA – PDA adduct is measured at 532nm in a spectrophotometer .

Statistical Methods: Descriptive statistical analysis has been carried out in the present study. Results on continuous measurements are presented on Mean ± SD (Min-Max) and results on categorical measurements are presented in Number (%). Significance is assessed at 5 % level of significance. Repeated Measures Analysis of variance (RMANOVA) has been used to find the significance of study parameters between three or more groups of patients ,Student t test ( two tailed, independent) has been used to find the significance of study parameters on continuous scale between two groups Inter group analysis) Chi-square/ Fisher Exact test has been used to find the significance of study parameters on categorical scale between two groups. 90% Confidence Interval has been computed to find the significant features. Confidence Interval with lower limit more than 50% is associated with statistical significance.

 

Results and Discussion:

 

Figure 1: Age distribution of patients studied

 

 

Figure 2. Gender distribution of patients studied

 

 

 

 

Figure 3: EVALUATION OF STUDY PARAMETER DURING THE COURSE OF STUDY

 

Parameter

Day 0

Day 1

Day 2

Result

Plasma Melondialdehyde levels (mmol/L)

6.80±1.08

(4.80-8.70)

7.43±1.05

(5.0-9.2)

7.84±1.44

(5.0-10.2)

F=14.942;

P<0.001**

 

Figure 3 and above table shows the mean levels of plasma MDA. On day 0, the mean plasma MDA was 6.80+1.08(4.8-8.7), on day 1 it was 7.43+1.05(5.0-9.2), on day 2 it was 7.84+1.44(5.0-10.2) with a p value of< 0.001.

 

Table 1 shows the increase and decrease in the levels of MDA in patients after AMI.

 

Table 1: The increase and decrease in the levels of Melondialdehyde

 

Parameter                

Increased

Decreased

Total

Plasma

Melondialdehyde

levels (mmol/L)

24

(80.0%)

6(20.0%)

30

 

This study shows a significant increase in MDA levels between day 0 and day 2. In their study, Domanski L et al[8] studied plasma MDA, uric acid and white cell count as markers of oxidative stress in patients with AMI.40 patients with acute myocardial insufficiency in the age group 40-66 and 22 healthy volunteers were included in the study and it was found that patients with AMI had elevated MDA levels and they concluded that elevated levels of MDA in patients with AMI may reflect secondary disorders of cellular metabolism and late appearance of degradation products of lipid peroxides. Various other studies have also shown a significant role of MDA in atherogenesis and ischemic events like myocardial infarction. [2, 9, 10, 4] This study is in agreement with these above stated studies which showed a significant increase in MDA values in AMI.

 

MDA reflects both auto-oxidation and free radical mediated peroxidation of unsaturated fatty acids. [11] In AMI patients a significant increase in lipid peroxidation was observed in the days following the acute event, reaching a maximum value in 6-8 days. A crucial role in conversion of reversible damage to irreversible damage is played by cardiomyocyte membrane destruction caused by the so called lipid triad. This comprises of stimulation of lipid peroxidation, activation of phospholipases, and the detergent like action of excessive amounts of free fatty acids and lysophospholipids. Marked activation of lipid peroxidation in myocardial infarction has been demonstrated in earlier studies also. [12] This reasons out the increase in levels of MDA after AMI due to free radicals.

Lipid per oxidation of membrane polyunsaturated fatty acids by reactive oxygen species is considered the major mechanism of ischemia-reperfusion injury. Total free radical trapping ability is an accurate index of oxidative stress, which provides a measure of total plasma defenses against reactive oxygen species.[13]

Oxidative stress is a condition in which oxidant metabolites exert their toxic effect because of an increased production or an altered cellular mechanism of protection. The heart needs oxygen avidly and, although it has powerful defense mechanism, it is susceptible to oxidative stress, which occurs, for instance, during Ischemia. Ischemia causes alterations in the defense mechanism against free radicals, mainly a reduction in the activity of mitochondrial superoxide dismutase and a reduction in the tissue content of reduced glutathione. At the same time, production of free radicals increases in mitochondria and leukocytes and toxic oxygen metabolite production is exacerbated by readmission of oxygen during reperfusion. Oxidative stress in turn causes oxidation of thiol groups and lipid peroxidation leading first to reversible damage and eventually to necrosis. [14, 15]

Conclusion:

Lipid peroxidation plays a very important role in the pathogenesis of myocardial infaction. The marker of lipid peroxidation, Malondialdehyde (MDA) showed a significant increase in the course of the illness in this study. The clinical utility of MDA as a marker in AMI and whether such an increase is primary or secondary to the changes and other risk factors in AMI needs further investigation.

 

 References:

 

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