Indian Journal of Medical Sciences Medknow Publications on behalf of Indian Journal of Medical Sciences Trust ISSN: 0019-5359 EISSN: 1998-3654 Vol. 57, Num. 8, 2003, pp. 335-337

Indian Journal of Medical Sciences, Volume 57, Number 8, August 2003, pp. 335-337

Low blood glutathione levels in acute myocardial infarction

Simmi Kharb

Department of Biochemistry, Pt. B.D. Sharma PGIMS, Rohtak, Haryana.
Correspondence: Dr. Simmi Kharb, H. No.1447, Sector-1, Urban Estate, Rohtak-124001, Haryana. E-mail : simmikh@rediffmail.com

Accepted Date: 15-04-2003

Code Number: ms03010

ABSTRACT

Background: Although experimental studies have demonstrated that reduced glutathione (GSH) is involved in cellular protection from deleterious effects of oxygen free radicals in ischaemia and reperfusion, there are controversial data on the correlation between levels of GSH and the ischaemic process. Aim: The present study was planned to evaluate erythrocyte GSH levels in patients with acute myocardial infarction (AMI). Setting & Design: Erythrocyte GSH levels were determined in 22 patients with AMI and 15 age matched healthy volunteers served as control. Material & Methods: Erythrocyte GSH levels were measured by using Bentler in AMI and control patients. Also lipid profile was analyzed enzymatically in these subject. Statistics: The values were expressed as means ± standard deviation (SD) and data from patients and controls was compared using student's `t'-test. Results & Conclusion: GSH levels were significantly decreased in AMI as compared to control (p<0.001). Also, total cholesterol and triglycerides were higher is AMI subjects (p<0.05). These finding suggest that depressed GSH levels may be associated with enhanced protective mechanism to oxidative stress in AMI.

Key Words: Erythrocyte GSH, Acute Myocardial Infarction (AMI).

INTRODUCTION

Glutathione (GSH), a cysteine containing tripeptide is the most abundant nonprotein thiol in the mammalian cells. It plays an important role in autoxidation of oxygen free radical (OFR) involved in diseases such as atherosclerosis, rheumatoid arthritis, adult respiratory distress syndrome or reoxygenation injury.¹ In vitro and in vivo studies on OFRs suggest that OFRs are toxic to the myocardium and can cause tissue damage that results in extensive necrosis, myocytolysis and cellular edema.² Among the enzymatic systems of protecting the cell against OFR injury, GSH, GSH peroxidase (GSHP), GSH reductase (GSSGR) and GSH transferase (GST) play a crucial role.³ Although experimental studies have demonstrated that reduced glutathione is involved in cellular protection from deleterious effects of OFRs in ischaemia and reperfusion, there are controversial data on the correlation between erythrocyte GSH and the ischaemic process.⁴ The present study was planned to evaluate erythrocyte GSH levels in patients with acute myocardial infarction (AMI).

MATERIAL & METHODS

Twenty two male patients with AMI and 15 age matched healthy volunteers were taken for this study.Informed consent was taken. Smoking habit, systolic and diastolic blood pressure and family history of coronary heart disease were recorded after clinical confirmation of AMI. All the patients had their first episode of MI with diagnostic criteria : typical chest pain, specific abnormalities for MI on electrocardiogram, elevated serum creatine phosphokinase (CP-MB) and / or aspartate aminotransferase enzyme levels. Patients with diabetes mellitus, renal insufficiency, hepatic disease or taking lipid lowering drugs or antioxidant vitamin supplements were excluded . Venous blood was collected before giving thrombolytic treatment, EDTA was added and samples were processed immediately in order to avoid GSH oxidation. GSH was measured by using the method of Beutler.⁵

Lipid profile (cholesterol, triglyceride (TG) and HDL-cholesterol) were analysed enzymatically before giving thrombolytic treatment. Malonaldehyde (MDA) levels were estimated by thiobarbituric acid reaction.⁷ The data from patients and controls were compared using student's t-test and values were expressed as means + standard deviation (SD).

RESULTS

GSH levels were significantly decreased in patients with AMI than in the controls (Table 1, p<0.001). MDA levels were significantly elevated in AMI patients as compared to control (p<0.05). Total cholesterol and triglycerides were higher in AMI subjects as compared to control (p<0.05). Also, significant differences were seen in HDL-C levels between AMI and controls. A statistically significant increase correlations was observed between rise in MDA and fall in GSH levels (r= -0.91, p <0.01). There was no correlation between GSH levels and cardiac enzyme concentrations, infarct localization and the frequency of arrhythmias.

DISCUSSION

Involvement of OFRs in the pathophysiology of inflammation, ischaemia and in reperfusion damage in a number of organs and tissues have been reported in literature.^1,6 Indirect evidence of OFR generation in patients with AMI has been observed by measuring a variety of by products of lipid peroxidation, such as pentane, conjugated dienes and malonaldehyde (MDA). In the present study, a significant increase in MDA levels was observed in patients with AMI.The plasma concentration of these substances have been reported to be elevated in patients with AMI in many studies.⁷ Reduction in infarct size in animal models of temporary coronary artery occlusion and reperfusion has been reported by means of several different anti- free radical interventions.⁸ OFRs are generated particularly in the early stage of MI and GSH is involved in the reduction of hydrogen peroxide radicals, resulting in a decrease in GSH levels during that period.^2,8 In the present study, low GSH levels were observed as compared to control. Ferrari et al⁹ observed a positive correlation between the duration of ischaemia in patients undergoing cardiopulmonary bypass and the efflux of oxidized GSH. Also, Blaustein et al¹⁰ demonstrated that GSH is important in protecting the myocardium against OFR injury and that a reduction in cellular GSH content would impair recovery after short periods of ischaemia. Depressed GSH levels may be associated with an enhanced protective mechanism to oxidative stress in AMI. In this study, we did not observe any correlation between GSH levels and the site of infarction or development of complications. Despite data linking OFR generation and reperfusion injury, there are reports that fail to show a beneficial effect of oxygen radical scavengers or other agents on infarct size reduction.¹¹ Further research including measurement of parameters of oxidative stress and comparative studies in patients with and without revascularization with thrombolytic therapy are ecessary in order to arrive at final conclusions about the role of GSH in AMI.

REFERENCES

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