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To study serum zinc levels in ischemic stroke patients

Sushree S Rautaray

Department of Biochemistry, Army College of Medical Sciences, Delhi, India

E-mail : bhuvaneswari.bibleraaj@uhsm.nhs.uk

Purnima Dey Sarkar

Department of Biochemistry, M.G.M Medical College, Indore, India

DOI: 10.15761/JTS.1000178

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Abstract

Stroke is the leading cause of mortality and morbidity worldwide, particularly in the elderly. Zinc is essential for the structure and function of regulatory, structural and enzymatic proteins and mediates various cellular and physiological functions. The aim of this study was to investigate the relationship between serum zinc and stroke outcome. Our study included 200 patients of ischemic stroke and 200 controls. Low serum zinc levels were reported in ischemic stroke patients compared to controls and a poor functional status at discharge.

Introduction

Stroke is the leading cause of disability worldwide and a serious neurological disease [1]. Ischemic strokes constitute 80-90% of all cases. The term stroke defines rapidly developing clinical symptoms and signs of focal loss of cerebral function lasting for more than 24 hours leading to death with no apparent cause other than vascular origin [2]. The increasing incidence of stroke in Indian patients (>65 years) is possibly due to industrialization, stress of life, less exercise, increasing incidence of smoking, hypertension and other factors. Zinc is one of the most abundant trace elements in the body. It mediates several vital physiological processes and functions and is essential for maintaining a healthy immune system and meeting metabolic demands [3]. However, whether zinc exerts neuroprotective effect during ischemic stroke is still unclear. Zinc is essential for the structure and function of regulatory, structural and enzymatic proteins. Zinc with calcium, potassium and sodium acts as a key modulator of neuronal excitability. The glutaminergic synapse is the most abundant synapse in the cerebral cortex and plays a pivotal role in cortical communications. Mean zinc levels in healthy cohorts range from 70 + 32 mcg/dl [4] to 105.2 mcg/dl [5,6]. These levels tend to decrease with age. We studied serum zinc levels in ischemic stroke patients and whether low zinc levels (<65 mcg/dl) are associated with higher stroke severity and poor functional status at discharge.

The study was case controlled in design. We have selected the patients as they have presented. Patients included in the present study were all admitted to the Intensive Care Unit (ICU) or attending the outpatient department of Medicine of Maharaja Yashvantrao Hospital attached to Mahatma Gandhi Memorial College, Indore (M.P). The study group consisted of 200 patients with ischemic stroke between 60-75 years of age and they were undergoing admission to hospital and 200 age and sex matched controls were taken with no family history of stroke. Brief clinical history covering the signs and symptoms, past, personal and family history of concerned risk factors were taken. All participants gave written informed consent and this protocol was approved by ethical and research committee of Mahatma Gandhi Memorial Medical College, Indore. Table-1 gives the details of the profiles of the subjects. The study was case controlled in design. We have selected the patients as they have presented. Patients included in the present study were all admitted to the Intensive Care Unit (ICU) or attending the outpatient department of Medicine of Maharaja Yashvantrao Hospital attached to Mahatma Gandhi Memorial College, Indore (M.P), India.

The study group consisted of 200 patients with ischemic stroke between 60-75 years of age and they were undergoing admission to hospital and 200 age and sex matched controls were taken with no family history of stroke. Brief clinical history covering the signs and symptoms, past, personal and family history of concerned risk factors were taken. All participants gave written informed consent and this protocol was approved by ethical and research committee of Mahatma Gandhi Memorial Medical College, Indore. Table-1 gives the details of the profiles of the subjects. Blood samples were analyzed by atomic absorption spectroscopy; the reference range was 65-150 mcg/dl.

M.K. Chooi et al., studied low zinc levels to be defined as <65mcg/dl. We divided zinc levels into two groups: low levels (<65 mcg/dl) and normal levels (>65 mcg/dl) [4-6].

The study group consisted of 200 patients with ischemic stroke between 60-75 years of age and they were undergoing admission to hospital and age and sex matched controls were taken with no family history of stroke. Brief clinical history covering the signs and symptoms, past, personal and family history of concerned risk factors were taken. All participants gave written informed consent and this protocol was approved by ethical and research committee of Mahatma Gandhi Memorial Medical College, Indore. Table-1 gives the details of the profiles of the subjects. Blood samples were analyzed by atomic absorption spectroscopy.

Statistical Analysis All values are presented as mean + s.d. Statistical significance was analysed by student ‘t’ test and correlation between variables were studied by using Pearson’s correlation coefficient test. The level of significance was set at p<0.05.

Table 1: Baseline characteristics of study subjects

Particulars

Patients (n=200)

Controls (n=200)

Age (years)

70.2  ± 19

68.2 ± 16

Male/ Female

130/ 70

125/ 75

HTN (%)*

116%

52%

*HTN= Hypertension

Results

The clinical characteristics of Ischemic stroke patients and control subjects are presented in Table No. 1. Among 200 Ischemic stroke patients, 130 were males and 70 were females. Among 200 controls 125 were males and 75 were females.

The clinical and biochemical characteristics of the patients and controls is described in Table No. 2

Table 2: Characteristics of patients with Ischemic Stroke and association with low Zinc levels (< 65 mcg/dl)

 

Total N = 200

Zinc level N=100

(< 65 mcg/dl)

Zinc level N=100

(> 65 mcg/dl)

P value

Mean age yrs

(mean + SD)

66.2 + 19

70.2 + 20

68.2 + 16

P < .05*

Males (N)

100

50

50

P < .05*

Hypertension (N)

40

30

30

P < .001**

Smoking (N)

40

20

20

P < .001**

*P – value < .05 = Significant
**P- Value < .001 = Highly Significant

Discussion

The study was conducted on 200 confirmed cases of ischemic stroke patients and 200 age and sex matched controls. Our study showed that lower zinc levels (<65mcg/dl) are associated with ischemic strokes with poor functional status at discharge. It is still unclear that whether zinc is neuroprotective or neurotoxic or both [3]. Several studies have demonstrated that increased intracellular zinc levels [7,8] during ischemic stroke may enhance neuronal death [7]. Preclinical studies have demonstrated the role of zinc in cerebral ischemia and stroke. Animal based studies have shown that zinc supplementation reduces infarct size [9], while zinc chelation is neurotoxic.

Bhatt et al., studied low serum zinc levels in 35.7% patients of ischemic stroke and poor functional staus discharge [10]. Munshi et al., reported that low zinc levels is an independent risk factor for stroke [11]. Sorensen et al., reported the disappearance of zinc positive neuronal terminals in the ischemic neocortex and related areas,most likely due to a neuronal release of vesicular zinc in response to hypoxia,and concluded that the high extracellular concentration of zinc is thought to be neuroprotective by blocking the receptors [12]. Alteration of zinc levels in brain may influence neurotransmission in zinc containing glutaminergic synapses. Therefore dietary zinc deficiency may influence zinc homeostasis in the brain, resulting in brain dysfunction such as stroke. A Munshi et al., reported low zinc levels may be in fact a risk for stroke [12].

The results of this study show that zinc is found to be deficient in patients with ischemic stroke. The development of new treatment and preventive strategies need to be taken into account for the role of zinc in neuronal function, damage and repair. Further studies are required to delineate the importance of serum zinc levels in patients with ischemic stroke and to investigate whether low zinc levels are associated with long term outcomes.

References

  1. Bronner LL, Kanter DS, Manson JE (1995) Primary prevention of stroke. N Engl J Med 333: 1392-1400. [Crossref]
  2. Dalal PM (2001) Ischaemic strokes: management in first six hours. Neurol India 49: 104-115. [Crossref]
  3. Galasso SL, Dyck RH (2007) The role of zinc in cerebral ischemia. Mol Med 13: 380-387. [Crossref]
  4. Chooi MK, Todd JK, Boyd ND (1976) Influence of age and sex on plasma zinc levels in normal and diabetic individuals. Nutr Metab 20: 135-142. [Crossref]
  5. Buxaderas SC, Farré-Rovira R (1985) Whole blood and serum zinc levels in relation to sex and age. Rev Esp Fisiol 41: 463-470. [Crossref]
  6. Sandstead HH, Henriksen LK, Greger JL, Prasad AS, Good RA (1982) Zinc nutriture in the elderly in relation to taste acuity, immune response, and wound healing. Am J Clin Nutr 36: 1046-1059. [Crossref]
  7. Shabanzadeh AP, Shuaib A, Yang T, Salam A, Wang CX (2004) Effect of zinc in ischemic brain injury in an embolic model of stroke in rats. Neurosci Lett 356: 69-71. [Crossref]
  8. Tønder N, Johansen FF, Frederickson CJ, Zimmer J, Diemer NH (1990) Possible role of zinc in the selective degeneration ofdentate hilar neurons after cerebral ischemia in the adult rat. Neuroscience Letters 109: 247-252. [Crossref]
  9. Kadoya C, Domino EF, Yang GY, Stern JD, Betz AL (1995) Preischemic but not postischemic zinc protoporphyrin treatment reduces infarct size and edema accumulation after temporary focal cerebral ischemia in rats. Stroke 26: 1035-1038. [Crossref]
  10. Bhatt A, Farooq MU, Enduri S, Pillainayagam C, Naravetla B, et al. (2011) Clinical significance of serum zinc levels in cerebral ischemia. Stroke Res Treat 2010: 245715. [Crossref]
  11. Munshi A, Babu S, Kaul S, Shafi G, Rajeshwar K, et al. (2010) Depletion of serum zinc in ischemic stroke patients. Methods Find Exp Clin Pharmacol 32: 433-436. [Crossref]
  12. Sørensen JC, Mattsson B, Andreasen A, Johansson BB (1998) Rapid disappearance of zinc positive terminals in focal brain ischemia. Brain Res 812: 265-269. [Crossref]

Editorial Information

Editor-in-Chief

Terry Lichtor

Article Type

Research Article

Publication history

Received date: January 28, 2017
Accepted date: February 10, 2017
Published date: February 13, 2017

Copyright

© 2017 Rautaray SS. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Citation

Rautaray SS, Sarkar PD (2017) To study serum zinc levels in ischemic stroke patients. J Transl Sci 3: DOI: 10.15761/JTS.1000178

Corresponding author

Sushree S Rautaray

Department of Biochemistry, Army College of Medical Sciences, Delhi, India

Table 1: Baseline characteristics of study subjects

Particulars

Patients (n=200)

Controls (n=200)

Age (years)

70.2  ± 19

68.2 ± 16

Male/ Female

130/ 70

125/ 75

HTN (%)*

116%

52%

*HTN= Hypertension

Table 2: Characteristics of patients with Ischemic Stroke and association with low Zinc levels (< 65 mcg/dl)

 

Total N = 200

Zinc level N=100

(< 65 mcg/dl)

Zinc level N=100

(> 65 mcg/dl)

P value

Mean age yrs

(mean + SD)

66.2 + 19

70.2 + 20

68.2 + 16

P < .05*

Males (N)

100

50

50

P < .05*

Hypertension (N)

40

30

30

P < .001**

Smoking (N)

40

20

20

P < .001**

*P – value < .05 = Significant
**P- Value < .001 = Highly Significant