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 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 12  |  Issue : 3  |  Page : 114-117

To study the role of magnesium and Gamma- glutamyl transferases in alcoholic liver disease


1 Department of Biochemistry, Shyam Shah Medical College, Rewa, Madhya Pradesh, India
2 Department of Musculoskeletal Sciences, Datta Meghe College of Physiotherapy, Nagpur, Maharashtra, India
3 Department of Preventive and Social Medicine, Indira Gandhi Government Medical College, Nagpur, Maharashtra, India

Date of Submission18-Jun-2021
Date of Decision23-May-2022
Date of Acceptance26-May-2022
Date of Web Publication30-Jun-2022

Correspondence Address:
Dr. Kapila Gaikwad
New Doctor's Colony, F16/1, Ground Floor, Arjun Nagar, Near Dhobia Tank, Rewa - 486 001, Madhya Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/cmrp.cmrp_63_21

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  Abstract 


Aim: To study the role of magnesium and gamma- glutamyl transferases in alcoholic liver disease.
Objectives: (1) To estimate serum magnesium and serum glutamyl-transferases (GGT) in alcoholic liver disease. (2) To estimate liver enzymes Alanine Transaminases (ALT), Aspartate Transaminases (AST), Alkaline Phosphatase (ALP), and Total protein and Albumin in alcoholic liver disease. (3) To correlate serum magnesium with all liver enzymes. (4) To correlate serum GGT with all liver enzymes.
Materials and Methods: All liver enzymes, serum magnesium, serum GGT, total protein and albumin were estimated in 50 alcoholic liver disease patients and 50 normal subjects on Trivitron Dirui autoanalyzer.
Results: Significant difference was found between mean values of cases and controls in Mg, GGT, AST, ALT, Alkaline phosphatase, and Albumin (P<0.05). Positive correlation was found between Mg with GGT, ALT, Total proteins and Albumin. This indicates that the higher(lower) values of Mg are associated with higher(lower) values of GGT, ALT, Total proteins, and Albumin. But the result were not statistically significant.(P >0.05).
Conclusion: Chronic alcoholic liver disease significantly elevates Gamma-glutamyl transferase. Hypomagnesemia is also seen in alcoholic liver disease. Gamma-glutamyltransferase has a significant relation with magnesium levels in alcoholic liver disease.

Keywords: Magnesium, Gamma-glutamyltransferase, Alcoholic liver disease


How to cite this article:
Gaikwad K, Selkar S, Agrawal S. To study the role of magnesium and Gamma- glutamyl transferases in alcoholic liver disease. Curr Med Res Pract 2022;12:114-7

How to cite this URL:
Gaikwad K, Selkar S, Agrawal S. To study the role of magnesium and Gamma- glutamyl transferases in alcoholic liver disease. Curr Med Res Pract [serial online] 2022 [cited 2022 Aug 12];12:114-7. Available from: http://www.cmrpjournal.org/text.asp?2022/12/3/114/349297




  Introduction Top


Alcoholic liver disease (ALD) is a term that includes the liver manifestations of alcohol overconsumption, including fatty liver, alcoholic hepatitis and chronic hepatitis with liver fibrosis or cirrhosis.[1] Early ALD remains usually undiagnosed and is usually discovered when liver enzyme levels are found to be elevated. Some other biomarkers which are been recently introduced and very little research is done are magnesium (Mg) and gamma-glutamyl transferase (GGT) in ALD. Mg insufficiency aggrevates cirrhosis. There is a negative impact on mitochondrial bioenergetics due to decrease in intracellular Mg content. This leads to decreased ATP production and hepatocyte damage, thus aggrevating liver cirrhosis.[2]

Increased serum GGT activities associated with alcoholism might be due to increased GGT activity from the liver due to hepatic injury or due to hepatic enzyme induction.[3]

This study was aimed to find the role of Mg and GGT in ALD.


  Materials and Methods Top


Institutional Ethical Approval was obtained before the commencement of the study. This study was done at a tertiary care centre. The study duration was from January 2017 to September 2017. Informed written consents were taken from patients.

Demographic details

The study population comprised 50 patients of age group of 25–70 years diagnosed with ALD. Fifty participants of a similar age group without a history of alcohol intake were taken as controls. Participants with fatty liver or liver injury due to causes other than alcohol, subjects on antacids containing Mg and loop diuretics containing Mg were excluded from the study.

Collection of samples

Five ml of blood sample was collected in plain red top tube containing no anticoagulant, serum was separated and used for the study.

Liver function tests including aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), serum GGT and serum Mg were estimated on Trivitron Dirui autoanalyser.

Serum magnesium-xylidyl blue method[4]

This is a direct method where Mg forms a coloured complex with xylidyl blue in a strongly basic solution, where calcium interference is eliminated by glycoletherdiamine-N, N, N', N'-tetraacetic acid.[3],[4],[5] The colour produced is measured at 520/800 nm and is proportional to the Mg concentration.



Serum gamma-glutamyl transferases[5]

In this enzymatic rate method, the GGT catalyses the transfer of a gamma-glutamyl group from the colorless substrate, gamma-glutamyl p-nitroaniline, to the acceptor, glycylglycine with the production of the coloured product, p-nitroaniline. The system monitors the rate of change in absorbance at 410 nm over a fixed time interval. The rate of change in absorbance is directly proportional to the activity of GGT in a sample.

Serum total protein[6]

When serum is treated with biuret reagent, the peptide bonds of proteins react with cupric ions in alkaline medium to form a violet coloured copper co-ordinate complex. The absorbance of this complex is measured at 540 nm using green filter. The intensity of the colour formed is directly proportional to the amount of proteins present in the sample.



Serum albumin[7]

The method is based on the specific binding of bromocresol green (BCG), an anionic dye, and the protein at acid pH produce a color change of the indicator from yellow–green to green–blue with the resulting shift in the absorption wavelength of the complex. The intensity of the colour formed is proportional to the concentration of albumin in the sample.



Statistical analysis

Statistical analysis was done by applying Pearson's correlation. The data were expressed as mean + standard error. SPSS version 21 (SPSS version 21, IBM SPSS Inc, Chicago, USA) was used for the statistical analysis.


  Results Top


There was significant difference between the mean values of cases and controls in Mg, GGT, AST, ALT, ALP and albumin (P < 0.05), but no significant difference was found between total proteins in cases and controls, as shown in [Table 1]. Pearson correlation coefficient was significant between Mg and GGT in cases, as shown in [Table 2]. Correlation between Mg and GGT is a positive correlation.
Table 1: P value, mean and standard deviations of cases and controls

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Table 2: Correlation between parameters

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  Discussion Top


In the present study, our aim was to study the role of Mg and GGT in ALD. We observed significant decrease in mean of Mg levels and increase in mean of gamma-glutamyl levels in cases of ALD as compared to control [Table 1].

The diagnosis of ALD is quite challenging as there is no single laboratory test or single imaging study that can diagnose it. The diagnosis depends upon the couple of laboratory tests, clinical features and history of patient. The metabolism of alcohol majorly occurs in liver, so liver function tests are mostly deranged in ALD. All investigations of hepatic panel namely serum transaminases, serum protein, serum albumin, serum GGT are affected. Increased transaminase levels are highly suggestive of ALD.[8],[9],[10]

Serum GGT is widely used index in ALD.[11],[12],[13]

However, its elevated levels are sensitive but less specific for alcohol abuse as GGT is elevated in all forms of liver disease.[14],[15] Teschke et al. in their research study “ALD associated with the increased GGT activities in serum and liver” observed that the increased GGT activities commonly found in ALD can be ascribed primarily to hepatic enzyme induction rather than to liver cell injury, since hepatic GGT activities were increased but not reduced.[3]

Mg is required at micromolar concentrations as an essential co-factor for many fundamental biological processes, especially enzymatic reactions involving energy metabolism, nucleic acid synthesis, immunoglobin synthesis, immune cell adherence, antibody-dependent cytolysis and GM lymphocyte binding.[16],[17],[18]

The factors that cause hypomagnesaemia in ALD are as follows:

  • Poor absorption of Mg in distal jejunum[2]
  • Administration of magnesiuric diuretics like furosemide[19]
  • Decreased plasma level of albumin.[20],[21],[22],[23]


This study's findings are in conformity with Liu et al. in their review article “Mg and liver disease” which concluded that Mg status is closely linked with liver function. Liver diseases have a significant effect on body Mg content, and Mg levels in turn influence the disease processes.[2] Conversely, Mg deficiency aggravates cirrhosis and ALD and can cause liver cancer progression, due to disrupted mitochondrial function.

Other research data also supports this study. Gandhi et al. in “A study on changes in serum GGT and Mg level in ALD”[24] and Cara Torruellas, Samuel W French in “Diagnosis of ALD”[25] concluded that serum Mg can also be used as a marker of chronic ALD along with serum GGT as they have significant correlation in ALD.


  Conclusion Top


There is significant correlation between GGT and Mg in ALD. Routine assessment of Mg along with other tests in hepatic panel should be considered. Mg can also be further used as a micronutrient in the management of ALD.

Limitations

Clinical trials are needed to establish the relation.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
O'Shea RS, Dasarathy S, McCullough AJ. Alcoholic liver disease: AASLD Practice Guidelines (PDF). Hepatology 2010;51:307-28.  Back to cited text no. 1
    
2.
Liu M, Yang H, Mao Y. Magnesium and liver disease. Ann Transl Med 2019;7:578.  Back to cited text no. 2
    
3.
Teschke R, Rauen J, Neuefeind M, Petrides AS, Strohmeyer G. Alcoholic liver disease associated with increased gamma-glutamyl transferase activities in serum and liver. Adv Exp Med Biol 1980;132:647-54.  Back to cited text no. 3
    
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Abernethy MH, Fowler RT. Micellar improvement of the calmagite compleximetric measurement of magnesium in plasma. Clin Chem 1982;28:520-2.  Back to cited text no. 4
    
5.
Committee of Enzymes of the Scandinavian Society for Clinical Chemistry and Clinical Physiology. A recommended method for the determination of gamma-glutamyltransferase in blood Scand J Clin Lab Invest 1976;36:119-25.  Back to cited text no. 5
    
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Henry RJ, Cannon DC, Winkelman JW. Clinical chemistry, Principles and Techniquies. 2nd ed. New York: Harper & Row; 1974.  Back to cited text no. 6
    
7.
Wolf RL. Methods and Techniques in Clinical Chemistry. N.Y: Willey Interscience; 1972.  Back to cited text no. 7
    
8.
Yersin B, Nicolet JF, Dercrey H, Burnier M, van Melle G, Pécoud A. Screening for excessive alcohol drinking. Comparative value of carbohydrate-deficient transferrin, gamma-glutamyltransferase, and mean corpuscular volume. Arch Intern Med 1995;155:1907-11.  Back to cited text no. 8
    
9.
Conigrave KM, Degenhardt LJ, Whitfield JB, Saunders JB, Helander A, Tabakoff B, et al. CDT, GGT, and AST as markers of alcohol use: The WHO/ISBRA collaborative project. Alcohol Clin Exp Res 2002;26:332-9.  Back to cited text no. 9
    
10.
Rosman AS, Lieber CS. Diagnostic utility of laboratory tests in alcoholic liver disease. Clin Chem 1994;40:1641-51.  Back to cited text no. 10
    
11.
Salaspuro M. Conventional and coming laboratory markers of alcoholism and heavy drinking. Alcohol Clin Exp Res 1986;10:5S-12S.  Back to cited text no. 11
    
12.
Conigrave KM, Davies P, Haber P, Whitfield JB. Traditional markers of excessive alcohol use. Addiction 2003;98 Suppl 2:31-43.  Back to cited text no. 12
    
13.
Hietala J, Puukka K, Koivisto H, Anttila P, Niemelä O. Serum gamma-glutamyl transferase in alcoholics, moderate drinkers and abstainers: Effect on gt reference intervals at population level. Alcohol Alcohol 2005;40:511-4.  Back to cited text no. 13
    
14.
Sillanaukee P, Massot N, Jousilahti P. Dose response of laboratory markers to alcohol consumption in a general population. Am J Epidemiol 2000;152:747-51.  Back to cited text no. 14
    
15.
Reynaud M, Schellenberg F, Loisequx-Meunier MN, Schwan R, Maradeix B, Planche F, et al. Objective diagnosis of alcohol abuse: Compared values of carbohydrate-deficient transferrin (CDT), gamma-glutamyl transferase (GGT), and mean corpuscular volume (MCV). Alcohol Clin Exp Res 2000;24:1414-9.  Back to cited text no. 15
    
16.
Swaminathan R. Magnesium metabolism and its disorders. Clin Biochem Rev 2003;24:47-66.  Back to cited text no. 16
    
17.
Saris NE, Mervaala E, Karppanen H, Khawaja JA, Lewenstam A. Magnesium. An update on physiological, clinical and analytical aspects. Clin Chim Acta 2000;294:1-26.  Back to cited text no. 17
    
18.
Galland L. Magnesium and immune function: An overview. Magnesium 1988;7:290-9.  Back to cited text no. 18
    
19.
Ryan MP, Devane J, Ryan MF, Counihan TB. Effects of diuretics on the renal handling of magnesium. Drugs 1984;28 Suppl 1:167-81.  Back to cited text no. 19
    
20.
Kalbfleisch JM, Lindeman RD, EarlGinn H, Smith WO. Effects of ethanol administration on urinary excretion of magnesium and other electrolytes in alcoholic and normal subject. J Clin Invest 1963;42:1471-5.  Back to cited text no. 20
    
21.
Koivisto M, Valta P, Höckerstedt K, Lindgren L. Magnesium depletion in chronic terminal liver cirrhosis. Clin Transplant 2002;16:325-8.  Back to cited text no. 21
    
22.
McCollister RJ, Prasad AS, Doe RP, Flink EB. Normal renal magnesium clearance and the effect of water loading, chlorothiazide, and ethanol on magnesium excretion (abstract). J Lab Clin Med 1958;52:928.  Back to cited text no. 22
    
23.
Heaton FW, Pyrah LN, Beresford CC, Bryson RW, Martin DF. Hypomagnesaemia in chronic alcoholism. Lancet 1962;2:802.  Back to cited text no. 23
    
24.
Gandhi PA, Sendhav SS, Sanghani HI, Patel AP. A study on changes in serum GGT and magnesium level in alcoholic liver disease. Int J Med Res Health Sci 2014;3:12.  Back to cited text no. 24
    
25.
Torruellas C, French SW. Diagnosis of alcoholic liver disease. World J Gastroenterol 2014;20:11684-99.  Back to cited text no. 25
    



 
 
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