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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
ORIGINAL ARTICLE  
Year : 2019  |  Volume : 30  |  Issue : 5  |  Page : 1032-1037
Effects and association of pro-oxidants with magnesium in patients with diabetic nephropathy


1 Department of Biochemistry, Government Medical College, Datia, Madhya Pradesh, India
2 Department of Biochemistry, Saraswathi Institute of Medical Sciences, Hapur, Uttar Pradesh, India
3 Department of Anatomy, GSL Medical College, Rajahmundry, Andhra Pradesh, India
4 Department of Pharmacology, GSL Medical College, Rajahmundry, Andhra Pradesh, India
5 Department of Biochemistry, Mahatma Gandhi Memorial Medical College, Indore, Madhya Pradesh, India

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Date of Submission12-Sep-2018
Date of Decision28-Oct-2018
Date of Acceptance29-Oct-2018
Date of Web Publication4-Nov-2019
 

   Abstract 


Diabetic nephropathy (DN) is the most common microvascular complication observed in patients with type-2 diabetes mellitus. Furthermore, magnesium (Mg) deficiency is a common problem in diabetic patients. In this study, we estimated the levels of Mg, which is an important trace element and pro-oxidant marker, and then evaluated the association between serum Mg and pro-oxidants in patients with DN. In the present study, 200 patients were enrolled and were divided into two groups. The control and DN groups consisted of 100 healthy individuals and 100 patients with DN, respectively. Serum Mg, total anti-oxidant capacity (TAC), and superoxide dismutase (SOD) levels were estimated using the Calmagite, Koracevic, and Marklund and Marklund methods, respectively. Glutathione (GSH) and malondialdehyde (MDA) levels were estimated using the Tietze F and Jean CD method, respectively. Mg levels were found to be significantly decreased in the DN group in comparison to the control group. Anti-oxidant markers were statistically significantly reduced (P <0.001), whereas MDA levels were statistically significantly elevated (P <0.001) in the DN group compared to the control group. There was a significant positive association of Mg with TAC, SOD, and GSH. A statistically significant negative association of Mg with MDA (r = −0.302, P <0.001, n = 100) was also observed. An apparent relationship was observed between hypomagnesemia and oxidative stress in patients with DN. Lower levels of Mg and oxidative stress were also strongly linked.

How to cite this article:
Kachhawa K, Kachhawa P, Agrawal D, Kumar S, Sarkar PD. Effects and association of pro-oxidants with magnesium in patients with diabetic nephropathy. Saudi J Kidney Dis Transpl 2019;30:1032-7

How to cite this URL:
Kachhawa K, Kachhawa P, Agrawal D, Kumar S, Sarkar PD. Effects and association of pro-oxidants with magnesium in patients with diabetic nephropathy. Saudi J Kidney Dis Transpl [serial online] 2019 [cited 2019 Nov 21];30:1032-7. Available from: http://www.sjkdt.org/text.asp?2019/30/5/1032/270257



   Introduction Top


Diabetic nephropathy (DN) is the most common cause of microvascular complications observed in patients with type-2 diabetes mellitus (T2DM).[1] DN is a progressive disease that takes a long time to develop. Primary symptoms of DN include increased excretion of urinary albumin and glomerular hyperfiltration.[2] In this study, we estimated the levels of magnesium (Mg), an important trace element and a pro-oxidant marker, total antioxidant capacity (TAC), superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH) and then evaluated their association in patients with DN. Mg is a chief electrolyte of physiological importance; it is one of the most important intracellular cations in the cells.[3] Significant changes in Mg levels can be observed in patients with DN. An increased prevalence of Mg deficiency has been identified in patients with DN, especially in those who have poorly controlled glycemic profiles, with longer duration of the disease, and with the presence of chronic micro-vascular complications.[4] However, the antioxidant defense system of the body reduces damage by decreasing oxidative stress.[5] The most common cause is diabetes or hyperglycemia, which increases the production of reactive oxygen species (ROS), causing cellular dysfunction and damage, ultimately resulting in diabetic microvascular complications.


   Materials and Methods Top


The study was performed in the Biochemistry Department at the Sri Aurobindo Institute of Medical Sciences (SAIMS) and Hospital. The present study included a total of 200 patients, divided into two groups. The control group consisted of 100 healthy individuals, and the DN group consisted of 100 patients with DN. The patients were diagnosed to have DN in the Department of Nephrology at the SAIMS Hospital. They were selected randomly without any bias for age, sex, occupation, socioeconomic status, and duration of disease. The period of study was from January 2015 to November 2016.

Ethical statement

The proposal of the study was presented to the Institutional Ethics Committee after the pilot project was successful. The study was approved by the ethical committee of the SAIMS institute. Informed consent was obtained from all patients. There was no active intervention in the treatment protocol of the patients. The principles of Helsinki declaration were strictly adhered to during the entire course of the study.

Inclusion criteria

All patients with DN diagnosed by the Department of Nephrology at SAIMS Hospital in whom consent was obtained for this study and patients with a positive dipstick test for microalbuminuria were included in the study.

Exclusion criteria

All patients with macroalbuminuria, patients on dialysis, and patients suffering from other medical conditions, such as cardiac disease, were excluded.

Blood samples were taken from the antecubital vein following overnight fasting. The blood sample was collected in plain, fluoride, and EDTA-coated vacutainers. The blood sample was centrifuged for 15 min at 3000 rpm at room temperature. The serum was stored at 4°C for biochemical investigations.[6] Serum Mg was estimated by the Calmagite method.[7] TAC was estimated with the D. Koracevic method.[8] SOD was estimated using the Marklund and Marklund method.[9] GSH content in red blood cells was estimated with the Tietze F method.[10] MDA was estimated with the Jean CD method.[11]


   Statistical Analysis Top


Statistical analysis was performed using the Statistical Package for Social Sciences version 21.0 (IBM Corp., Armonk, NY, USA). Results were expressed as mean ± standard deviation and were analyzed by unpaired Student’s t-test. Pearson’s correlation was used to evaluate the correlations between the variables of the case groups, and significance was set at P >0.05.[9],[10],[11]


   Results Top


The study included 100 healthy controls and 100 patients with DN, matched for age and sex. Both groups underwent complete history and clinical examination. Demographic data, fasting blood sugar (FBS) level, basal metabolic index (BMI), Mg levels, and stress profile examination of both case and control groups are presented in [Table 1]. BMI and FBS statistically significantly increased (P <0.001) in cases compared to the control group. Mg levels statistically significantly decreased (P <0.001) in cases compared to the control group. Anti-oxidant markers (TAC, SOD, and GSH) statistically significantly decreased (P <0.001), and MDA levels significantly increased in cases compared to those in the control group.
Table 1: Demographic parameters, trace elements, and anti-oxidant profile in case and control groups (mean ± standard deviation).

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[Table 2] shows the correlation analyses between Mg and the different variables that are depicted in [Figure 1], [Figure 2], [Figure 3], [Figure 4]. [Figure 1], [Figure 2], and [Figure 4] show a significant positive association of Mg with TAC (r = 0.501, P <0.001, n = 100), SOD (r = 0.287, P<0.001, n = 100), and GSH (r = 0.539, P <0.001, n = 100), respectively. [Figure 3] shows a statistically significant negative association of Mg with MDA (r = −0.302, P <0.001, n = 100).
Table 2: Association of magnesium levels with pro-oxidant parameters in cases.

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Figure 1: Correlation between serum magnesium and total anti-oxidant capacity.

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Figure 2: Correlation between serum magnesium and super oxide dismutase.

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Figure 3: Correlation between serum magnesium and malondialdehyde.

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Figure 4: Correlation between serum magnesium and glutathione.

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   Discussion Top


In this study, we found a significant lower level of serum Mg in cases than in the control group. Several other studies have also reported similar results in patients with DN.[12],[13],[14] Mg is an intracellular cation and affects several metabolic pathways of glucose utilization.[15] However, the precise mechanism of serum Mg deficiency is not completely known. The mechanism of Mg deficiency, which is directly associated with a depletion of Mg, is based on their utilization. One accepted mechanism based on increased urinary excretion of Mg has been hypothesized to be a result of osmotic diuresis, suggesting an association between diabetes with low Mg levels. Some other important factors include diarrhea, vomiting, and poor sodium intake, which can lead to Mg deficiency in DN patients.[16] Hyperglycemia and insulinemia also increase urinary Mg excretion. Urinary Mg excretion and FBS have been found to be inversely related to serum Mg levels.[17] Hypo-magnesemia is currently considered to be an accurate predictor of progression of DN.[18],[19] Furthermore, a previous study has also demonstrated an inverse relation between Mg intake and DM.[20]

Mg deficiency leads to the activation of the renin–angiotensin system, which also induces oxidative stress.[21] Other studies have also shown that hyperglycemia induced free radical formation, inflammation, apoptosis, and cell death, resulting in compromised anti-oxidant function.[22] In this study, we found a significant correlation between serum Mg and antioxidant profile. TAC, SOD, and GSH have been shown to have a significant positive correlation with Mg, consistent with previous studies.[23] Mechanisms contributing to the formation of free radicals in T2DM may include nonenzymatic and auto-oxidative glycosylation, the inflammatory mediators, and a weak anti-oxidant defense system.[23] However, Mg itself has been reported to possess anti-oxidant properties by scavenging free radicals, probably by affecting the rate of spontaneous oxidation and reduction of superoxide anion.[23],[24] Mg is helpful in the maintenance of GSH concentration to protect against damage due to free radicals in the erythrocyte membrane. Thus, GSH deficiency may impair the activity of antioxidant enzymes as well as chain-breaking aqueous and lipid phase antioxidants in the cell wall. A previous study has also established a strong, direct correlation between Mg levels in red blood cells and circulating reduced/oxidized glutathione concentration (r = 0.84, P <0.0001).[25] Some studies have also found a negative correlation between Mg levels and oxidative stress markers (SOD and MDA) in patients that were chronically exposed to stress.[26] However, similar studies in Korean adults reported no such correlation, which was incon-sistent with our results.[27]

MDA is a by-product formed by lipid peroxidation of cellular polyunsaturated fatty acids. MDA formation is thought to play an important role in the development of late diabetic complications.[28],[29] Erythrocytes from Mg-deficient animals are more susceptible to damage from free radicals. In our study, plasma MDA negatively correlated with serum Mg level, which was indicative of the role of Mg in the generation of ROS, thereby causing lipid per-oxidation. A previous study has also shown a negative correlation between Mg and MDA.[29],[30] Furthermore, hypo-magnesemia is currently considered an accurate predictor of progression of DN.


   Conclusion Top


Our study demonstrates an apparent relationship between hypo-magnesemia and oxidative stress in patients with DN. Lower levels of Mg and oxidative stress were strongly linked. The results of this study may also be helpful in the formulation of effective antioxidant therapies for patients with early development of DN and better management of the disease. Consequently, we propose that a better understanding of Mg metabolism and effort to minimize hypomagnesemia and stress in the management of patients with diabetes mellitus is required. Therefore, further pre-clinical and clinical studies are necessary to clarify the mechanisms involved in the relationship between Mg deficiency, oxidative stress, and associated complications.

Conflict of interest: None declared.



 
   References Top

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Varma M, Kachhawa K, Sahu A, Kachhawa P. Association of antioxidant enzymes and MDA level in diabetic nephropathy patients in Indore region of Madhya Pradesh. J Pure Appi Microbiol 2014;8:4137-41.  Back to cited text no. 30
    

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Correspondence Address:
Sanjay Kumar
Department of Pharmacology, GSL Medical College, Rajahmundry, Andhra Pradesh
India
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DOI: 10.4103/1319-2442.270257

PMID: 31696840

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