Protective effect of magnesium on renal function in STZ-induced diabetic rats
© Parvizi et al.; licensee BioMed Central Ltd. 2014
Received: 15 January 2014
Accepted: 23 July 2014
Published: 16 August 2014
Diabetic nephropathy is a serious complication of T1D (type one diabetes mellitus). Persistent hyperglycemia and subsequent hypomagnesemia is believed to develop kidney damage by activation of oxidative stress. We conducted this study to investigate the renoprotective effect of magnesium sulfate (MgSO4) on renal histopathology and oxidative stress in diabetic rats.
The study included 70 male rats. The animals were divided into seven groups: control (CRL), control receiving MgSO4 (CRL + Mg1 & CRL + Mg8), diabetic (DM1 & DM8) and diabetic receiving MgSO4 (DM + Mg1 & DM + Mg8). Rats were given 20 mg/kg (i.p) Streptozocin (STZ) for 5 consecutive days in (MLD) multiple low doses to induce T1D. At day 10 treatment groups were received MgSO4 (10 g/l) in drinking water, for 1 or 8 weeks. The blood glucose, BUN and creatinine levels were measured. Renal tissue levels of malondialdehyde (MDA) were measured by thiobarbituric acid (TBA) method to evaluate the oxidative stress. Renal histopathology was done using H & E staining method.
Treatment with MgSO4 significantly decreased the blood glucose in DM + Mg1 and DM + Mg8 groups as compared with DM1 and DM8. Magnesium treatment also decreased serum BUN and tissue level of MDA significantly in both short and long term treatment. The body weight loss and kidney weight to body weight ratio was improved by MgSO4. Histological results showed there were no differences between DM and DM + Mg groups.
Our findings showed that diabetic nephropathy is associated with high blood glucose level and oxidative stress (significant increase in MDA level). The renal dysfunction and oxidative stress can be improved by magnesium sulfate administration. It is suggested that protection against development of diabetic nephropathy by MgSO4 treatment involves changes in the blood glucose and oxidative stress.
KeywordsDiabetes mellitus type 1 Streptozocin Diabetic nephropathy Oxidative stress
Diabetic nephropathy is a major long-term complication of Type 1 diabetes mellitus (T1D) -. It develops in more than of 40% of patients in spite of glucose control . Oxidative stress has been considered to be a pathogenic factor for diabetic nephropathy . Hyperglycemia is believed to activate oxidative stress resulting in proteinuria, basement membrane thickening, expansion of the mesangium, decline in filtration and nephromegaly followed by glomerular sclerosis ,. It is suggested that increased oxidative stress through reduction of plasma antioxidants and increased lipid peroxidation could intensify mesangial cells susceptibility to free radical injury ,. Malondialdehyde (MDA) is a substance produced during polyunsaturated fatty acid peroxidation which has been detected in the serum of patients with T1D and correlate with the progression of disease -. MDA is known to have toxic influence on cell membrane structure. It can modulate signal transduction as well as modify proteins and DNA .
Magnesium (Mg) has received important attention for its potential in improving diabetes and its complications . Mg deficiency has previously been proposed as a prominent factor leading to the pathogenesis of the diabetes complications . Hypomagnesemia has been implicated in the development of diabetic complications due to enhanced renal Mg excretion ,,. The study of Prabodh suggested that hypomagnesemia may be related to development of diabetic nephropathy . Hypomagnesemia was found to be related to weak glycemic control and increased incidence of nephropathy and retinopathy . The study of Srivastava indicated that MgSO4 can improve oxidative stress by decreasing MDA generation in sodium-metavanadate induced lipid peroxidation . However, the possibility that MgSO4 could exert beneficial effects in improving diabetic renal damage has not been previously investigated. It seems that Mg as magnesium sulfate (MgSO4) will be able to effectively limit oxidative stress. Thus this study was conducted to evaluate the renoprotective and antioxidant effects of oral magnesium administration on STZ- Induced diabetic rats in short and long term periods.
Materials and methods
Male Wistar rats, weighing 200 ± 20 g were used. Animals were kept at a constant temperature of 22 ± 2°C with fixed 12:12-h light-dark cycle. Animals were divided into seven groups (n = 10): Control (CRL), control treated by magnesium sulfate for one week (CRL + Mg1), control treated by magnesium sulfate for 8 weeks (CRL + Mg8), untreated diabetic for one week (DM1), untreated diabetic for 8 weeks (DM8), diabetic treated by magnesium sulfate for one week (DM + Mg1) and diabetic treated by magnesium sulfate for 8 weeks (DM + Mg8). All the experiments were approved by the Ethics committee of Tehran University of Medical Sciences (Tehran, Iran).
Diabetes were induced by intraperitoneal (i.p) injection of multiple low doses (20 mg/kg) of STZ (Sigma-Aldrich Inc., USA) for 5 consecutive days . In 10th days, the blood glucose levels were determined using a glucometer (ACCU-CHEK Active, Germany) and animals with blood glucose levels above 250 mg/dl were considered to be diabetic . Control rats were injected with the same volume of vehicle. Mg-treated rats were received 10 g/l of MgSO4 added to the drinking water from 10th days . Untreated groups of STZ- diabetic and control rats were given drinking water over the same period.
Blood sampling and biochemical assay
Blood samples were taken for glucose, creatinine, BUN, calcium and Mg levels measurements using a kit (Zistshimi, Tehran, Iran) and spectrophotometer (UV 3100, Shimadzu). Blood samples were centrifuged at 2000 g for 10 minutes at 4°C, and serums were used for biochemical assay. All analysis was performed in accordance with the instructions provided by the manufacturers. Serum creatinine concentration was determined using Jaffe method  and BUN was determined using UV method by autoanalyzer (BT 3000).
At the end of experiment, rats were euthanized with high-dose of ketamine. The right kidney of the animals in all groups were identified, resected, dried by tissue papers and weighed by digital scale on Sartorius balance to determine the change in the weight of organs with respect to their body weights. A change in kidney size was estimated by division the weight of the right kidney to total body weight . The kidney was removed from each rat, put into 10% formalin and embedded in paraffin. Each sample was then cut into 5-µ m sections with a microtome and deparaffined with xylene. Then sections are subjected to standard hematoxylin/eosin staining. The sections were observed under a light microscope at magnifications of 400x -. Determination of MDA in lipid peroxidation study was performed by thiobarbituric acid (TBA) method . Briefly, the renal tissue was mixed with 2 volumes of 10% trichloroacetic acid (TCA) for protein precipitating. After centrifugation of the precipitate, supernatant is separated and reacted with TBA in boiling water for 10 min followed by cooling. The concentration of MDA was measured at 532 n m ,.
Results were expressed as mean ± SEM. Differences among groups were evaluated by one- way analysis of variance (ANOVA) with Tukey post-hoc test. Statistical significance was achieved if the p < 0.05.
Effects of magnesium sulfate administration on blood glucose
Change in body weight and kidney weight/body weight (KW/BW) ratio
Effects of magnesium sulfate administration on plasma level of Mg2+
Effects of magnesium sulfate administration on plasma level of BUN and creatinine
Effects of magnesium sulfate treatment on MDA level in renal tissue
Diabetes mellitus can cause serious health problems including macrovascular and microvascular complications such as kidney failure, heart disease, stroke and etc., which affects the function of many organs . One of them is injuries to the kidney tissue that results in renal dysfunction . This study was designed to evaluate the renal complication of T1D in short and long term and probable protective effects of MgSO4. We used the multiple low doses of STZ to induce T1D in rats according to previous reports ,. Eight weeks after STZ-diabetes induction, some indexes of renal damage such as increasing BUN and elevation of renal MDA were appeared. Magnesium treatment could reverse renal function (decreasing BUN), decreasing MDA and improving hyperglycemia and kidney weight respect to body weight in diabetic rats.
Previous studies has been proved that treatment with MgSO4 have beneficial effects on diabetes. It could improve some of diabetic complications such as hypertension ,, thermal hyperalgesia and structure of pancreatic islets ,. Also MgSO4 improves function of endothelium and restores hemodynamic and tubular function in postischemic rats . With respect of soltani study , we used magnesium supplementation (10 g/l) via drinking water to diabetic rats from 10th days after diabetes induction for short time (one week) or long time (eight weeks).
Our results showed that consumption of MgSO4 in diabetic rats reversed the high blood glucose level. However, MgSO4 couldn’t return it to that control levels in the treated diabetic rats. Magnesium plays an important role in the carbohydrate metabolism regulation . We have been previously showed that treatment by MgSO4 could reduce the blood glucose in diabetic rats . The effect of MgSO4 on blood sugar levels may be related to the fact that it is a crucial cofactor for glucose transport and various enzymes involved in carbohydrate metabolism . It has also been reported that oral MgSO4 consumption in male obese rats improved glucose tolerance and delaying the progression of diabetes . It is supposed that blood glucose levels can be decreased by Mg via increasing GLUT4 mRNA expression in diabetic rats independent to insulin secretion . Huang et al. showed that MgSO4 increases the expression of GLUT3 in the cortex and hippocampus of gerbil brains .
We showed that after one week MgSO4 treatment (in drinking water), the plasma Mg levels in both DM1 and DM + Mg1 groups didn’t show any significant changes in comparison with control group. In previous work, Soltani et al., showed that a significant reduction in Mg level in acute diabetic groups . These discrepancy may be due to the dose of STZ and the model of diabetes induction. Because in this study we used MLD injection of STZ, but in the Soltani et al., study they used single high dose of STZ for diabetes induction . In other hand, after few days following diabetes induction, rats showed polydipsia and polyuria along with diarrhea (in DM + Mg groups). Actually, in long term diabetes, ingestion of water and meal, reached near to control rats. It may be due to adaptation.
High Magnesium (as MgSO4) ingestion has been reported to induce diarrhea. In short term diabetes, diarrhea and polyuria along with polydipsia can cause non-significant changes in magnesium level ,.
Our results showed that Mg administration to DM + Mg8, after eight weeks, could decrease the level of renal function markers such as BUN and creatinine in comparison to DM8. An elevation of BUN in DM8 groups may reflect decreasing in glomerular filtration rate (GFR) or it is probably due to increased degradation of proteins . Avram et al., showed that there is a negative correlation between renal size and serum creatinine level . So in our study, mildly elevation of creatinine may be associated with renomegaly as shown in this study.
Increasing BUN and plasma creatinine, has been reported as waste products of metabolism following kidney injury and they has known biomarkers of kidney degeneration . In this study, the elevation of plasma BUN with hyperglycemia can be proposed as indicator for renal dysfunction . Our data showed no significant changes in the creatinine level in diabetic animals versus CRL group. Increase in creatinine level occurs at the end stage of renal disease, and this is accompanied by histological alterations . Kim et al., suggested that plasma BUN and creatinine is often measures together, but former is more sensitive marker for kidney injury .
Histological study also showed that there were no profound changes among the experimental groups. Eight weeks after induction of diabetes in DM8 groups’ tissue didn’t changes histologically. It seems that it requires long time to cause an end stage renal disease with changes in creatinine level and histological changes. In previous study, it has been shown that it take about 15 weeks to see profound histological changes . So it may be due to insufficient time that we didn’t see this changes.
Diabetes induction resulted in an increase in kidney MDA, which is an indicator of oxidative stress. Israa et al., revealed that enhancement of the oxidative stress as indicated by high MDA level is due to increase in blood glucose . Metabolically, diabetes is characterized by diminished glucose utilization and increased lipid peroxidation, resulting in accumulation of MDA in renal tissue. The elevated level of MDA may be due to the poor antioxidant capacity of mesangial cells as a result of low glutathione (GSH) levels . Evidences showed that in patients with T2D, the higher levels of lipid peroxidation and hypomagnesaemia are often reported . Free radicals in DM cause peroxidative breakdown of phospholipids that lead to accumulation of MDA . Agnieszka et al., have been shown that magnesium intake for 18 weeks could prevent lipid peroxidation stimulated by vanadium in hepatic tissue . Thus, from our results it is seemed that magnesium may show an antioxidant activity through preventing lipid peroxidation in renal tissue that is indicated by a decrease in kidney MDA level. Ribeiro et al., demonstrated a negative correlation between magnesium and glucose levels as well as between magnesium and oxidative stress . Magnesium deficiency enhances oxidative stress by increased production of free radicals and decreased of antioxidant defenses . In this regard, histological alterations can be due to mildly proinflammatory invasion to renal tissues.
Hyperglycemia induces diabetic nephropathy via several biochemical pathways. Several mechanisms have revealed to depict the adverse effect of hyperglycemia, including protein kinase C (PKC) , mitogen-activated protein kinase (MAPK), polyol pathway, advanced glycation end products (AGE), aldose reductase activation  and oxidative stress . In the other hand, it has been reported that hypomagnesemia is a novel predictor of end stage renal disease (ESRD) in patients with type 2 diabetic nephropathy . So it is suggested that oxidative stress causing damage to mesangial cells and magnesium could reduce oxidative damages to mesangial cells as indicated by decreasing MDA production.
In addition, we assessed the effects of magnesium administration on the body weight and kidney weight to body weight ratio in diabetic rats. We found that induction of diabetes caused body weight loss. Decrease in body weight following STZ-induced diabetes notably in eight weeks groups, may be due to degradation of proteins as indicated by raising serum BUN and creatinine levels. Area under curve showed that in DM + Mg groups, Mg treatment caused body weight gain, especially in DM + Mg8 groups.
Also our results showed that KW/BW ratio was significantly elevated in untreated diabetic rats and decreased in DM + Mg groups. KW/BW ratio is a marker of renomegaly , its increment is an indicator of glumerolar expansion due to diabetes. Several investigators have reported that KW/BW increases in DM animals . Renet et al., showed that marked increase in the KW/BW, tubulointerstitial fibrosis and fibronectin in STZ-induced diabetic rats from 8 to 16 weeks . Arozal et al., oxidative stress is associated with development of hypertrophy in diabetes . Sharma et al., revealed that renal hypertrophy in T1D was related to overexpression of TGF-β1 in the glomerular mesangial cells . Our study further strengthens the notion that attenuation of kidney weight by magnesium, suggesting that Mg has the ability to protect the kidneys from oxidative injury. It may reverse kidney hypertrophy in STZ-diabetic rats.
Limitations of this study was to evaluate more precisely the oxidant and antioxidant markers for achieving better results, because of limitation in financial support. We haven’t access to electron microscope for more precise evaluation of histological changes.
The current study determined that the increase in blood glucose level is related to the development of oxidative stress as indicated by high MDA level. Control of hyperglycemia by Mg supplementation can decreases oxidative damages as indicated by MDA and improves renal dysfunction via lowering of BUN and creatinine. However, further studies are required to clear the precise mechanism(s) involving for the protective effect of MgSO4 against the diabetic nephropathy in experimental conditions.
This research was supported by Tehran University of Medical Sciences, Tehran, Iran.
- Lu HJ, Tzeng TF, Hsu JC, Kuo SH, Chang CH, Huang SY, Chang FY, Wu MC, Liu IM: An aqueous-ethanol extract of liriope spicata var. prolifera ameliorates diabetic nephropathy through suppression of renal inflammation. Evid Based Complement Alternat Med 2013, 2013: 201643. Epub 2013/09/13PubMedPubMed CentralGoogle Scholar
- Schena FP, Gesualdo L: Pathogenetic mechanisms of diabetic nephropathy. J Am Soc Nephrol 2005, 16(Suppl 1):S30-S33. Epub 2005/06/07 10.1681/ASN.2004110970View ArticlePubMedGoogle Scholar
- Ribeiro MC, Avila DS, Barbosa NB, Meinerz DF, Waczuk EP, Hassan W, Rocha JB: Hydrochlorothiazide and high-fat diets reduce plasma magnesium levels and increase hepatic oxidative stress in rats. Magnes Res 2013, 26(1):32–40. Epub 2013/05/10PubMedGoogle Scholar
- Gross JL, de Azevedo MJ, Silveiro SP, Canani LH, Caramori ML, Zelmanovitz T: Diabetic nephropathy: diagnosis, prevention, and treatment. Diabetes Care 2005, 28(1):164–176. Epub 2004/12/24 10.2337/diacare.28.1.164View ArticlePubMedGoogle Scholar
- Kumawat M, Sharma TK, Singh I, Singh N, Ghalaut VS, Vardey SK, Shankar V: Antioxidant enzymes and lipid peroxidation in type 2 diabetes mellitus patients with and without nephropathy. N Am J Med Sci 2013, 5(3):213–219. Epub 2013/04/30 10.4103/1947-2714.109193View ArticlePubMedPubMed CentralGoogle Scholar
- Hans CP, Chaudhary DP, Bansal DD: Magnesium deficiency increases oxidative stress in rats. Indian J Exp Biol 2002, 40(11):1275–1279. Epub 2003/09/19PubMedGoogle Scholar
- Walti MK, Zimmermann MB, Spinas GA, Jacob S, Hurrell RF: Dietary magnesium intake in type 2 diabetes. Eur J Clin Nutr 2002, 56(5):409–414. Epub 2002/05/10 10.1038/sj.ejcn.1601327View ArticlePubMedGoogle Scholar
- Del Rio D, Stewart AJ, Pellegrini N: A review of recent studies on malondialdehyde as toxic molecule and biological marker of oxidative stress. Nutr Metab Cardiovasc Dis 2005, 15(4):316–328. Epub 2005/08/02 10.1016/j.numecd.2005.05.003View ArticlePubMedGoogle Scholar
- Uchida K: Lipofuscin-like fluorophores originated from malondialdehyde. Free Radic Res 2006, 40(12):1335–1338. Epub 2006/11/09 10.1080/10715760600902302View ArticlePubMedGoogle Scholar
- Kamper M, Tsimpoukidi O, Chatzigeorgiou A, Lymberi M, Kamper EF: The antioxidant effect of angiotensin II receptor blocker, losartan, in streptozotocin-induced diabetic rats. Transl Res 2010, 156(1):26–36. Epub 2010/07/14 10.1016/j.trsl.2010.05.004View ArticlePubMedGoogle Scholar
- Srivastava S, Chandrasekar B, Bhatnagar A, Prabhu SD: Lipid peroxidation-derived aldehydes and oxidative stress in the failing heart: role of aldose reductase. Am J Physiol Heart Circ Physiol 2002, 283(6):H2612-H2619. Epub 2002/10/22View ArticlePubMedGoogle Scholar
- Li B, Tan Y, Sun W, Fu Y, Miao L, Cai L: The role of zinc in the prevention of diabetic cardiomyopathy and nephropathy. Toxicol Mech Methods 2013, 23(1):27–33. Epub 2012/10/09 10.3109/15376516.2012.735277View ArticlePubMedGoogle Scholar
- Kisters K, Gremmler B, Kozianka J, Hausberg M: Magnesium deficiency and diabetes mellitus. Clin Nephrol 2006, 65(1):77–78. Epub 2006/01/25 10.5414/CNP65077View ArticlePubMedGoogle Scholar
- Sakaguchi Y, Shoji T, Hayashi T, Suzuki A, Shimizu M, Mitsumoto K, Kawabata H, Niihata K, Okada N, Isaka Y, Rakugi H, Tsubakihara Y: Hypomagnesemia in type 2 diabetic nephropathy: a novel predictor of end-stage renal disease. Diabetes Care 2012, 35(7):1591–1597. Epub 2012/04/14 10.2337/dc12-0226View ArticlePubMedPubMed CentralGoogle Scholar
- Prabodh S, Prakash DS, Sudhakar G, Chowdary NV, Desai V, Shekhar R: Status of copper and magnesium levels in diabetic nephropathy cases: a case–control study from South India. Biol Trace Elem Res 2011, 142(1):29–35. Epub 2010/06/17 10.1007/s12011-010-8750-xView ArticlePubMedGoogle Scholar
- Dasgupta A, Sarma D, Saikia UK: Hypomagnesemia in type 2 diabetes mellitus. Indian J Endocrinol Metab 2012, 16(6):1000–1003. Epub 2012/12/12 10.4103/2230-8210.103020View ArticlePubMedPubMed CentralGoogle Scholar
- Scibior A, Golebiowska D, Niedzwiecka I: Magnesium can protect against vanadium-induced lipid peroxidation in the hepatic tissue. Oxid Med Cell Longev 2013, 2013: 802734. Epub 2013/06/15 10.1155/2013/802734View ArticlePubMedPubMed CentralGoogle Scholar
- Maksimovic-Ivanic D, Trajkovic V, Miljkovic DJ, Mostarica Stojkovic M, Stosic-Grujicic S: Down-regulation of multiple low dose streptozotocin-induced diabetes by mycophenolate mofetil. Clin Exp Immunol 2002, 129(2):214–223. Epub 2002/08/08 10.1046/j.1365-2249.2002.02001.xView ArticlePubMedPubMed CentralGoogle Scholar
- Soltani N, Keshavarz M, Sohanaki H, Zahedi Asl S, Dehpour AR: Relaxatory effect of magnesium on mesenteric vascular beds differs from normal and streptozotocin induced diabetic rats. Eur J Pharmacol 2005, 508(1–3):177–181. Epub 2005/02/01 10.1016/j.ejphar.2004.12.003View ArticlePubMedGoogle Scholar
- Soltani N, Keshavarz M, Minaii B, Mirershadi F, Zahedi Asl S, Dehpour AR: Effects of administration of oral magnesium on plasma glucose and pathological changes in the aorta and pancreas of diabetic rats. Clin Exp Pharmacol Physiol 2005, 32(8):604–610. Epub 2005/08/27 10.1111/j.0305-1870.2005.04238.xView ArticlePubMedGoogle Scholar
- Kojima N, Slaughter TN, Paige A, Kato S, Roman RJ, Williams JM: Comparison of the development diabetic induced renal disease in strains of Goto-Kakizaki rats. J Diabetes Metab 2013, Suppl 9(5). Epub 2013/12/10.
- Tesch GH, Allen TJ: Rodent models of streptozotocin-induced diabetic nephropathy. Nephrology (Carlton) 2007, 12(3):261–266. Epub 2007/05/15 10.1111/j.1440-1797.2007.00796.xView ArticleGoogle Scholar
- Cheng MF, Chen LJ, Cheng JT: Decrease of Klotho in the kidney of streptozotocin-induced diabetic rats. J Biomed Biotechnol 2010, 2010: 513853. Epub 2010/07/14 10.1155/2010/513853View ArticlePubMedPubMed CentralGoogle Scholar
- Baig MA, Gawali VB, Patil RR, Naik SR: Protective effect of herbomineral formulation (Dolabi) on early diabetic nephropathy in streptozotocin-induced diabetic rats. J Nat Med 2012, 66(3):500–509. Epub 2011/11/26 10.1007/s11418-011-0614-yView ArticlePubMedGoogle Scholar
- Esterbauer H, Zollner H: Methods for determination of aldehydic lipid peroxidation products. Free Radic Biol Med 1989, 7(2):197–203. Epub 1989/01/01 10.1016/0891-5849(89)90015-4View ArticlePubMedGoogle Scholar
- Esterbauer H, Cheeseman KH: Determination of aldehydic lipid peroxidation products: malonaldehyde and 4-hydroxynonenal. Methods Enzymol 1990, 186: 407–421. Epub 1990/01/01 10.1016/0076-6879(90)86134-HView ArticlePubMedGoogle Scholar
- Esterbauer H, Dieber-Rotheneder M, Waeg G, Puhl H, Tatzber F: Endogenous antioxidants and lipoprotein oxidation. Biochem Soc Trans 1990, 18(6):1059–1061. Epub 1990/12/01View ArticlePubMedGoogle Scholar
- Zafar M, Naeem-ul-Hassan Naqvi S: Effects of STZ-induced diabetes on the relative weights of kidney, liver and pancreas in albino rats: a comparative study. Int J Morphol 2010, 28: 135–142. 10.4067/S0717-95022010000100019View ArticleGoogle Scholar
- Pan HZ, Zhang L, Guo MY, Sui H, Li H, Wu WH, Qu NQ, Liang MH, Chang D: The oxidative stress status in diabetes mellitus and diabetic nephropathy. Acta Diabetol 2010, 47(Suppl 1):71–76. Epub 2009/05/29 10.1007/s00592-009-0128-1View ArticlePubMedGoogle Scholar
- Eid S, Maalouf R, Jaffa AA, Nassif J, Hamdy A, Rashid A, Ziyadeh FN, Eid AA: 20-HETE and EETs in diabetic nephropathy: a novel mechanistic pathway. PLoS One 2013, 8(8):e70029. Epub 2013/08/13 10.1371/journal.pone.0070029View ArticlePubMedPubMed CentralGoogle Scholar
- Cnop M, Welsh N, Jonas JC, Jorns A, Lenzen S, Eizirik DL: Mechanisms of pancreatic beta-cell death in type 1 and type 2 diabetes: many differences, few similarities. Diabetes 2005, 54(Suppl 2):S97-S107. Epub 2005/11/25 10.2337/diabetes.54.suppl_2.S97View ArticlePubMedGoogle Scholar
- Soltani N, Keshavarz M, Sohanaki H, Dehpour AR, Zahedi Asl S: Oral magnesium administration prevents vascular complications in STZ-diabetic rats. Life Sci 2005, 76(13):1455–1464. Epub 2005/02/01 10.1016/j.lfs.2004.07.027View ArticlePubMedGoogle Scholar
- Kim DJ, Xun P, Liu K, Loria C, Yokota K, Jacobs DR Jr, He K: Magnesium intake in relation to systemic inflammation, insulin resistance, and the incidence of diabetes. Diabetes Care 2010, 33(12):2604–2610. Epub 2010/09/03 10.2337/dc10-0994View ArticlePubMedPubMed CentralGoogle Scholar
- de Araujo M, Andrade L, Coimbra TM, Rodrigues AC Jr, Seguro AC: Magnesium supplementation combined with N-acetylcysteine protects against postischemic acute renal failure. J Am Soc Nephrol 2005, 16(11):3339–3349. Epub 2005/09/24 10.1681/ASN.2004100832View ArticlePubMedGoogle Scholar
- Anetor JI, Senjobi A, Ajose OA, Agbedana EO: Decreased serum magnesium and zinc levels: atherogenic implications in type-2 diabetes mellitus in Nigerians. Nutr Health 2002, 16(4):291–300. Epub 2003/03/06 10.1177/026010600201600403View ArticlePubMedGoogle Scholar
- Laires MJ, Monteiro CP, Bicho M: Role of cellular magnesium in health and human disease. Front Biosci 2004, 9: 262–276. Epub 2004/02/10 10.2741/1223View ArticlePubMedGoogle Scholar
- Balon TW, Gu JL, Tokuyama Y, Jasman AP, Nadler JL: Magnesium supplementation reduces development of diabetes in a rat model of spontaneous NIDDM. Am J Physiol 1995, 269(4 Pt 1):E745-E752. Epub 1995/10/01PubMedGoogle Scholar
- Solaimani H, Soltani N, MaleKzadeh K, Sohrabipour S, Zhang N, Nasri S, Wang Q: Modulation of GLUT4 expression by oral administration of Mg (2+) to control sugar levels in STZ-induced diabetic rats. Can J Physiol Pharmacol 2014, 92(6):438–444. Epub 2014/05/14 10.1139/cjpp-2013-0403View ArticlePubMedGoogle Scholar
- Huang CY, Liou YF, Chung SY, Pai PY, Kan CB, Kuo CH, Tsai CH, Tsai FJ, Chen JL, Lin JY: Increased expression of glucose transporter 3 in gerbil brains following magnesium sulfate treatment and focal cerebral ischemic injury. Cell Biochem Funct 2010, 28(4):313–320. Epub 2010/06/03 10.1002/cbf.1659View ArticlePubMedGoogle Scholar
- Laurant P, Touyz RM, Schiffrin EL: Effect of magnesium on vascular tone and reactivity in pressurized mesenteric resistance arteries from spontaneously hypertensive rats. Can J Physiol Pharmacol 1997, 75(4):293–300. Epub 1997/04/01 10.1139/y97-044View ArticlePubMedGoogle Scholar
- Dabla PK: Renal function in diabetic nephropathy. World J Diabetes 2010, 1(2):48–56. Epub 2011/05/04 10.4239/wjd.v1.i2.48View ArticlePubMedPubMed CentralGoogle Scholar
- Avram MM, Hurtado H: Renal size and function in diabetic nephropathy. Nephron 1989, 52(3):259–261. Epub 1989/01/01 10.1159/000185653View ArticlePubMedGoogle Scholar
- Kadkhodaee M, Mikaeili S, Zahmatkesh M, Golab F, Seifi B, Arab HA, Shams S, Mahdavi-Mazdeh M: Alteration of renal functional, oxidative stress and inflammatory indices following hepatic ischemia-reperfusion. Gen Physiol Biophys 2012, 31(2):195–202. Epub 2012/07/12 10.4149/gpb_2012_024View ArticlePubMedGoogle Scholar
- Trujillo J, Chirino YI, Molina-Jijon E, Anderica-Romero AC, Tapia E, Pedraza-Chaverri J: Renoprotective effect of the antioxidant curcumin: Recent findings. Redox Biol 2013, 1(1):448–456. Epub 2013/11/06 10.1016/j.redox.2013.09.003View ArticlePubMedPubMed CentralGoogle Scholar
- Sargin AK, Can B, Turan B: Comparative investigation of kidney mesangial cells from increased oxidative stress-induced diabetic rats by using different microscopy techniques. Mol Cell Biochem 2014, 390(1–2):41–49. Epub 2013 Dec 29 10.1007/s11010-013-1953-7View ArticlePubMedGoogle Scholar
- Kim MJ, Lim Y: Protective effect of short-term genistein supplementation on the early stage in diabetes-induced renal damage. Mediators Inflamm 2013, 2013: 510212. Epub 2013 Apr 29PubMedPubMed CentralGoogle Scholar
- Yokozawa T, Yamabe N, Cho EJ, Nakagawa T, Oowada S: A study on the effects to diabetic nephropathy of Hachimi-jio-gan in rats. Nephron Exp Nephrol 2004, 97(2):e38-e48. Epub 2004/06/26 10.1159/000078405View ArticlePubMedGoogle Scholar
- Israa FJA, Huda Arif J: Role of Antioxidant on Nephropathy in Alloxan Induced Diabetes in Rabbits. Iraqi postgraduate Med J 2009, 8(4):398–402.Google Scholar
- Giannoukakis N, Rudert WA, Trucco M, Robbins PD: Protection of human islets from the effects of interleukin-1beta by adenoviral gene transfer of an Ikappa B repressor. J Biol Chem 2000, 275(47):36509–36513. Epub 2000/09/01 10.1074/jbc.M005943200View ArticlePubMedGoogle Scholar
- Niranjan G, Mohanavalli V, Srinivasan AR, Ramesh R: Serum lipid peroxides and magnesium levels following three months of treatment with pioglitazone in patients with Type 2 Diabetes mellitus. Diabetes Metab Syndr 2013, 7(1):35–37. Epub 2013/03/23 10.1016/j.dsx.2013.02.020View ArticlePubMedGoogle Scholar
- Bhutia Y, Ghosh A, Sherpa ML, Pal R, Mohanta PK: Serum malondialdehyde level: Surrogate stress marker in the Sikkimese diabetics. J Nat Sci Biol Med 2011, 2(1):107–112. Epub 2011/01/01 10.4103/0976-9668.82309View ArticlePubMedPubMed CentralGoogle Scholar
- Scibior A, Gołębiowska D, Niedźwiecka I: Magnesium can protect against vanadium-induced lipid peroxidation in the hepatic tissue. Oxid Med Cell Longev 2013, 2013: 11. 10.1155/2013/802734View ArticleGoogle Scholar
- Agarwal R, Iezhitsa IN, Agarwal P, Spasov AA: Mechanisms of cataractogenesis in the presence of magnesium deficiency. Magnes Res 2013, 26(1):2–8. Epub 2013/05/28PubMedGoogle Scholar
- Dunlop M: Aldose reductase and the role of the polyol pathway in diabetic nephropathy. Kidney Int Suppl 2000, 77: S3-S12. Epub 2000/09/21 10.1046/j.1523-1755.2000.07702.xView ArticlePubMedGoogle Scholar
- Suzuki D, Miyata T, Saotome N, Horie K, Inagi R, Yasuda Y, Uchida K, Izuhara Y, Yagame M, Sakai H, Kurokawa K: Immunohistochemical evidence for an increased oxidative stress and carbonyl modification of proteins in diabetic glomerular lesions. J Am Soc Nephrol 1999, 10(4):822–832. Epub 1999/04/15PubMedGoogle Scholar
- Malatiali S, Francis I, Barac-Nieto M: Phlorizin prevents glomerular hyperfiltration but not hypertrophy in diabetic rats. Exp Diabetes Res 2008, 2008: 305403. Epub 2008/09/05 10.1155/2008/305403View ArticlePubMedPubMed CentralGoogle Scholar
- Ren XJ, Guan GJ, Liu G, Zhang T, Liu GH: Effect of activin A on tubulointerstitial fibrosis in diabetic nephropathy. Nephrology (Carlton) 2009, 14(3):311–320. Epub 2009/03/21 10.1111/j.1440-1797.2008.01059.xView ArticleGoogle Scholar
- Arozal W, Watanabe K, Veeraveedu PT, Ma M, Thandavarayan RA, Suzuki K, Tachikawa H, Kodama M, Aizawa Y: Effects of angiotensin receptor blocker on oxidative stress and cardio-renal function in streptozotocin-induced diabetic rats. Biol Pharm Bull 2009, 32(8):1411–1416. Epub 2009/08/05 10.1248/bpb.32.1411View ArticlePubMedGoogle Scholar
- Sharma K, Ziyadeh FN: Hyperglycemia and diabetic kidney disease. The case for transforming growth factor-beta as a key mediator. Diabetes 1995, 44(10):1139–1146. Epub 1995/10/01 10.2337/diab.44.10.1139View ArticlePubMedGoogle Scholar
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