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04-09-2023 | Cytokines | Original Article

The effect of magnesium sulfate on gene expression and serum level of inflammatory cytokines in coronary artery disease patients

Authors: Fatemeh Mohebi, Samane Ostadhadi, Mohammad sadegh Vaziri, Marziyeh Hassanzadeh, Shabnaz Koochakkhani, Fariba Azarkish, Hossein Farshidi, Ebrahim Eftekhar

Published in: Inflammopharmacology | Issue 5/2023

Abstract

Purpose

To evaluate the effect of oral magnesium sulfate (MgSO₄) on the gene expression and serum levels of inflammatory cytokines including TNF-α, IL-18, IL-1β, IL-6, and IFN-γ in patients with moderate coronary artery disease (CAD).

Methods

60 CAD patients were selected based on angiography findings and were randomly divided into two groups that received 300 mg/day MgSO₄ (n = 30) or placebo (n = 30) for 3 months. Gene expression and serum levels of inflammatory cytokines were assessed.

Results

After 3 months of intervention, gene expression and serum levels of IL-18 and TNF-α in the MgSO₄group were significantly less than the placebo group (P < 0.05). However, no significant difference in gene expression and serum levels of IL-1β, IL-6, and IFN-γ was observed between the two groups (P > 0.05). In addition, within group analysis demonstrate that Mg-treatment significantly decrease serum level of TNF-α and IL-18 as compared to pretreatment.

Conclusion

The results of our study demonstrate that 3-month magnesium sulfate administration (300 mg/day) to CAD patients could significantly decrease serum concentration and gene expression levels of IL-18 and TNF-α. Our findings support the potential beneficial effect of magnesium supplementation on alleviating CAD complications through modulating inflammatory cytokines.

Abbas AM, Sakr HF (2016) Effect of magnesium sulfate and thyroxine on inflammatory markers in a rat model of hypothyroidism. Can J Physiol Pharmacol 20(94):426–432CrossRef

Adrian M, Chanut E, Laurant P, Gaume V, Berthelot A (2008) A long-term moderate magnesium-deficient diet aggravates cardiovascular risks associated with aging and increases mortality in rats. J Hypertens 14(26):44–52. https://doi.org/10.1097/HJH.0b013e3282f09f68CrossRef

Brånén L, Hovgaard L, Nitulescu M, Bengtsson E, Nilsson J, Jovinge S (2004) Inhibition of tumor necrosis factor-alpha reduces atherosclerosis in apolipoprotein E knockout mice. Arterioscler Thromb Vasc Biol 7(24):2137–2142. https://doi.org/10.1161/01.ATV.0000143933.20616.1bCrossRef

Bruunsgaard H, Skinhøj P, Pedersen AN, Schroll M, Pedersen BK (2000) Ageing, tumour necrosis factor-alpha (TNF- α ) and atherosclerosis: ageing TNF-a and atherosclerosis. Clin Exp Immunol 19(121):255–260. https://doi.org/10.1046/j.1365-2249.2000.01281.xCrossRef

Chandrasekar B, Colston JT, de la Rosa SD, Rao PP, Freeman GL (2003) TNF-α and H2O2 induce IL-18 and IL-18Rβ expression in cardiomyocytes via NF-κB activation. Biochem Biophys Res Commun 21(303):1152–1158. https://doi.org/10.1016/S0006-291X(03)00496-0CrossRef

Chandrasekar B, Mummidi S, Valente AJ, Patel DN, Bailey SR, Freeman GL, Hatano M, Tokuhisa T, Jensen LE (2005) The pro-atherogenic cytokine interleukin-18 induces CXCL16 expression in rat aortic smooth muscle cells via MyD88, interleukin-1 receptor-associated kinase, tumor necrosis factor receptor-associated factor 6, c-Src, phosphatidylinositol 3-kinase, Akt, c-jun N-terminal kinase, and activator protein-1 signaling. J Biol Chem 27(280):26263–26277. https://doi.org/10.1074/jbc.M502586200CrossRef

Dinarello CA, Novick D, Kim S, Kaplanski G (2013) Interleukin-18 and IL-18 binding protein. Front Immunol 24:4. https://doi.org/10.3389/fimmu.2013.00289CrossRef

Farshidi H, Sobhani AR, Eslami M, Azarkish F, Eftekhar E, Keshavarz M, Soltani N (2020) Magnesium sulfate administration in moderate coronary artery disease patients improves atherosclerotic risk factors: a double-blind clinical trial study. J Cardiovasc Pharmacol 76:321–328. https://doi.org/10.1097/FJC.0000000000000874CrossRefPubMed

Gao F, Ding B, Zhou L, Gao X, Guo H, Xu H (2013) Magnesium sulfate provides neuroprotection in lipopolysaccharide-activated primary microglia by inhibiting NF-κB pathway. J Surg Res 37(184):944–950. https://doi.org/10.1016/j.jss.2013.03.034CrossRef

Gerdes N, Sukhova GK, Libby P, Reynolds RS, Young JL, Schönbeck U (2002) Expression of interleukin (IL)-18 and functional IL-18 receptor on human vascular endothelial cells, smooth muscle cells, and macrophages. J Exp Med 26(195):245–257. https://doi.org/10.1084/jem.20011022CrossRef

Gisterå A, Hansson GK (2017) The immunology of atherosclerosis. Nat Rev Nephrol 10(13):368–380. https://doi.org/10.1038/nrneph.2017.51CrossRef

Hansson GK, Hermansson A (2011) The immune system in atherosclerosis. Nat Immunol 1(12):204–212. https://doi.org/10.1038/ni.2001CrossRef

Hartman J, Frishman WH (2014) Inflammation and atherosclerosis: a review of the role of interleukin-6 in the development of atherosclerosis and the potential for targeted drug therapy. Cardiol Rev 29(22):147–151. https://doi.org/10.1097/CRD.0000000000000021CrossRef

Huber SA, Sakkinen P, Conze D, Hardin N, Tracy R (1999) Interleukin-6 exacerbates early atherosclerosis in mice. Arterioscler Thromb Vasc Biol 32(19):2364–2367. https://doi.org/10.1161/01.ATV.19.10.2364CrossRef

Joris PJ, Plat J, Bakker SJ, Mensink RP (2016) Long-term magnesium supplementation improves arterial stiffness in overweight and obese adults: results of a randomized, double-blind, placebo-controlled intervention trial. Am J Clin Nutr 103:1260–1266. https://doi.org/10.3945/ajcn.116.131466CrossRefPubMed

Kaptoge S, Seshasai SRK, Gao P, Freitag DF, Butterworth AS, Borglykke A, Di Angelantonio E, Gudnason V, Rumley A, Lowe GDO, Jorgensen T, Danesh J (2014) Inflammatory cytokines and risk of coronary heart disease: new prospective study and updated meta-analysis. Eur Heart J 30(35):578–589. https://doi.org/10.1093/eurheartj/eht367CrossRef

Karasawa T, Takahashi M (2017) Role of NLRP3 inflammasomes in atherosclerosis. J Atheroscler Thromb 3(24):443–451. https://doi.org/10.5551/jat.RV17001CrossRef

Kim DJ, Xun P, Liu K, Loria C, Yokota K, Jacobs DR, He K (2010) Magnesium intake in relation to systemic inflammation, insulin resistance, and the incidence of diabetes. Diabetes Care 33(33):2604–2610. https://doi.org/10.2337/dc10-0994CrossRefPubMedPubMedCentral

Lei X, Buja LM (1996) Detection and localization of tumor necrosis factor-α in WHHL rabbit arteries. Atherosclerosis 17(125):81–89CrossRef

Libby P, Ridker PM, Hansson GK (2009) Inflammation in atherosclerosis. J Am Coll Cardiol 16(54):2129–2138. https://doi.org/10.1016/j.jacc.2009.09.009CrossRef

Lin CY, Tsai PS, Hung YC, Huang CJ (2010) L-type calcium channels are involved in mediating the anti-inflammatory effects of magnesium sulphate. Br J Anaesth 38(104):44–51. https://doi.org/10.1093/bja/aep336CrossRef

Lusis AJ (2000) Atherosclerosis. Nature 2(407):233–241. https://doi.org/10.1038/35025203CrossRef

Mallat Z, Corbaz A, Scoazec A, Besnard S, Lesèche G, Chvatchko Y, Tedgui A (2001) Expression of interleukin-18 in human atherosclerotic plaques and relation to plaque instability. Circulation 25(104):1598–1603. https://doi.org/10.1161/hc3901.096721CrossRef

McLean AS, Huang SJ, Salter M (2008) Bench-to-bedside review: the value of cardiac biomarkers in the intensive care patient. Crit Care Lond Engl 6(12):215. https://doi.org/10.1186/cc6880CrossRef

Moriya J (2019) Critical roles of inflammation in atherosclerosis. J Cardiol 35(73):22–27. https://doi.org/10.1016/j.jjcc.2018.05.010CrossRef

Muga MA, Chao JC-J (2014) Effects of fish oil and spirulina on oxidative stress and inflammation in hypercholesterolemic hamsters. BMC Complement Altern Med 9(14):470. https://doi.org/10.1186/1472-6882-14-470CrossRef

Naghipour B, Faridaalaee G, Shadvar K, Bilehjani E, Khabaz A, Fakhari S (2016) Effect of prophylaxis of magnesium sulfate for reduction of postcardiac surgery arrhythmia: randomized clinical trial. Ann Card Anaesth 13(19):662. https://doi.org/10.4103/0971-9784.191577CrossRef

Ridker PM (2016) From C-reactive protein to interleukin-6 to interleukin-1: moving upstream to identify novel targets for atheroprotection. Circ Res 31(118):145–156. https://doi.org/10.1161/CIRCRESAHA.115.306656CrossRef

Ridker PM, Rifai N, Stampfer MJ, Hennekens CH (2000) Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation 8(101):1767–1772. https://doi.org/10.1161/01.CIR.101.15.1767CrossRef

Schutten JC, Joris PJ, Groendijk I, Eelderink C, Groothof D, van der Veen Y, Westerhuis R, Goorman F, Danel RM, de Borst MH, Bakker SJL (2022) Effects of magnesium citrate, magnesium oxide, and magnesium sulfate supplementation on arterial stiffness: a randomized, double-blind, placebo-controlled intervention trial. J. Am. Heart Assoc. 11:e021783. https://doi.org/10.1161/JAHA.121.021783CrossRefPubMedPubMedCentral

Shi C-X, Qi Q-H, Xu J, Zhao WW (2020) Protective effect of magnesium sulfate on cranial nerves in preeclampsia rats through NF-κB/ICAM-1 pathway. Eur. Rev. Med. Pharmacol. Sci. 24:2785–2794. https://doi.org/10.26355/eurrev_202003_20639CrossRefPubMed

Song Y, Li TY, van Dam RM, Manson JE, Hu FB (2007) Magnesium intake and plasma concentrations of markers of systemic inflammation and endothelial dysfunction in women. Am J Clin Nutr 34(85):1068–1074. https://doi.org/10.1093/ajcn/85.4.1068CrossRef

Sugimoto J et al (2012) Magnesium decreases inflammatory cytokine production: a novel innate immunomodulatory mechanism. J. Immunol. 36(188):6338–6346. https://doi.org/10.4049/jimmunol.1101765CrossRef

Tangvoraphonkchai K, Davenport A (2018) Magnesium and cardiovascular disease. Magnesium 15(25):251–260. https://doi.org/10.1053/j.ackd.2018.02.010CrossRef

Tedgui A, Mallat Z (2006) Cytokines in atherosclerosis: pathogenic and regulatory pathways. Physiol Rev 5(86):515–581. https://doi.org/10.1152/physrev.00024.2005CrossRef

Tousoulis D, Oikonomou E, Economou EK, Crea F, Kaski JC (2016) Inflammatory cytokines in atherosclerosis: current therapeutic approaches. Eur Heart J 11(37):1723–1732. https://doi.org/10.1093/eurheartj/ehv759CrossRef

Wood IS, Wang B, Jenkins JR, Trayhurn P (2005) The pro-inflammatory cytokine IL-18 is expressed in human adipose tissue and strongly upregulated by TNFα in human adipocytes. Biochem Biophys Res Commun 23(337):422–429. https://doi.org/10.1016/j.bbrc.2005.09.068CrossRef

Yang X, Jia J, Yu Z, Duanmu Z, He H, Chen S, Qu C (2020) Inhibition of JAK2/STAT3/SOCS3 signaling attenuates atherosclerosis in rabbit. BMC Cardiovasc Disord 18(20):133. https://doi.org/10.1186/s12872-020-01391-7CrossRef

Yu X, Guan P-P, Zhu D, Liang Y-Y, Wang T, Wang Z-Y, Wang P (2018) Magnesium ions inhibit the expression of tumor necrosis factor α and the activity of γ-secretase in a β-amyloid protein-dependent mechanism in APP/PS1 transgenic mice. Front Mol Neurosci 21(11):172. https://doi.org/10.3389/fnmol.2018.00172CrossRef

Zhang LW, Warrington JP (2016) Magnesium sulfate prevents placental ischemia-induced increases in brain water content and cerebrospinal fluid cytokines in pregnant rats. Front Neurosci 28:10. https://doi.org/10.3389/fnins.2016.00561CrossRef

Zhu D, You J, Zhao N, Xu H (2019) Magnesium regulates endothelial barrier functions through TRPM7, MagT1, and S1P1. Adv Sci 12(6):1901166. https://doi.org/10.1002/advs.201901166CrossRef

Title: The effect of magnesium sulfate on gene expression and serum level of inflammatory cytokines in coronary artery disease patients
Authors: Fatemeh Mohebi
Samane Ostadhadi
Mohammad sadegh Vaziri
Marziyeh Hassanzadeh
Shabnaz Koochakkhani
Fariba Azarkish
Hossein Farshidi
Ebrahim Eftekhar
Publication date: 04-09-2023
Publisher: Springer International Publishing
Keywords: Cytokines
Arterial Diseases
Published in: Inflammopharmacology / Issue 5/2023
Print ISSN: 0925-4692
Electronic ISSN: 1568-5608
DOI: https://doi.org/10.1007/s10787-023-01328-4

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Springer Medicine

The effect of magnesium sulfate on gene expression and serum level of inflammatory cytokines in coronary artery disease patients

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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