The Alteration of Plasma Matrix Metalloproteinase-9 Level after the Addition of Bromelin 500 mg to Standard Therapy of Acute Ischemic Stroke and Its Correlation with Outcome

Authors

  • Puji Pinta Sinurat Department of Neurology, Faculty of Medicine, Universitas Sumatera Utara, Medan
  • Hasan Sjahrir Department of Neurology, Faculty of Medicine, Universitas Sumatera Utara, Medan
  • Aldy S. Rambe Department of Neurology, Faculty of Medicine, Universitas Sumatera Utara, Medan
  • Ratna Akbari Ganie Department of Clinical Pathology, Faculty of Medicine, Universitas Sumatera Utara, Medan

DOI:

https://doi.org/10.3889/oamjms.2018.151

Keywords:

Acute Ischemic Stroke, Matrix Metalloproteinase-9, Bromelin, Outcome

Abstract

BACKGROUND: Matrix metalloproteinase-9 (MMP9) expression due to ischemic cause spreading of brain damage. Previous studies have reported that Bromelin was beneficial as anti-inflammation and prevent brain tissue damage.

AIM: This study aimed to determine the alteration of plasma MMP9 level after addition of Bromelin 500 mg to Standard therapy and its correlation with outcome in acute ischemic stroke.

METHODS: This was a preliminary report of a prospective randomised, double-blind study with pre and post-test design, forty-six acute ischemic stroke patients were randomly allocated with Bromelin and Standard groups. Measurement of MMP9 and outcome were performed before and after 14-days treatment.

RESULT: The Bromelin group showed a significant decrement of MMP9 level, from 6.02 ± 0.32 ng/ml before treatment to 5.50 ± 0.94 ng/ml after treatment (p = 0.028). There was a negative correlation between MMP9 level and mRS (r= -0.03; p = 0.905) and a positive correlation toward BI (r = 0.039; p = 0.859), while the Standard group showed increased MMP9 level from 5.82 ± 0.71 ng/ml to 5.91 ± 0.83 ng/ml (p = 0.616) which was correlated insignificantly to outcome.

CONCLUSION: We concluded that the addition of 500 mg Bromelin to standard ischemic stroke therapy reduced MMP9 level significantly and correlated to outcome improvement. However, there is a tight statistical correlation.

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Author Biographies

Puji Pinta Sinurat, Department of Neurology, Faculty of Medicine, Universitas Sumatera Utara, Medan

Faculty of Medicine, Neurology Department

Hasan Sjahrir, Department of Neurology, Faculty of Medicine, Universitas Sumatera Utara, Medan

Faculty of Medicine, Neurology Department

Aldy S. Rambe, Department of Neurology, Faculty of Medicine, Universitas Sumatera Utara, Medan

Faculty of Medicine, Neurology Department

Ratna Akbari Ganie, Department of Clinical Pathology, Faculty of Medicine, Universitas Sumatera Utara, Medan

Faculty of Medicine, Clinical Pathology Department

References

Brouns R, De Deyn PP. The complexity of neurobiological processes in acute ischemic stroke. Clinical Neurology and Neurosurgery. 2009; 111:483-95. https://doi.org/10.1016/j.clineuro.2009.04.001 PMid:19446389

Deb P, Sharma S, Hassan KM. Pathophysiologic mechanisms of acute ischemic stroke: An overview with emphasis on therapeutic significance beyond thrombolysis. Pathophysiology. 2010; 17(3):197-218. https://doi.org/10.1016/j.pathophys.2009.12.001 PMid:20074922

Jang JW, Lee JK, Hur H, Kim TW, Joo SP, Piao MS. Rutin improves functional outcome via reducing the elevated matrix metalloproteinase-9 level in a photothrombotic focal ischemic model of rats. Journal of the neurological sciences. 2014; 339(1):75-80. https://doi.org/10.1016/j.jns.2014.01.024 PMid:24507948

Yamashita T, Abe K. Therapeutic Approaches to Vascular Protection in Ischemic Stroke. Acta Medica Okayama. 2011; 4(65):219-23.

Morancho A, Roselli A, Garcia-Bonilla L,Montaner J. Metalloproteinase and Stroke Infarct Size: Role for Anti-inflammatory Treatment? Ann NY Acad Sci. 2010; 1207:123-33. https://doi.org/10.1111/j.1749-6632.2010.05734.x PMid:20955435

Nakase T, Yoshioka S, Suzuki A. Free radical scavenger, edaravone, reduces the lesion size of lacunar infarction in human brain ischemic stroke. BMC Neurology. 2011; 39:1-8. https://doi.org/10.1186/1471-2377-11-39

Lakhan SE, Kirchgessner A, Tepper D, Leonard A. Matrix Metalloproteinases and Blood-brain Barrier Disruption in Acute Ischemic Stroke. Stroke. 2013; 4:32. https://doi.org/10.3389/fneur.2013.00032

Reynolds MA, Kirchick HJ, Dahlen JR, Anderberg JM, McPherson PH, Nakamura KK, et al. Early Biomarkers of Stroke. Clinical Chemistry. 2003; 49:1733-9. https://doi.org/10.1373/49.10.1733 PMid:14500614

Worp HB, Gijn JV. Acute Ischemic Stroke. The New England Journal of Medicine. 2007; 357: 572-9. https://doi.org/10.1056/NEJMcp072057 PMid:17687132

Jordán J, Segura T, Brea D, Galindo MF, Castillo J. Inflammation as Therapeutic Objective in Stroke. Current Pharmaceutical Design. 2008; 14(33):3549-64. https://doi.org/10.2174/138161208786848766 PMid:19075732

Jin R, Yang G, Li G. Inflammatory Mechanisms in Ischemic Stroke: Role of Inflammatory Cells. J Leukoc Biol. 2010; 87(5):779-89. https://doi.org/10.1189/jlb.1109766 PMid:20130219 PMCid:PMC2858674

Saenger AK, Christenson RH. Stroke Biomarkers: Progress and Challenges for Diagnostic, Prognosis, Differentiation, and Treatment. Clinical Chemistry. 2010; 56(1):21-33. https://doi.org/10.1373/clinchem.2009.133801 PMid:19926776

Purba JS, Misbach J. Biomolekuler stroke', in Soertidewi L, Jannis J, editors. Stroke aspek diagnostik, patofisiologi, manajemen. Kelompok Studi Stroke Perhimpunan Dokter Spesialis Saraf Indonesia. Jakarta: Badan Penerbit FKUI, 2011: 41-52.

Cui J, Chen S, Zhang C, Meng F, Wu W, Hu R, et al. Inhibition of MMP-9 by a Selective Gelatinase Inhibitor Protects Neurovasculature from Embolic Focal Cerebral Ischemia. Mol Neurodegener. 2012; 15 (7):21. https://doi.org/10.1186/1750-1326-7-21 PMid:22587708 PMCid:PMC3500265

Xing C, Arai A, Lo EH, Hommer M. Pathophysiologic Cascades in Ischemic Stroke. Stroke. 2012; 7(5):378-85. https://doi.org/10.1111/j.1747-4949.2012.00839.x PMid:22712739 PMCid:PMC3985770

Chamorro A, Meisel A, Planas AM, Urra X, van de Beek D, Veltkamp R. The Immunology of Acute Stroke. Neurol. 2012; 8: 401-10. https://doi.org/10.1038/nrneurol.2012.98

Cojocaru IM, Cojocaru M, Sapira V, Socoliuc G, Hertea C, Paveliu S. Changes in Plasma Matrix Metalloproteinase-9 levels in Patients with Acute Ischemic Stroke. Rom J Intern Med. 2012; 50(2):155-8. PMid:23326959

Zlokovic BV. Remodeling after Stroke. a Promising Approach to Treating Ischemic Stroke, Inhibition of Matrix Metalloproteinases (MMPs), may Need to be Rethought. Nat Med. 2006; 12:390-1. https://doi.org/10.1038/nm0406-390 PMid:16598283

Yamashita T, Abe K. Therapeutic Approaches to Vascular Protection in Ischemic Stroke. Acta Medica Okayama. 2011; 4(65):219-23.

Pavan R, Jain S, Sharaddha, Kumar A. Properties and Therapeutic Application of Bromelain: a Review. Biotechnology Research International. 2012:1-6. https://doi.org/10.1155/2012/976203 PMid:23304525 PMCid:PMC3529416

Martins BC, Rescolino R, Coelcho DF, Zanchetta B, Tambourgi, EB, Silveira, E. Characterization of Bromelain from Ananas Comosus Agroindustrial Residues Purified by Ethanol Fractional Precipitation. Chemical Engineering Transactions. 2014; 37:781-6.

Bala M, Ismail, NA, Mel M, Jami MS, Salleh M, Amid A. Production: Current Trends and Perspective. Archives Des Sciences. 2012; 65(11).

Bhattacharyya BK. Bromelain: an Overview. Natural Product Radiance. 2007; 7(4):359-63.

Maurer HR. Bromelin: Biochemistry, Pharmacology and Medical Use. Cell Mol Life Sci. 2001; 58:1234-45. https://doi.org/10.1007/PL00000936 PMid:11577981

Tochi BN, Wang Z, Xu S-Y, Zhang W. Therapeutic Application of Pineaplle Protease (Bromelain): a Review.Pakistan Journal of Nutrition. 2008; 7(4):513-20. https://doi.org/10.3923/pjn.2008.513.520

Fileti AMF, Fischer GA, Tambourgi EB. Neural Modelling of Bromelain Extraction by Reversed Micelles. Brazilian Archives of Biology and Technology an International Journal. 2010; 53(2):455-63. https://doi.org/10.1590/S1516-89132010000200026

Ketnawa S, Sai-Ut S, Theppakorn T, Chaiwut P, Rawdkuen S. Partitioning of Bromelain from Pineapple Peel (nang lae cultv.) by Aquaeus Two Phase System. J Food Ag-Ind. 2012; 2:457-68.

Ferreira JF, Bresolin IRP, Silveira E, Tambourgi EB. Purification of Bromelain from Ananas Comosus by PEG/Phosphate ATPS, 2010.

Shiew PS, Fang YL, Abdul Majid FA. In Vitro Studyof Bromelain Activity in Artificial Stomach Juice and Blood Overview. Available from:www.cepp.utm.my/icbwi2010/pdf/

Wu SY, Hu W, Zhang B, Liu S, Wang JM, Wang AM. Bromelain Ameliorates the Wound Microenvironment and Improves the Healing of Firearm Wounds.Journal of Surgical Research. 2012; 176:503–9. https://doi.org/10.1016/j.jss.2011.11.1027 PMid:22341346

Candelario-Jalila E, Yanga Y, Rosenberg A. Diverse Roles Of Matrix Metalloproteinases and Tissue Inhibitors Of Metalloproteinases in Neuroinflammation and Cerebral Ischemia. Neuroscience. 2009; 158(3): 983–94. https://doi.org/10.1016/j.neuroscience.2008.06.025 PMid:18621108 PMCid:PMC3584171

Montaner J, Alvarez-Sabin J, Molina C, Angles A, Abilleira S, Arenillas J, et al. Matrix Metalloproteinase Expression After Human Cardioembolic Stroke: Temporal Profile and Relation to Neurological Impairment. Stroke. 2001; 32:1759-66. https://doi.org/10.1161/01.STR.32.8.1759 PMid:11486102

Abdelnaseera M, Elfayomia N, Hassana E, Kamalb M, Hamdyc A, Elsawya E. Serum Matrix Metalloproteinase-9 in Acute Ischemic Stroke and Its Relation to Stroke Severity. Egypt J Neurol Psychiat Neurosurg. 2015; 52:274–8. https://doi.org/10.4103/1110-1083.170661

Published

2018-04-06

How to Cite

1.
Sinurat PP, Sjahrir H, Rambe AS, Ganie RA. The Alteration of Plasma Matrix Metalloproteinase-9 Level after the Addition of Bromelin 500 mg to Standard Therapy of Acute Ischemic Stroke and Its Correlation with Outcome. Open Access Maced J Med Sci [Internet]. 2018 Apr. 6 [cited 2024 Mar. 28];6(4):624-8. Available from: https://oamjms.eu/index.php/mjms/article/view/oamjms.2018.151

Issue

Section

B - Clinical Sciences

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