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
DOI:
https://doi.org/10.3889/oamjms.2018.151Keywords:
Acute Ischemic Stroke, Matrix Metalloproteinase-9, Bromelin, OutcomeAbstract
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.Downloads
Metrics
Plum Analytics Artifact Widget Block
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
Downloads
Published
How to Cite
Issue
Section
License
http://creativecommons.org/licenses/by-nc/4.0