Nanotechnology in Metformin Delivery: Fasting Blood Glucose and Neutrophil-Lymphocyte Ratio of Diabetic Rat Model

David Pakaya, Laurents Christovel Iban Demen, Haerani Harun, Sarifuddin Anwar, Gabriella Bamba Ratih Lintin

Abstract


Diabetes Mellitus (DM) is a chronic inflammatory disease characterized by hyperglycemia and increasing the neutrophil-lymphocyte ratio (NLR). Metformin has been widely used to treat hyperglycemia. Metformin nanoparticles can improve bioavailability and may reduce inflammation. This study aims to analyze the effectiveness of metformin nanoparticles delivery through fasting blood glucose (FGB) level and NLR in the diabetic rat model. This study used 16 white male Wistar rats, 8 weeks of age, and body weight (BW) 250-350 grams. The streptozotocin (STZ) 40 mg/kg BW were injected i.p. Rats were divided into 4 groups; K1: normal control; K2: negative control (diabetes model); K3: diabetes model treated with metformin 100mg/Kg BW; K4: diabetes model treated with nanoparticle metformin 100mg/kg BW. Blood analysis tests were conducted using the Pentra hematology analyzer. Data were analyzed using the Graphpad Prism program with the nonparametric Kruskal Wallis test. The K3 group showed a periodical decrease in FBG level from day 7 to day 28 by 122 ± 11.31 mg/dL, and the mean NLR value was 0.48 ± 0.3 x 103/uL. Group of K4 periodically decreased in FBG level, indicating that it was closer to normal than K3. The result showed that at day 28.79 ± 15.39 mg/dL, the mean NLR value slightly increased compared to the K3 group by 0.54 ± 0.3 x103/uL. The statistical tests showed a significant difference between the level of FBG (p 0.0089) but no significant difference in NLR (p 0.347). Metformin nanoparticles could decrease FBG levels and effectively reduce the NLR in the diabetic rat model.

Keywords


Diabetes Mellitus; Metformin; Nanoparticles; Neutrophil-lymphocyte Ratio

Full Text:

PDF

References


International Diabetes Federation. 2013. IDF Diabetes Atlas sixth edition. IDF: Brussels.

World Health Organization. (2014). Diabetes Mellitus. WHO News: Fact Sheet. WHO: Geneva.

Wibisana KA, Subekti I, Antono D, dan Nugroho P. Hubungan antara Rasio Neutrofil Limfosit dengan Kejadian Penyakit Arteri Perifer Ekstremitas Bawah pada Penyandang Diabetes Melitus Tipe 2. Jurnal Penyakit Dalam Indonesia. 2018:5(4)184-188. http://dx.doi.org/10.7454/jpdi.v5i4.227

Hongdiyanto A, dan Yamlean PVY. Evaluasi Kerasionalan Pengobatan Diabetes Melitus Tipe 2 pada Pasien Rawat Inap di RSUP Prof. Dr. R. D. Kandou Manado Tahun 2013. Pharmacon. 2014:3(2):77-86. https://doi.org/10.35799/pha.3.2014.4775

Janić M, Volčanšek Š, Lunder M, and Janež A. 2017. Metformin: from mechanisms of action to advanced clinical use. Zdrav Vestn. 2017:86:138-1457. https://doi.org/10.6016/ZdravVestn.1503

Alhalmi A, Alzubaidi N, and Abdulmalik W. Current Advances in Nanotechnology for Delivery of Anti-Diabetic Drugs: A Review. Int J Pharmacog. 2018:5(1):1-7. https://doi.org/10.13040/IJPSR.0975-8232.IJP.5(1).1-07

Pereira A, Brito G, Lima M, Silva Júnior A, Silva E, de Rezende A, et al. Metformin Hydrochloride-Loaded PLGA Nanoparticle in Periodontal Disease Experimental Model Using Diabetic Rats. Int J Mol Sci. 2018:19(11)3488. https://doi.org/10.3390/ijms19113488

Hasanah A. Efek Jus Bawang Bombay (Alium cepa Linn.) terhadap Mortalitas Spermatozoa Mencit yang Diinduksi Streptozotocin (STZ). Saintika Medika: Jurnal Ilmu Kesehatan dan Kedokteran Keluarga. 2015;11(2):92-101. https://doi.org/10.22219/sm.v11i2.4203

Putra RJS, Achmad A, dan Rachma H. Kejadian Efek Samping Potensial Terapi Obat Anti Diabetes Pasien Diabetes Melitus Berdasarkan Algoritma Naranjo. Pharmeceutical Journal of Indonesia. 2017:2(2):45-50.

Zufry H. Terapi Farmakologis pada Obesitas. Jurnal Kedokteran Syiah Kuala. 2010:10(3):157-168.

Saputra TN, Suartha N, dan Dharmayudha OGAA. Agen Diabetogenik Streptozotocin untuk Membuat Tikus Putih Jantan Diabetes Melitus. Buletin Veteriner Udayana. 2018;10(2):116-121. https://doi.org/10.24843/bulvet.2018.v10.i02.p02

Katzung B.G. Farmakologi Dasar dan Klinik. EGC: Jakarta. 2016.

Fitria L, dan Sarto M. Profil Hematologi Tikus (Rattus norvegicus Berkenhout, 1769) Galur Wistar Jantan dan Betina Umur 4, 6, dan 8 Minggu. Biogenesis. 2014:2, 2(2):94–100. https://doi.org/10.24843/bulvet.2018.v10.i02.p02

Cameron AR , Morrison VL, Levin D, Mohan M, Forteath C, Beall C, et al. Antiinflamatory Effect of Metformin Irrespective of Diabetes Status. Circ Res. 2016. 1(19):652-665. https://doi.org/10.1161/CIRCRESAHA.116.308445

Wang X, Zhang G, Jiang X, Zhu H, Lu Z, and Xu L. Neutrophil to Lymphocyte Ratio in Relation to Risk of All-Cause Mortality and Cardiovascular Events among Patients undergoing Angiopraphy or Cardiac Revascularization: A Meta-Analysis of Observational Studies. Atherosclerosis. 2014: 234:206-213. https://doi.org/10.1016/j.atherosclerosis.2014.03.003

Ip B, Clifone N, Zhu M, Kuchibhatla RA, Zer M, McDonnell M, et al. An Inflammatory T Cell Signature Predicts Obesity Associated Type 2 Diabetes. J. Immunol, 2015; 1-94: 121-122.

Wong AKF, Symon R, Alzadjali MA, Ang DSC, Ogston S, Choy AM, et al. The effect of metformin on insulin resistance and exercise parameters in patients with heart failure. Eruopean Journal of Heart Failure. 2012:14:1303-1310. https://doi.org/10.1093/eurjhf/hfs106

Vasamsetti SB, Karnevewar S, Kanugula AK, Thatipali AR, Kumar JM, Kotamraju S. Metformin Inhibits Monocyte to Macrophage Differentiation Via AMPK Mediated Inhibition of STAT3 Activation: Potential Role in Atherosclerosis. Diabetes. 2015; 64:2028-2041. https://doi.org/10.2337/db14-1225

Rena G, Hardie G, and Pearson ER. The Mechanism of Action of Metformin. Diabetologia. 2017; 601:1577-1585. https://doi.org/10.1007/s00125-017-4342-z

Griffin SJ, Leaver JK, Irving GJ. Impact of Metformin on Cardiovascular Disease: A Meta-analysis of Randomised Trials among People with Type 2 Diabetes. Diabetologia. 2017; 60(9):1620-1629. https://doi.org/10.1007/s00125-017-4337-9




DOI: https://doi.org/10.18196/mmjkk.v22i1.13358

Refbacks

  • There are currently no refbacks.


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

      

Editorial Office:
Journal Room, G1 (Biomedic) Building, Ground Floor, Faculty of Medicine and Health Science Universitas Muhammadiyah Yogyakarta, 
Jalan Lingkar Selatan (Brawijaya), Tamantirto, Kasihan, Bantul, Daerah Istimewa Yogyakarta, Indonesia
Phone: +62 274 387 656 (ext: 231)
WA : +62 811-2650-303
Website: http://journal.umy.ac.id/index.php/mm 
E-mail: mmjkk@umy.university

Creative Commons License
Mutiara Medika: Jurnal Kedokteran dan Kesehatan is licensed under a Creative Commons Attribution 4.0 International License. View My Stats