Modeling Hyperglycemia With Induction Variants In Mice As Preclinical Test Animals
Abstract
Inducing hyperglycemia in animal models is crucial for preclinical research on anti-diabetic drug development, especially when genetically diabetic test animals are unavailable. Various induction methods have been employed to elevate glycemic levels in test animals. However, there is a lack of substantial literature proving the effectiveness and stability of these induction alternatives. This study aims to compare the stability of glycemic levels and assess histopathological changes in mice induced by dextrose, streptozotocin, and alloxan. Our protocol involved dividing mice into six groups of five, each with a control group. Mice in Groups A and D were exposed to alloxan monohydrate, Groups B and E to streptozotocin, and Groups C and F to dextrose monohydrate, inducing hyperglycemia for nine days following a seven-day acclimatization period. Pancreatic histopathology examination included features such as cytoplasmic vacuolization, fat infiltration, and islet deformation. The study revealed that, compared to dextrose and streptozocin, alloxan demonstrated superior efficacy in inducing and maintaining hyperglycemic stability in mice. However, the histopathological assessment of the pancreas indicated the relatively benign nature of dextrose monohydrate and streptozotocin, with no apparent exacerbation of pancreatic impairment. In contrast, alloxan induced evident islet deformation and cytoplasmic vacuolization. Our findings suggest that, in comparison to alloxan, dextrose monohydrate and streptozotocin are more favorable for inducing hyperglycemia in test animals. They pose a lower risk of significant pancreatic impairment, indicating their potential suitability for modeling type 2 diabetes mellitus due to their stability and relatively benign impact on pancreatic histopathology.
Keywords
Full Text:
PDFReferences
Dyah A. Perwitasari, Setiyo B. Santosa, Imaniar N. Faridah, and Adrian A. Kaptein, ‘Illness Perceptions and Quality of Life in Patients with Diabetes Mellitus Type 2’, Indones J Clin Pharm, vol. 6, no. 3, pp. 190–199, Sep. 2017, doi: 10.15416/ijcp.2017.6.3.190.
S. B. Santoso, D. A. Perwitasari, I. N. Faridah, and A. A. Kaptein, ‘Hubungan kualitas hidup dan persepsi pasien tentang penyakit diabetes mellitus tipe 2 dengan komplikasi’, Pharmaciana, vol. 7, no. 1, p. 33, May 2017, doi: 10.12928/pharmaciana.v7i1.4699.
H. W. Baynest, ‘Classification, Pathophysiology, Diagnosis and Management of Diabetes Mellitus’, J Diabetes Metab, vol. 06, no. 05, 2015, doi: 10.4172/2155-6156.1000541.
A. King and A. Austin, ‘Chapter 10 - Animal Models of Type 1 and Type 2 Diabetes Mellitus’, Diabetes Mellitus, p. 21, 2017.
R. N. Fatimah, ‘Diabetes Melitus Tipe 2’, Jurnal Majority, vol. 4, pp. 93–101, 2015.
N. Apriani, E. Suhartono, and I. Z. Akbar, ‘Korelasi Kadar Glukosa Darah dengan Kadar Advanced Oxidation Protein Products (AOPP) Tulang pada Tikus Putih Model Hiperglikemia’, Jurnal Kesehatan Masyarakat, vol. 11, pp. 48–55, Jul. 2011.
A. Hasanah, ‘Efek Jus Bawang Bombay (allium Cepa Linn.) Terhadap Motilitas Spermatozoa Mencit yang diinduksi Streptozotocin (STZ)’, SM, vol. 11, no. 2, p. 92, Mar. 2017, doi: 10.22219/sm.v11i2.4203.
I. A. K. Pramushinta, U. Nurhayati, and Sukarjati, ‘Potensi Ekstrak Etanol Daun Sambung Nyawa (Gynura procumbens), Biji Mahoni (Swietenia mahagoni jacq )serta Kombinasi Kedua Ekstrak sebagai Herbal Anti Diabetik Dengan Hewan Coba Mencit (Mus musculus L.)’, Seminar Nasional Hasil Riset dan Pengabdian, pp. 443–449, 2019.
S. D. Santoso and I. Suryanto, ‘Komparasi Efek Pemberian Minyak Jintan Hitam (nigella Sativa) dengan Minyak Zaitun (olea Europea) terhadap Penurunan Glukosa Darah pada Mencit (mus Musculus) Strain Balb/C’, JSH, vol. 1, no. 1, p. 36, May 2017, doi: 10.51804/jsh.v1i1.76.36-42.
R. A. Nugroho, Mengenal Mencit sebagai Hewan Uji Laboratorium. Samarinda: Mulawarman University Press, 2018.
D. Y. S. Putra, S. B. Santoso, and H. Lutfiyati, ‘The Weight Performance Stability of Mice on Modeling Obesity-Associated Hyperglycemia Induced by Dextrose Monohydrate’, BIOMEDNATPROCH, vol. 11, no. 2, pp. 169–173, Sep. 2022, doi: 10.14421/biomedich.2022.112.169-173.
S. B. Santoso, W. S. Hapsari, and R. Setyowati, ‘Modeling of Mice as Test Animals for a Preclinical Study of Hypolipidemic Agents’, JFSP, vol. 9, no. 2, pp. 185–192, Aug. 2023, doi: 10.31603/pharmacy.v9i2.8463.
S. J. Glastras et al., ‘Mouse Models of Diabetes, Obesity and Related Kidney Disease’, PLoS ONE, vol. 11, no. 8, p. e0162131, Aug. 2016, doi: 10.1371/journal.pone.0162131.
F. M. S. Putri, ‘Urgensi Etika Medis dalam Penanganan Mencit pada Penelitian Farmakologi’, urnal Kesehatan Madani Medika, vol. 9, no. 2, p. 11, 2018.
C. P. D. Kottaisamy, D. S. Raj, V. Prasanth Kumar, and U. Sankaran, ‘Experimental animal models for diabetes and its related complications—a review’, Lab Anim Res, vol. 37, no. 1, p. 23, Dec. 2021, doi: 10.1186/s42826-021-00101-4.
A. Al-awar et al., ‘Experimental Diabetes Mellitus in Different Animal Models’, Journal of Diabetes Research, vol. 2016, pp. 1–12, 2016, doi: 10.1155/2016/9051426.
Irdalisa, Safrida, Khairil, Abdullah, and M. Sabri, ‘Profil Kadar Glukosa Darah pada Tikus Setelah Penyuntikan Aloksan sebagai Hewan Model Hiperglikemik’, Jurnal EduBio Tropika, vol. Vol 3, pp. 1–50, Apr. 2015.
R. S. Dewi, L. Rahayu, and I. Atika, ‘Efek Penurunan Kadar Glukosa Darah Rebusan Asparagus (Asparagus officinalis L.) pada Mencit yang diinduksi Aloksan’, Jurnal Ilmu Kefarmasian Indonesia, vol. 19, pp. 56–61, 2021.
N. Lolok, H. Rahmat, and P. M. Wijayanti, ‘Efek Antidiabetes Kombinasi Ekstrak Kulit Bawang Dayak Dan Kulit Bawang Merah Pada Mencit Yang Diinduksi Aloksan’, Jurnal Mandala Pharmacon Indonesia, vol. 5, 2019.
R. Ocktarini, D. H. Prasetyo, and I. Sjarifah, ‘Effect of Herbal Extract of Anting-Anting (acalypha Australis) on Blood Glucose Level of Balb/C Mice with Induction of Streptozotocin’, J Nat Prod Biochem, vol. 9, no. 1, pp. 12–16, Feb. 2011, doi: 10.13057/biofar/f090103.
Suwanto and R. Rahmawati, ‘Aktivitas Hipoglikemik Diet Pakan Ekstrak Biji Labu Kuning (Cucurbita moschata Duch) pada Mencit Diabetes Melitus Terpapar Streptozotocin’, Journal of Pharmaceutical Science and Clinical Research, pp. 39–41, 2019, doi: DOI: 10.20961/jpscr.v4i1.27292.
Akrom, P. D. Harjanti, and T. Armansyah, ‘Efek Hipoglikemik Ekstrak Etanol Umbi Ketela Rambat (ipomoea Batatas P) ( Eeuk R) pada Mencit Swiss yang Diinduksi Aloksan’, Pharmaçiana, vol. 4, pp. 65–76, 2014.
A. Rohilla and S. Ali, ‘Alloxan Induced Diabetes: Mechanisms and Effects’, vol. 3, p. 5, 2012.
T. Szkudelski, ‘The Mechanism of Alloxan and Streptozotocin Action in B Cells of the Rat Pancreas’, Physiol Res, 2001.
B. L. Furman, ‘Streptozotocin‐Induced Diabetic Models in Mice and Rats’, Current Protocols in Pharmacology, vol. 70, no. 1, Sep. 2015, doi: 10.1002/0471141755.ph0547s70.
M. Abdollahi and A. Hosseini, ‘Streptozotocin’, in Encyclopedia of Toxicology, Elsevier, 2014, pp. 402–404. doi: 10.1016/B978-0-12-386454-3.01170-2.
C. D. F. Ira and C. I. NHS, ‘Sebagai Antihiperglikemia pada Mencit (Mus musculus) yang Diinduksi Dextrosa Monohidrat 40%’, Journal of Pharmaceutical Science and Pharmacy Practice, vol. Volume 2, pp. 27–32, 2015.
F. Pasaribu, P. Sitorus, and S. Bahri, ‘The Testof Ethanol Extract of Mangosteen Rind (Garcinia mangostana L) to Decrease Blood Glucose Level’, Journal of Pharmaceutics and Pharmacology, vol. 1, 2012.
J. T. DiPiro, G. C. Yee, L. M. Posey, S. T. Haines, T. D. Nolin, and V. Ellingrod, Eds., Pharmacotherapy: A Pathophysiologic Approach, Eleventh edition. New York: McGraw Hill Medical, 2020.
O. M. Prameswari and S. B. Widjanarko, ‘Uji Efek Ekstrak Air Daun Pandan Wangi terhadap Penurunan Kadar Glukosa Darah dan Histopatologi Tikus Diabetes Mellitus’, Jurnal Pangan dan Agroindustri, p. 12, 2014.
S. A. Soelistijo, et al., Pengelolaan dan Pencegahan Diabetes Melitus Tipe 2 di Indonesia 2015. Indonesia: PB. PERKENI, 2015.
I. Pernicova and M. Korbonits, ‘Metformin: Mode of Action and Clinical Implications for Diabetes and Cancer’, Advance Online Publication, vol. Volume 10, 2014.
D. S. Longnecker, ‘Anatomy and Histology of the Pancreas’. 2021. doi: 10.3998/panc.2021.01.
R. Shah, F. Subhan, S. M. Sultan, G. Ali, I. Ullah, and S. Ullah, ‘Comparative evaluation of pancreatic histopathology of rats treated with olanzapine, risperidone and streptozocin’, Braz. J. Pharm. Sci., vol. 54, no. 3, Nov. 2018, doi: 10.1590/s2175-97902018000317669.
M. Walvekar, S. Deasi, and N. D. Potphode, ‘Histological Studies on Islets of Langerhans of Pancreas in Diabetic Mice After Curcumin Administration’, International Journal of Pharmaceutical and Clinical Research, vol. 8, no. 9, 2016.
M. Abdul-Hamid and N. Moustafa, ‘Protective effect of curcumin on histopathology and ultrastructure of pancreas in the alloxan treated rats for induction of diabetes’, The Journal of Basic & Applied Zoology, vol. 66, no. 4, pp. 169–179, Aug. 2013, doi: 10.1016/j.jobaz.2013.07.003.
S. Hutahaean, S. Ilyas, and S. Rahayu, ‘Histological Change of Pancreatic Islands Following Administration of Saurauia vulcani Korth Leaves Extract in Alloxan-induced Diabetic Mice’:, in Proceedings of the International Conference of Science, Technology, Engineering, Environmental and Ramification Researches, Medan, Indonesia: SCITEPRESS - Science and Technology Publications, 2018, pp. 1095–1098. doi: 10.5220/0010104010951098.
C. Zhang et al., ‘Antihyperglycaemic and organic protective effects on pancreas, liver and kidney by polysaccharides from Hericium erinaceus SG-02 in streptozotocin-induced diabetic mice’, Sci Rep, vol. 7, no. 1, p. 10847, Dec. 2017, doi: 10.1038/s41598-017-11457-w.
K. N. Gibson-Corley, D. K. Meyerholz, and J. F. Engelhardt, ‘Pancreatic pathophysiology in cystic fibrosis’, Wiley Online Library, 2015.
P. Ningsih et al., ‘Histology of hematoxylin–eosin and immunohistochemical diabetes rat pancreas after giving combination of moringa leaves (Moringa oleifera) and clove flower (Syzygium aromaticum) extracts’, Open Access Maced J Med Sci, vol. 9, no. A, pp. 257–262, May 2021, doi: 10.3889/oamjms.2021.5928.
DOI: https://doi.org/10.15416/pcpr.v9i1.52119
Refbacks
- There are currently no refbacks.
