A Rat Experimental Model for Investigation of the Effect of Diabetes on Submandibular Salivary Glands Treated with Epidermal Growth Factor

Authors

DOI:

https://doi.org/10.3889/oamjms.2022.9209

Keywords:

Submandibular salivary gland, Epidermal growth factor, Diabetes, Streptozotocin, Myosin

Abstract

Background: Despite the plethora of research around the negative effects of diabetes on different body organs, this topic still attracts a lot of attention in order to find potential remedies that could counteract or reverse the damaging effect of diabetes.

Aim: In this study, we developed a reliable experimental rat model that can be used for investigation of the ability of epidermal growth factor (EFG) in restoring the normal architecture of oral tissues after being damaged by diabetes.

Methods: Eighty adult male albino rats (average weight ±220 gm) were used in the current study. Twenty rats served as control and received no treatment. Diabetes was induced in forty rats using a single injection of 65mg/kg of Streptozotocin (STZ). Out of the forty diabetic rats, twenty rats received a single daily intraperitoneal injection of EGF (10 µg/Kg) for 8 weeks. Furthermore, twenty healthy rats received the same dose of EGF and served as positive controls. The submandibular salivary glands of all rats were examined for Immunohistochemical detection of myosin in the glandular structure.

Results: The EGF treated group showed comparable myosin expression to the control group. The diabetic group revealed deterioration of all components of the submandibular salivary glands. Finally, the diabetic + EGF group has demonstrated restoration of the myosin expression levels in the submandibular salivary glands to a level that is not significantly different from healthy (non-diabetic) rats in the control group (p>0.05) and significantly higher than the diabetic group (p<0.0001).

Conclusion: The findings of the present study confirm previous studies and validates the use of our animal model as predictable experimental tool to investigate the effects of diabetes and EGF on different oral tissues. It also highlights the importance of further research investigating EGF as a promising treatment modality for restoration of the condition and functions of tissues damaged by diabetes not only in the oral cavity but also around the whole body.  

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

References

Rees DA, Alcolado JC. Animal models of diabetes mellitus. Diabet Med. 2005;22(4):359-70. https://doi.org/10.1111/j.1464-5491.2005.01499.x PMid:15787657 DOI: https://doi.org/10.1111/j.1464-5491.2005.01499.x

McMurray G, Casey JH, Naylor AM. Animal models in urological disease and sexual dysfunction. Br J Pharmacol. 2006;147 (Suppl 2):S62-79. https://doi.org/10.1038/sj.bjp.0706630 PMid:16465185 DOI: https://doi.org/10.1038/sj.bjp.0706630

Chatzigeorgiou A, Halapas A, Kalafatakis K, Kamper E. The use of animal models in the study of diabetes mellitus. In Vivo. 2009;23(2):245-58. PMid:19414410

Vickers SP, Jackson HC, Cheetham SC. The utility of animal models to evaluate novel anti-obesity agents. Br J Pharmacol. 2011;164(4):1248-62. https://doi.org/10.1111/j.1476-5381.2011.01245.x PMid:21265828 DOI: https://doi.org/10.1111/j.1476-5381.2011.01245.x

Chen D, Wang MW. Development and application of rodent models for type 2 diabetes. Diabetes Obes Metab. 2005;7(4):307-17. https://doi.org/10.1111/j.1463-1326.2004.00392.x PMid:15955116 DOI: https://doi.org/10.1111/j.1463-1326.2004.00392.x

Islam MS, Loots du T. Experimental rodent models of type 2 diabetes: A review. Methods Find Exp Clin Pharmacol. 2009;31(4):249-61. https://doi.org/10.1358/mf.2009.31.4.1362513 PMid:19557203 DOI: https://doi.org/10.1358/mf.2009.31.4.1362513

King JFA. The use of animal models in diabetes research. Br J Pharmacol. 2012;166(3):877-94. https://doi.org/10.1111/j.1476-5381.2012.01911.x PMid:22352879 DOI: https://doi.org/10.1111/j.1476-5381.2012.01911.x

World Health Organization. About Diabetes. Geneva: World Health Organization; 2022.

Ebuehi OA, Ajuluchukwu AE, Afolabi OT, Akinwande AI. Oxidative stress in alloxan-induced diabetes in female and male rats. Adv Med Dent Sci. 2010;3(3):71-5.

Williams JC, Pickup G. Complications of diabetes mellitus. In: Handbook of Diabetes. Cambridge University Press. Livingston: Blackwell Science; 1998. p. 14-18.

Sabino-Silva R, Freitas HS, Lamers ML, Okamoto MM, Santos MF, Machado UF. Na+-glucose cotransporter SGLT1 protein in salivary glands: Potential involvement in the diabetes-induced decrease in salivary flow. J Membr Biol. 2009;228(2):63-9. https://doi.org/10.1007/s00232-009-9159-3 PMid:19238474 DOI: https://doi.org/10.1007/s00232-009-9159-3

Anderson LC. Effects of alloxan diabetes and insulin in vivo on rat parotid gland. Am J Physiol. 1983;245(3):431-7. https://doi.org/10.1152/ajpgi.1983.245.3.G431 PMid:6193714 DOI: https://doi.org/10.1152/ajpgi.1983.245.3.G431

Anderson LC. Parotid gland function in streptozotocin-diabetic rats. J Dent Res. 1987;66(2):425-9. https://doi.org/10.1177/00220345870660020701 PMid:2442217 DOI: https://doi.org/10.1177/00220345870660020701

Isola M, Solinas P, Proto E, Cossu M, Lantini MS. Reduced statherin reactivity of human submandibular gland in diabetes. Oral Dis. 2011;17(2): 217-20. https://doi.org/10.1111/j.1601-0825.2010.01725.x PMid:20796227 DOI: https://doi.org/10.1111/j.1601-0825.2010.01725.x

Kwon YB, Kim HW, Rom DH. Topical application of epidermal growth factor accelerates wound healing by myofibroblast proliferation and collagen synthesis in rat. J Vet Sei. 2006;7(2):105-11. https://doi.org/10.4142/jvs.2006.7.2.105 PMid:16645332 DOI: https://doi.org/10.4142/jvs.2006.7.2.105

Cohen S. Isolation of a mouse submaxillary gland protein accelerating incisor eruption and eyelid opening in the new-born animal. J Biol Chem. 1962;237:1555-62. PMid:13880319 DOI: https://doi.org/10.1016/S0021-9258(19)83739-0

Dawson JP, Berger MB, Lin CC, Schlessinger J, Lemmon MA, Ferguson KM. Epidermal growth factor receptor dimerization and activation require ligand-induced conformational changes in the dimer interface. Mol Cell Biol. 2005;25(17):7734-42. https://doi.org/10.1128/MCB.25.17.7734-7742.2005 PMid:16107719 DOI: https://doi.org/10.1128/MCB.25.17.7734-7742.2005

Mansy M, Soliman M, Mubarak R, Shamel M. The role of exogenous epidermal growth factor on Ki-67 proliferation marker expression in the submandibular salivary gland of albino rats receiving doxorubicin. F1000Res. 2020;9:1393. https://doi.org/10.12688/f1000research.27186.1 PMid:33456767 DOI: https://doi.org/10.12688/f1000research.27186.1

Fallon JH, Seroogy KB, Loughlin SE, Morrison RS, Bradshaw RA, Knaver DJ, et al. Epidermal growth factor immunoreactive material in the central nervous system: Location and development. Science. 1984:224(4653):1107-9. https://doi.org/10.1126/science.6144184 PMid:6144184 DOI: https://doi.org/10.1126/science.6144184

Pollard TD, Korn ED. Acanthamoeba myosin. I. Isolation from Acanthamoeba castellanii of an enzyme similar to muscle myosin. J Biol Chem. 1973;248(13):4682-90. PMid:4268863 DOI: https://doi.org/10.1016/S0021-9258(19)43718-6

Sebe-Pedros A, Grau-Bove X, Richards TA, Ruiz-Trillo I. Evolution and classification of myosins, a paneukaryotic wholegenome approach. Genome Biol Evol. 2014;6(2):290-305. https://doi.org/10.1093/gbe/evu013 PMid:24443438 DOI: https://doi.org/10.1093/gbe/evu013

Ohlsson B, Jansen C, Ihse I, Axelson J. Epidermal growth factor induces cell proliferation in mouse pancreas and salivary glands. Pancreas. 1997;14(1):94-8. https://doi.org/10.1097/00006676-199701000-00014 PMid:8981513 DOI: https://doi.org/10.1097/00006676-199701000-00014

Srinivasan K, Ramarao P. Animal models in type 2 diabetes research: An overview. Indian J Med Res. 2007;125(3):451-72. PMid:17496368

Fahim MA, Hasan MY, Alshuaib WB. Cadmium modulates diabetes-induced alterations in murine neuromuscular junction. Endocr Res. 2000;26(2):205-17. https://doi.org/10.3109/07435800009066162 PMid:10921448 DOI: https://doi.org/10.3109/07435800009066162

Swearengen JR. Choosing the right animal model for infectious disease research. Animal Model Exp Med. 2018;1(2):100-8. https://doi.org/10.1002/ame2.12020 PMid:30891554 DOI: https://doi.org/10.1002/ame2.12020

Porsolt RD. Animal models of depression: Utility for transgenic research. Rev Neurosci. 2000;11(1):53-8. https://doi.org/10.1515/revneuro.2000.11.1.53 PMid:10716655 DOI: https://doi.org/10.1515/REVNEURO.2000.11.1.53

Atanasova NA. Validating animal models. Theoria. 2015;30(2):163-81. DOI: https://doi.org/10.1387/theoria.12761

Weber B, Lackner I, Haffner-Luntzer M, Palmer A, Pressmar J, Scharffetter-Kochanek K, et al. Modeling trauma in rats: Similarities to humans and potential pitfalls to consider. J Transl Med. 2019;17(1):305-10. https://doi.org/10.1186/s12967-019-2052-7 PMid:31488164 DOI: https://doi.org/10.1186/s12967-019-2052-7

Porto GG, Vasconcelos BC, Andrade ES, Silva-Junior VA. Comparison between human and rat TMJ: Anatomic and histopathologic features. Acta Cir Bras. 2010;25(3):290-3. https://doi.org/10.1590/s0102-86502010000300012 PMid:20498943 DOI: https://doi.org/10.1590/S0102-86502010000300012

Amano O, Mizobe K, Bando Y, Sakiyama K. Anatomy and histology of rodent and human major salivary glands: -Overview of the Japan salivary gland society-sponsored workshop-. Acta Histochem Cytochem. 2012;45(4):241-50. https://doi.org/10.1267/ahc.12013 PMid:23209333 DOI: https://doi.org/10.1267/ahc.12013

Anderson LC. Salivary gland structure and function in experimental diabetes. Biomed Rev. 1998;9:107-19. DOI: https://doi.org/10.14748/bmr.v9.141

Ogawa Y, Kishino M, Atsumi Y, Kimoto M, Fukuda Y, Ishida T, et al. Plasmacytoid cells in salivary-gland pleomorphic adenomas: Evidence of luminal cell differentiation. Virchows Arch. 2003;443(5):625-34. https://doi.org/10.1007/s00428-003-0890-3 PMid:14614625 DOI: https://doi.org/10.1007/s00428-003-0890-3

Dewar R, Fadare O, Gilmore H, Gown AM. Best practices in diagnostic immunohistochemistry: Myoepithelial markers in breast pathology. Arch Pathol Lab Med. 2011;135(4):422-9. https://doi.org/10.5858/2010-0336-CP.1 PMid:21466356 DOI: https://doi.org/10.5858/2010-0336-CP.1

Grandi D, Campanini N, Becchi G, Lazzaretti M. On the myoepithelium of human salivary glands. An immunocytochemical study. Eur J Morphol. 2000;38(4):249-55. https://doi.org/10.1076/0924-3860(200010)38:4;1-o;ft249 PMid:10980676 DOI: https://doi.org/10.1076/0924-3860(200010)38:4;1-O;FT249

Kasayama S, Ohba Y, Oka T. Epidermal growth factor deficiency associated with diabetes mellitus. Proc Natl Acad Sci U S A. 1989;86(19):7644-8. https://doi.org/10.1073/pnas.86.19.7644 PMid:2477846 DOI: https://doi.org/10.1073/pnas.86.19.7644

Hardwicke J, Schmaljohann D, Boyce D, Thomas D. Epidermal growth factor therapy and wound healing — past, present and future perspectives. Surgeon. 2008;6(3):172-7. https://doi.org/10.1016/s1479-666x(08)80114-x PMid:18581754 DOI: https://doi.org/10.1016/S1479-666X(08)80114-X

Rao RK, Thomas DW, Pepperl S, Porreca F. Salivary epidermal growth factor plays a role in protection of ileal mucosal integrity. Dig Dis Sci. 1997;42(10):2175-81. https://doi.org/10.1023/a:1018855525989 PMid:9365155 DOI: https://doi.org/10.1023/A:1018855525989

EL-Gusbi GA, Shredah MT, Soliman AE. Submandibular glands as an evident of the effects of antioxidant on alloxan-induced diabetic rats. World J Med Sci. 2014;11:210-6.

Tsang MW, Wong WK, Hung CS, Lai KM, Tang W, Cheung EY. Human epidermal growth factor enhances healing of diabetic foot ulcers. Diabetes Care. 2003;26(6):1856-61. https://doi.org/10.2337/diacare.26.6.1856 PMid:12766123 DOI: https://doi.org/10.2337/diacare.26.6.1856

Herbst RS. Review of epidermal growth factor receptor biology. Int J Radiat Oncol Biol Phys. 2004;59(2 Suppl):21-6. https://doi.org/10.1016/j.ijrobp.2003.11.041 PMid:15142631 DOI: https://doi.org/10.1016/j.ijrobp.2003.11.041

Hong JP, Lee SW, Song SY, Ahn SD, Shin SS, Choi EK. Recombinant epidermal growth factor treatment of radiationinduced severe oral mucositis in patients with head and neck malignancies. Eur J Cancer Care (Engl). 2009;18(6):636-41. https://doi.org/10.1111/j.1365-2354.2008.00971.x PMid:19456848 DOI: https://doi.org/10.1111/j.1365-2354.2008.00971.x

Akhtar S, Almubrad T, Bron AJ, Yousif MH, Benter IF, Akhtar S. Role of epidermal growth factor receptor (EGFR) in corneal remodeling in diabetes. Acta Ophthalmol. 2009;87(8):881-9. https://doi.org/10.1111/j.1755-3768.2008.01434.x PMid:19416119 DOI: https://doi.org/10.1111/j.1755-3768.2008.01434.x

Geng Y, Li J, Wang F, Li Q, Wang X, Sun L. Epidermal growth factor promotes proliferation and improves restoration after intestinal ischemia-reperfusion injury in rats. Inflammation. 2013;36(3):670-9. https://doi.org/10.1007/s10753-012-9591-x PMid:23397076 DOI: https://doi.org/10.1007/s10753-012-9591-x

Al-Ankily M, Shamel M, Bakr M. Epidermal growth factor and diabetes mellitus; friends or faux? Int J Med Dent Sci. 2016;5(2):1290-6. DOI: https://doi.org/10.19056/ijmdsjssmes/2016/v5i2/100625

Al-Ankily M, Shamel M, Bakr M. Epidermal growth factor improves the ultrastructure of submandibular salivary glands of streptozotocin induced diabetic rats - A qualitative study. Int J Med Dent Sci. 2020;9(1):1803-10. DOI: https://doi.org/10.18311/ijmds/2020/24452

Al-Ankily M, Shamel M, Bakr M. Epidermal growth factor restores cytokeratin expression in rats with diabetes. J Res Med Dent Sci. 2018;6(1):196-203.

Zhang K, Li Y, He J, Xu J, Wan Y, Wan S, et al. Therapeutic effect of epidermal growth factor combined with nano silver dressing on diabetic foot patients. Front Pharmacol. 2021;12:627098. https://doi.org/10.3389/fphar.2021.627098 PMid:33967761 DOI: https://doi.org/10.3389/fphar.2021.627098

Downloads

Published

2022-05-16

How to Cite

1.
Bakr M, Shamel M, Elwahed SA, Al Ankily M. A Rat Experimental Model for Investigation of the Effect of Diabetes on Submandibular Salivary Glands Treated with Epidermal Growth Factor. Open Access Maced J Med Sci [Internet]. 2022 May 16 [cited 2024 Apr. 12];10(D):190-6. Available from: https://oamjms.eu/index.php/mjms/article/view/9209

Issue

Section

Dental Pathology and Endodontics

Categories