CC BY 4.0 · Eur J Dent 2023; 17(02): 485-491
DOI: 10.1055/s-0042-1749159
Original Article

Immunohistochemical Evaluation of the Pathological Effects of Diabetes Mellitus on the Major Salivary Glands of Albino Rats

Mashael Saeed Alqahtani
1   Division of Oral Pathology, Department of Basic and Clinical Oral Sciences, Faculty of Dentistry, Umm Al-Qura University, Makkah, Kingdom of Saudi Arabia
2   Department of Oral Biology and Dental Anatomy, Faculty of Dentistry, Al-Azhar University, Assiut, Egypt
3   Division of Oral Biology, Department of Basic and Clinical Oral Sciences, Faculty of Dentistry, Umm Al-Qura University, Makkah, Kingdom of Saudi Arabia
› Author Affiliations


Objectives Diabetes mellitus is a notorious chronic disease characterized by hyperglycemia. Our study aimed to determine the expression of cytokeratin 17 (CK17) in all major salivary glands of diabetic albino rats to provide more information about the pathological effects of DM on the intracellular structures of the gland parenchyma.

Materials and Methods Twenty male adult albino rats were utilized in the experiment and divided into two equal groups, group 1 (control rats) and group 2 (diabetic rats). The animals were sacrificed 45 days after diabetes induction. The major salivary gland complex of all groups was dissected and prepared for evaluation by histological and immunohistochemical expression of CK17.

Results Histological results prove that the salivary gland parenchyma of diabetic group undergo gland atrophy characterized with the presence of degenerated acini, dilated duct system, and presence of duct-like structure with predominance of fibrous tissue compartment and discrete fat cells. Immunohistochemical expression of CK17 of major salivary gland of control group revealed negative to diffuse mild expression in all duct cells and some serous acinar cells, whereas mucous acini were negatively stained. On the other hand, major salivary gland parenchyma of diabetic group demonstrated mild to strong expression of duct cells more concentrated at their apical part with moderate to strong expression of some serous acini of diffuse type, whereas mucous acini of both submandibular gland and sublingual gland were negatively stained.

Conclusion The severity and prevalence of CK 17 in our results are predictive of the pathological influence of the DM that interferes with saliva production and/or secretion leading to dry mouth. The results also showed clear changes in the cytokeratin expression of diabetic sublingual salivary gland, although it had little effect in the routine histological study with hematoxylin and eosin, confirming that routine studies are not sufficient to form a definitive opinion.

Publication History

Article published online:
04 July 2022

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  • References

  • 1 Mahmoud A, Sherif S. Expression of cytokeratin, actin and proliferating cell nuclear antigen (PCNA) in parotid gland of normal and alloxan-induced diabetic dogs. (Histological and immunohistochemical study). Cairo Dent J 2015; 31 (02) 2661-2674
  • 2 Hand AR, Pathmanathan D, Field RB. Morphological features of the minor salivary glands. Arch Oral Biol 1999; ;44 Suppl 1: S3-10
  • 3 Mednieks MI, Szczepanski A, Clark B, Hand AR. Protein expression in salivary glands of rats with streptozotocin diabetes. Int J Exp Pathol 2009; 90 (04) 412-422
  • 4 Sara Y, Ahmed A. Histomorphometric and immunohistochemical study comparing the effect of diabetesmellitus on the acini of the sublingual and submandibular salivary glands of albino rats. J Med Sci 2020; 8(A): 49-54
  • 5 Lydiatt DD, Bucher GS. The historical evolution of the understanding of the submandibular and sublingual salivary glands. Clin Anat 2012; 25 (01) 2-11
  • 6 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 (05) 241-250
  • 7 Unger J, Parkin CG. Type 2 diabetes: an expanded view of pathophysiology and therapy. Postgrad Med 2010; 122 (03) 145-157
  • 8 Stewart CR, Obi N, Epane EC. et al. The Effects of diabetes on salivary gland protein expression of tetrahydrobiopterin and nitric oxide synthesis and function. J Periodontol 2016; 87 (06) 735-741
  • 9 Heji ES, Bukhari AA, Bahammam MA, Homeida LA, Aboalshamat KT, Aldahlawi SA. Periodontal disease as a predictor of undiagnosed diabetes or prediabetes in dental patients. Eur J Dent 2021; 15 (02) 216-221
  • 10 Hassan SS, Alqahtani MS. Comparative study of cytokeratin immunostaining of parotid gland parenchyma in normal, diabetic and excretory duct ligation of Mongrel dogs. Eur J Dent 2022; DOI: 10.1055/s-0042-1744372.
  • 11 Baltzis D, Eleftheriadou I, Veves A. Pathogenesis and treatment of impaired wound healing in diabetes mellitus: new insights. Adv Ther 2014; 31 (08) 817-836
  • 12 Akinbami BO, Godspower T. Dry socket: incidence, clinical features, and predisposing factors. Int J Dent 2014; 2014: 796102
  • 13 Ranjan R, Rajan S. Oral healthmanifestations in diabetic patients – a review. Int J Community Health Med Res 2016; 2: 58-62
  • 14 Gandara BK, Morton TH. Non-periodontal oral manifestations of diabetes; a framework formedical care providers. Diabetes Spectr 2001; 24: 199-205
  • 15 Stewart CR, Obi N, Epane EC. et al. Effects of diabetes on salivary gland protein Expression of tetrahydrobiopterin and nitric oxide synthesis and function. J Periodontol 2016; 87 (06) 735-741
  • 16 Mata AD, Marques D, Rocha S. et al. Effects of diabetes mellitus on salivary secretion and its composition in the human. Mol Cell Biochem 2004; 261 (1–2): 137-142
  • 17 Caldeira EJ, Camilli JA, Cagnon VH. Stereology and ultrastructure of the salivary glands of diabetic Nod mice submitted to long-term insulin treatment. Anat Rec A Discov Mol Cell Evol Biol 2005; 286 (02) 930-937
  • 18 Carda C, Mosquera-Lloreda N, Salom L, Gomez de Ferraris ME. Peydró A Structural and functional salivary disorders in type 2 diabetic patients. Med Oral Patol Oral Cir Bucal 2006; 11 (04) E309-E314
  • 19 Sreebny LM, Yu A, Green A, Valdini A. Xerostomia in diabetes mellitus. Diabetes Care 1992; 15 (07) 900-904
  • 20 Anderson LC. Effects of alloxan diabetes and insulin in vivo on rat parotid gland. Am J Physiol 1983; 245 (03) G431-G437
  • 21 Hand AR, Weiss RE. Effects of streptozotocin-induced diabetes on the rat parotid gland. Lab Invest 1984; 51 (04) 429-440
  • 22 Anderson LC, Suleiman AH, Garrett JR. Morphological effects of diabetes on the granular ducts and acini of the rat submandibular gland. Microsc Res Tech 1994; 27 (01) 61-70
  • 23 Anderson LC, Garrett JR. Lipid accumulation in the major salivary glands of streptozotocin-diabetic rats. Arch Oral Biol 1986; 31 (07) 469-475
  • 24 Piras M, Hand AR, Mednieks MI, Piludu M. Amylase and cyclic amp receptor protein expression in human diabetic parotid glands. J Oral Pathol Med 2010; 39 (09) 715-721
  • 25 Berkovitz BK, Holland GR, Moxham BJ. Oral Anatomy, Histology and Embryology. 5th ed.. London/Philadelphia/Toronto: Mosby; 2017: 225-267
  • 26 Herrmann H, Aebi U. Intermediate filaments: structure and assembly. Cold Spring Harb Perspect Biol 2016; 8 (11) a018242
  • 27 Alan S, James S. Human Histology. 2nd ed. London; Baltimore: Mosby; 1997: 23-26
  • 28 Hassan SS, Attia MA, Attia AM, Nofal RA, Fathi A. Distribution of cytokeratin 17 in the parenchymal elements of rat's submandibular glands subjected to fractionated radiotherapy. Eur J Dent 2020; 14 (03) 440-447
  • 29 Sabino-Silva R, Okamoto MM, David-Silva A, Mori RC, Freitas HS, Machado UF. Increased SGLT1 expression in salivary gland ductal cells correlates with hyposalivation in diabetic and hypertensive rats. Diabetol Metab Syndr 2013; 5 (01) 64-69
  • 30 Harrison JD, Epivatianos A, Bhatia SN. Role of microliths in the aetiology of chronic submandibular sialadenitis: a clinicopathological investigation of 154 cases. Histopathology 1997; 31 (03) 237-251
  • 31 Takahashi S, Shinzato K, Domon T, Yamamoto T, Wakita M. Proliferation and distribution of myoepithelial cells during atrophy of the rat sublingual gland. J Oral Pathol Med 2003; 32 (02) 90-94
  • 32 Makino I, Murakami Y, Murakami M, Saito Y, Wada Y, Nishiyama Y. An immunohistological study of normal parotid gland [in Japanese]. Nippon Jibiinkoka Gakkai Kaiho 1992; 95 (12) 1923-1930