CC BY 4.0 · Eur J Dent 2023; 17(03): 678-686
DOI: 10.1055/s-0042-1744372
Original Article

Comparative Study of Cytokeratin Immunostaining of Parotid Gland Parenchyma in Normal, Diabetic, and Excretory Duct Ligation of Mongrel Dogs

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


Objectives The present study aimed to give a glimpse of the normal distribution of intermediate filaments within the parotid gland parenchyma of mongrel dogs and to reveal the pathological changes that may occur as a result of the effects of diabetes mellitus or atrophy of the gland caused by the ligation of the excretory duct to discover whether there is a similarity in these pathological behaviors.

Materials and Methods Twelve healthy mongrel dogs were used in the experiment and were divided into three groups: group I (the control group), group II (dogs with alloxan-induced diabetes), and group III (dogs with the right-side duct-ligated parotid gland). The dogs were sacrificed 45 days after the parotid excretory duct were tied. The right parotid gland of all groups was dissected and prepared for histological and immunohistochemical expression of cytokeratin 17 assay.

Results Histological findings confirmed that the parotid gland parenchyma of the diabetic group had glandular atrophy characterized by the loss of gland structure, degenerated acini, and dilatation of the duct system. Moreover, there is a predominance of the fibrous component with the presence of fat cells within the gland compartments. On the contrary, the excretory duct-ligated group undergoes severe glandular atrophy of the previous character with the presence of duct-like structure as well as extravasation and vasodilatation. Immunohistochemical expression of cytokeratin 17 in control parotid using an immunoperoxidase technique showed that cytokeratin expression varies from negative to mild in all ducts and some serous acinar cells. The gland parenchyma of the diabetic group showed mild to strong cytokeratin expression of duct cells more concentrated in the apical part with moderate to strong expression of diffuse type in some serous acini. The intensity of cytokeratin 17 in gland compartments of the excretory duct-ligated group revealed a variation in expression that ranged from negative to strong diffuse staining throughout the gland.

Conclusion The severity and prevalence of cytokeratin 17 in our results are predictive of the pathological influence of both diabetes mellitus and duct ligation on the cytokeratin intracellular filaments of the salivary gland parenchyma in a different way that interferes with saliva production and/or secretion leading to xerostomia.

Publication History

Article published online:
21 June 2022

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  • References

  • 1 Mahmoud A, Sherif SH. Expression of cytokeratin, actin and proliferating cell nuclear antigen (PCNA) in parotid gland of normal and alloxan-induced diabetic dogs. (Histological and immunohisto-chemical study). Cairo Dent J 2015; 31 (02) 2661-2674
  • 2 Dodds MW, Johnson DA, Yeh CK. Health benefits of saliva: a review. J Dent 2005; 33 (03) 223-233
  • 3 Schipper RG, Silletti E, Vingerhoeds MH. Saliva as research material: biochemical, physicochemical and practical aspects. Arch Oral Biol 2007; 52 (12) 1114-1135
  • 4 Maria OM, Maria SM, Redman RS. et al. Effects of double ligation of Stensen's duct on the rabbit parotid gland. Biotech Histochem 2014; 89 (03) 181-198
  • 5 Gaber W, Shalaan S, Misk N, Ibrahim A. Surgical anatomy, morphometry, and histochemistry of major salivary glands in dogs: updates and recommendations. Int J Vet Health Sci Res 2020; 8 (02) 252-259
  • 6 Wang S, Marchal F, Zou Z, Zhou J, Qi S. Classification and management of chronic sialadenitis of the parotid gland. J Oral Rehabil 2009; 36 (01) 2-8
  • 7 de Almeida PdelV, Grégio AM, Machado MA, de Lima AA, Azevedo LR. Saliva composition and functions: a comprehensive review. J Contemp Dent Pract 2008; 9 (03) 72-80
  • 8 Correia PN, Carpenter GH, Osailan SM, Paterson KL, Proctor GB. Acute salivary gland hypofunction in the duct ligation model in the absence of inflammation. Oral Dis 2008; 14 (06) 520-528
  • 9 Neyraud E, Dransfield E. Relating ionisation of calcium chloride in saliva to bitterness perception. Physiol Behav 2004; 81 (03) 505-510
  • 10 Gandara BK, Morton TH. Non-periodontal oral manifestations of diabetes: a framework for medical care providers. Diabetes Spectr 2011; 24: 199-205
  • 11 Sherif SH, Mahmoud A. Effect of fractionated irradiation on rat lingual salivary glands (histopathological and immunohistochemical study). Azhar Journal of Dental Science 2008; 11 (01) 23-30
  • 12 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
  • 13 Unger J, Parkin CG. Type 2 diabetes: an expanded view of pathophysiology and therapy. Postgrad Med 2010; 122 (03) 145-157
  • 14 Deconte SR, Oliveira RJ, Calábria LK. et al. Alterations of antioxidant biomarkers and type I collagen deposition in the parotid gland of streptozotocin-induced diabetic rats. Arch Oral Biol 2011; 56 (08) 744-751
  • 15 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
  • 16 Zowgar AM, Siddiqui MI, Alattas KM. Level of diabetes knowledge among adult patients with diabetes using diabetes knowledge test. Saudi Med J 2018; 39 (02) 161-168
  • 17 Alluqmani WS, Alotaibi MM, Almalki WJ. et al. Exploring drug-related problems in diabetic patients during Ramadan fasting in Saudi Arabia: a mixed-methods study. Int J Environ Res Public Health 2019; 16 (03) 499
  • 18 Aldahlawi S, Nourah D, Andreana S. Should quality of glycemic control guide dental implant therapy in patients with diabetes? Focus on: peri-implant diseases. Clin Cosmet Investig Dent 2021; 13: 149-154
  • 19 Lenzen S. The mechanisms of alloxan- and streptozotocin-induced diabetes. Diabetologia 2008; 51 (02) 216-226
  • 20 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
  • 21 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
  • 22 Chavez EM, Taylor GW, Borrell LN, Ship JA. Salivary function and glycemic control in older persons with diabetes. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000; 89 (03) 305-311
  • 23 Gupta N, Gupta ND, Gupta A, Goyal L, Garg S. The influence of type 2 diabetes mellitus on salivary matrix metalloproteinase-8 levels and periodontal parameters: a study in an Indian population. Eur J Dent 2015; 9 (03) 319-323
  • 24 Siudikiene J, Machiulskiene V, Nyvad B, Tenovuo J, Nedzelskiene I. Dental caries and salivary status in children with type 1 diabetes mellitus, related to the metabolic control of the disease. Eur J Oral Sci 2006; 114 (01) 8-14
  • 25 Cummins M, Dardick I, Brown D, Burford-Mason A. Obstructive sialadenitis: a rat model. J Otolaryngol 1994; 23 (01) 50-56
  • 26 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
  • 27 Qi S, Liu X, Wang S. Sialoendoscopic and irrigation findings in chronic obstructive parotitis. Laryngoscope 2005; 115 (03) 541-545
  • 28 Giger R, Mhawech P, Marchal F, Lehmann W, Dulguerov P. Mucoepidermoid carcinoma of Stensen's duct: a case report and review of the literature. Head Neck 2005; 27 (09) 829-833
  • 29 Jinhua Z, Changling D, Yuhong Z. et al. Biological changes of myoepithelial cells in atrophic glands after ligation of parotid duct. Int J Clin Exp Pathol 2016; 9 (08) 8478-8484
  • 30 Mulyani SWM, Astuti ER, Wahyuni OR, Ernawati DS, Ramadhani NF. Xerostomia therapy due to ionized radiation using preconditioned bone marrow-derived mesenchymal stem cells. Eur J Dent 2019; 13 (02) 238-242
  • 31 Kyriacou K, Garrett JR. Morphological changes in the rabbit submandibular gland after parasympathetic or sympathetic denervation. Arch Oral Biol 1988; 33 (04) 281-290
  • 32 Carpenter GH, Osailan SM, Correia P, Paterson KP, Proctor GB. Rat salivary gland ligation causes reversible secretory hypofunction. Acta Physiol (Oxf) 2007; 189 (03) 241-249
  • 33 Scott J, Liu P, Smith PM. Morphological and functional characteristics of acinar atrophy and recovery in the duct-ligated parotid gland of the rat. J Dent Res 1999; 78 (11) 1711-1719
  • 34 Harrison JD, Fouad HM, Garrett JR. The effects of ductal obstruction on the acinar cells of the parotid of cat. Arch Oral Biol 2000; 45 (11) 945-949
  • 35 Miguel MC, Andrade ES, Taga R, Pinto LP, Souza LB. Hyperplasia of myoepithelial cells expressing calponin during atrophy of the rat parotid gland induced by duct ligation. Histochem J 2002; 34 (10) 499-506
  • 36 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
  • 37 Robar JL, Day A, Clancey J. et al. Spatial and dosimetric variability of organs at risk in head-and-neck intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys 2007; 68 (04) 1121-1130
  • 38 Elabasiry M, Hassan SS, Altohamy SM. Expression of cytokeratin 17 in normal and diabetic submandibular salivary gland (histological and immunohistochemical study). Tanta Dental J 2018; 15: 241-246
  • 39 Sozmen M, Brown PJ, Eveson JW. Cytokeratin immunostaining in normal dog major and minor salivary glands. Vet Res 1998; 29 (05) 457-465
  • 40 Kim JM, Chung JY, Lee SY. et al. Hypoglycemic effects of vanadium on alloxan monohydrate induced diabetic dogs. J Vet Sci 2006; 7 (04) 391-395
  • 41 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
  • 42 Dawson LJ, Fox PC, Smith PM. Sjogrens syndrome—the non-apoptotic model of glandular hypofunction. Rheumatology (Oxford) 2006; 45 (07) 792-798
  • 43 Bartel-Friedrich S, Friedrich R, Lautenschlager C, Moll R, Holzhausen H. Dose-response relationships on the expression profile of cytokeratins and vimentin in rats following fractionated irradiation. Anticancer Res 2000; 20: 4917-4926