Effects of diabetes on the post-menopausal rat sublingual glands: A histopathological and stereological examination

Başak BÜYÜK, Seçil Nazife PARLAK, Osman Nuri KELEŞ, Jale SELLİ, Elif POLAT, Bünyami ÜNAL
1.660 321


Menopause is a physiological process of ovarian and uterine cycles related with decreasing of steroidal estrogen hormone level that decreases or terminates generally after 45 years old in women. Diabetes Mellitus (DM) is a metabolic disease that is defined high blood glucose level that goes on over a prolonged period due to insufficient insulin secretion. The goal of the study is to observe the effects of diabetes on postmenopausal rat sublingual glands that causes pathophysiological processes because salivary glands are sensitive to estrogen. Adult female 12 weeks old Sprague Dawley rats (n=24) were divided into four groups in a random manner; healthy control group, diabetes induced group, ovariectomized group (OVX), post ovariectomy diabetes induced group (DM+OVX). To evaluate the findings histopathological, histochemical and stereological analysis were achieved. In DM group degenerative serous demilune and duct cells, in OVX group increased polymorphonuclear leukocyte (PMNL) infiltration and in DM+OVX group extensive and increased PMNL infiltration, degenerative serous demilunes and increase in the serous demilune thickness were distinguished. Alterations in the content and amount of neutral mucopolysaccharidosis secretion of serous demilunes in DM or DM+OVX groups and acidic mucopolysaccharidosis secretion of mucous acinus in DM and/or OVX groups were detected. In addition, stereological analysis revealed that hypertrophic changes in DM groups and atrophic changes in OVX groups were occurred in the mucous acinus epithelium. The results suggest that diabetes and/or ovariectomy triggered pathophysiological processes that caused morphological and functional changes at the cellular level in sublingual glands. Molecular mechanism and relation to glucose and lipid metabolisms of pathophysiological processes in the sublingual gland in DM and OVX groups require further investigation.


Diabetes; menopause; rats; sublingual gland

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Albayrak, A., Uyanik, M. H., Odabasoglu, F., Halici, Z., Uyanik, A., Bayir, Y., Albayrak, F., Albayrak, Y., Polat, B., Suleyman, H., 2011. The effects of diabetes and/or polymicrobial sepsis on the status of antioxidant enzymes and pro-inflammatory cytokines on heart, liver, and lung of ovariectomized rats. J. Surg. Res. 169, 67-75.

Anderson, L. C., Garrett, J. R., 1986. Lipid accumulation in the major salivary glands of streptozotocin-diabetic rats. Arch. Oral. Biol. 31, 469- 475.

Calvin, M., 2002. Ovarian hormone deficiency and wound healing. In: International Congress Series, pp. 179-185. Elsevier.

Halici, Z., Bilen, H., Albayrak, F., Uyanik, A., Cetinkaya, R., Suleyman, H., Keles, O.N., Unal, B., 2009. Does telmisartan prevent hepatic fibrosis in rats with alloxan-induced diabetes? Eur. J. Pharmacol. 614, 146-152. doi:10.1016/j.ejphar. 2009.04.042.

Iaremenko, A., Kutukova, S., 2007. Experimental substantiation of hormone replacing therapy by estrogens in treatment and prevention of inflammatory infectious diseases of maxillo-facial region. Stomatologiia. 86, 13.

Ibuki, F.K., Simoes, A., Nogueira, F.N., 2010. Antioxidant enzymatic defense in salivary glands of streptozotocin-induced diabetic rats: A temporal study. Cell Biochem. Funct. 28, 503-508. doi:10.1002/cbf.1683.

Kamata, M., Shirakawa, M., Kikuchi, K., Matsuoka, T., Aiyama, S., 2007. Histological analysis of the sublingual gland in rats with streptozotocin- induced diabetes. Okajimas. Folia. Anat. Jpn. 84, 71-76.

Keles, M., Tozoglu, U., Unal, D., Caglayan, F., Uyanik, A., Emre, H., Cayir, K., Aydinli, B., 2011. Exfoliative cytology of oral mucosa in kidney transplant patients: A cytomorphometric study. In: Transplantation proceedings, Elsevier. pp. 871-875.

Maekawa, E.T., Maioral, E.E., Metidieri, H.T., Picardi, P.K. , Caldeira, E.J., 2011. Recovery of INS-R and ER-alpha expression in the salivary glands of diabetic mice submitted to hormone replacement therapy. Arch Oral Biol 56, 1129-1136. doi:10.1016/j.archoralbio.2011.03.014.

Mahay, S., Adeghate, E., Lindley, M., Rolph, C., Singh, J., 2004. Streptozotocin-induced type 1 diabetes mellitus alters the morphology, secretory function and acyl lipid contents in the isolated rat parotid salivary gland. Mol. Cell Biochem 261, 175-181.

Mainini, G., Rotondi, M., Di Nola, K., Pezzella, M., Iervolino, S., Seguino, E., D’Eufemia, D., Iannicelli, I., Torella, M., 2011. Oral supplementation with antioxidant agents containing alpha lipoic acid: Effects on postmenopausal bone mass. Clin. Exp. Obst. Gynec. 39, 489-493.

Mann, V., Huber, C., Kogianni, G., Collins, F., Noble, B., 2007. The antioxidant effect of estrogen and selective estrogen receptor modulators in the inhibition of osteocyte apoptosis in vitro. Bone. 40, 674-684.

Mattfeldt, T., Mall, G., Gharehbaghi, H., Moller, P., 1990. Estimation of surface area and length with the orientator. J Microsc. 159, 301-317.

Meurman, J.H., Tarkkila, L., Tiitinen, A., 2009. The menopause and oral health. Maturitas 63, 56-62. doi:10.1016/j.maturitas.2009.02.009.

Morris, P.A., Prout, R.E., Proctor, G.B., Garrett, J.R., Anderson, L.C., 1992. Lipid analysis of the major salivary glands in streptozotocin-diabetic rats and the effects of insulin treatment. Arch. Oral. Biol. 37, 489-494.

Nyengaard, J.R., Gundersen, H.J.G., 1992. The isector: A simple and direct method for generating isotropic, uniform random sections from small specimens. J Microsc. 165, 427-431.

Parlak, S.N., Tatar, A., Keles, O.N., Selli, J., Can, I., Unal, B., 2014. Effects of menopause and diabetes on the rat parotid glands: A histopathological and stereological study. Int. J. Med. Sci. Public Health. 3, 749-755.

Perkins, B.A., Rabbani, N., Weston, A., Ficociello, L.H., Adaikalakoteswari, A., Niewczas, M., Warram, J., Krolewski, A.S., Thornalley, P., 2012. Serum levels of advanced glycation endproducts and other markers of protein damage in early diabetic nephropathy in type 1 diabetes. PLoS One. 7, e35655. doi:10.1371/journal.pone.0035655.

Purushotham, K.R., Wang, P.L., Dolce, C., Zelles, T., Blazsek, J., Humphreys-Beher, M.G., 1993. Effects of surgical ovariectomy on rat salivary gland function. Arch. Oral. Biol. 38, 779-784.

Streckfus, C.F., Baur, U., Brown, L.J., Bacal, C., Metter, J., Nick, T., 1998. Effects of estrogen status and aging on salivary flow rates in healthy Caucasian women. Gerontology. 44, 32-39.

Subbiah, M., Kessel, B., Agrawal, M., Rajan, R., Abplanalp, W., Rymaszewski, Z., 1993. Antioxidant potential of specific estrogens on lipid peroxidation. J. Clin. Endo. Met. 77, 1095-1097.

Surmeli, M., Habesoglu, T.E., Habesoglu, M., Deveci, I., Eriman, M., Kinis, V., Gunes, P., Egeli, E., 2011. Histopathological effects of estrogen deficiency on larynx mucosa in ovariectomised rats. Eur. Arch. Oto-Rhino-Lary. 268, 261-266.

Turner, S., Zettler, G., Arcos, M.L., Cremaschi, G., Davicino, R., Anesini, C., 2011. Effect of streptozotocin on reactive oxygen species and antioxidant enzyme secretion in rat submandibulary glands: A direct and an indirect relationship between enzyme activation and expression. Eur. J. Pharmacol. 659, 281-288. doi:10.1016/j.ejphar.2011.03.015.

Unal, D., Aksak, S., Halici, Z., Sengul, O., Polat, B., Unal, B., Halici, M., 2011. Effects of diabetes mellitus on the rat liver during the postmenopausal period. J. Mol. Histol. 42, 273-287. doi:10.1007/s10735-011-9331-9.

Valimaa, H., Savolainen, S., Soukka, T., Silvoniemi, P., Makela, S., Kujari, H., Gustafsson, J., Laine, M., 2004. Estrogen receptor-beta is the predominant estrogen receptor subtype in human oral epithelium and salivary glands. J. Endoc. 180, 55-62.

Yashida, M.H., Da Silva Faria, A.L., Caldeira, E.J., 2011. Estrogen and insulin replacement therapy modulates the expression of insulin-like growth factor-I receptors in the salivary glands of diabetic mice. Anat. Rec. (Hoboken). 294, 1930-1938. doi:10.1002/ar.21481.