EFFECT OF METHIMAZOLE-INDUCED HYPOTHYROIDISM ON HISTOLOGICAL CHARACTERISTICS OF PAROTID GLAND OF ALBINO RAT
AbstractBackground: The current study was carried out to investigate the effect of hypothyroidism on thehistological structure of parotid salivary gland of the rat. Methods: Twenty male albino rats, weighingbetween 130–150 grams, were used which were divided into two groups; control group (A) and anexperimental group (B), each containing 10 animals. Group B was rendered hypothyroid by givingmethimazole (MMI) as 0.02% solution in drinking water daily for 3 weeks. On day 22nd parotid andthyroid glands were removed, weighed and processed for light microscopy. Salivary gland was fixed inBouin’s solution, H&E and Toluidine blue stains were used for histological examination. Serum T3, T4and TSH levels were determined by enzyme immunoassay. Results: In group A, serum concentrationof T3, T4 and TSH was 12.58±3.05 ηg/ml, 4.72±1.20 µg/dl, and 0.25±0.24 µIU/ml respectively, whereas in group B it was 2.14±1.83 ηg/ml, 1.04±0.44 µg/dl and 1.44±0.20 µIU/ml respectively. Whendifferences between T3, T4 and TSH of the groups were compared, the p-value was <0.000, <0.000, and<0.000 respectively. Mean thyroid weight significantly increased in group B (44.1 0±1.66 mg) whencompared to that in group A (33.70±1.56 mg). These findings established the occurrence ofhypothyroid state in the experimental group. There was a statistically significant reduction in the parotidgland weight in the animals of the experimental group (38.30±1.15 mg) when compared to the controlgroup (39.60±0.84 mg), (p<0.01). With light microscopy, group A showed a normal structure ofparotid salivary gland, whereas multiple histological changes were observed in parotrid gland of theexperimental group. Number of mast cells in parotid gland was also significantly higher (p<0.017) ingroup B (3.70±1.11/mm2) than in group A (2.25±1.34/mm2). Conclusion: The level of T3, T4 decreasedand that of TSH increased in the experimental group when compared with control group; there werealso changes in the histological structure of the parotid salivary gland.Keywords: Methimazole, parotid gland, hypothyroidism, histology, rat
Milosevic M, Korac A, Davidovic V. Methimazole-induced
hypothyroidism in rats: Effects on body weight and histological
characteristics of thyroid gland. Jugoslov Med Biochem
Porth CM, Gaspard K, Guven S, Kuenzi JA, Matfin. Alterations
in pituitary, thyroid, parathyroid and adrenal function. In: Stead
L, Kogut H, Cann M, Rainey S, Schiff D, Kors E, editors.
Essentials of pathophysiology concept of altered health status. 6th
ed. USA: Lippincott Williams and Wilkins; 2004. p. 538–59.
Oncu M, Kanter M, Gokcimen A, Kavakli D, Oncu M, Ural M et
al. Effect of thyroidectomy on the histology of rat sublingual
gland. APMIS 2004;112:119–22.
J Ayub Med Coll Abbottabad 2010;22(3)
Green Span FS, Dong BJ. Thyroid and anti-thyroid drugs. In:
Katzung BG, editor. Basic and clinical pharmacology. 9thed.
USA: Mc Graw Hill; 2004. p. 625–40.
Kimura T, Furudate S. Pituitary GH and prolactin deficiency and
testis enlargement in hypothyroid rats caused by goitrogen
methimazole. Exp Anim 1996;45(4):369–75.
Chiao YC, Lee HY, Wang SW, Hwang JJ, Chien CH, Huang
SW et al. Regulation of thyroid hormones on the production of
testosterone in rats. J Cell Biochem 1999;73(4):554–62.
Antony FF, Aruldhas MM, Udhayakumar RC, Maran RR,
Govindarajulu P. Inhibition of leydig cell activity in vivo and in
vitro in hypothyroid rats. J Endocrinol 1995;144(2):293–300.
Duntas LH. Thyroid disease and lipids. Thyroid
Caraccio N, Ferrannini E, Monzani F. Lipoprotein profile in
subclinical hypothyroidism: Response to levothyroxine
replacement, a randomized placebo-controlled study. J Clin
Endocrinol Metab 2002;87(4):1533–8.
Pucci E, Chiovato L, Pinchera A. Thyroid and lipid metabolism.
Int Obes Relat Metab Disord 2000;24(2):109–12.
Fulop M. Pouting Sublinguals: Enlarged Salivary Glands in
Myxoedema. Lancet 1989;2(8662):550–1.
Ogilvie AL. Histological findings in the salivary glands of the rat
following sodium fluoride administration. J D Res
Ashour MA. Long-term effect of melatonin on submandibular
salivary glands in old rats. Eastern Mediterranean Health J
Ewens AD, Mihich E, Ehrke MJ. Fluorouracil plus leucovorin
induces submandibular salivary gland enlargement in rats.
Toxicologic Pathology 2005;33(4):507–15.
Jhee HT, Han SS, Avery JK. A study of salivary glands of rats
injected with actinomycin D. American J Anatomy
Bixler D, Webster RC, Muhler JC. The effect of testosterone,
thyroxine, and cortisone on the salivary glands of the
hypophysectomized rat. J D Res 1956;36(4):566–70.
Jezek D, Banek L, Panijan RP, Pezerovic D. Quantitative study
on the rat parotid gland after orchiectomy. Veterinarski Arhiv
Leal SC, Toledo OA, Bezerra ACB. Morphological alterations of
the parotid gland of rats maintained on liquid diet. Braz Dent J
Tanaka K and Imura H. Iodothyronine 5’-deiodinase is present in
mouse sublingual gland. Endocrinology 1993;132(3):1195–8.
Hiramatsu M, Kashimata M, Kumegawa M, Minami N.
Suppression by thyroid hormones of glucosamine-6-phosphate
synthetase activity in rat sublingual glands. Arch Oral Biol
Ostuni MA, Houssay AB, Tumilasci OR. Modulation by thyroid
hormones of rat parotid amylase secretion stimulated by 5-
hydroxytryptamine. Eur J Oral Sci 2003;111:492–6.
Gomes GMP, Albuquerque JPG, Ferra MA. Serotonin and
gastrin cells in rat gastrointestinal tract after
thyroparathyroidectomy and induced hyperthyroidism. Dig Dis
Coll J, Anglada J, Tomas S, Reth P, Goday A, Millan M et al.
High prevalence of subclinical sjogren’s syndrome features in
patients with autoimmune thyroid disease . J Rheumatol
Hansen BU, Ericsson UB, Henricsson V, Larsson A, Manthorpe
R, Warfvinge G. Autoimmune thyroiditis and primary sjogren’s
syndrome: clinical and laboratory evidence of the coexistence of
the two diseases. Clin Exp Rheumatol 1991;9(2):137–41.
Olver IN. Xerostomia: a common adverse effect of drugs and
radiation. Aust Prescr 2006;29:97–8.
Haldi J, Wynn W, Law ML. Relationship between thyroid
function and resistance to dental caries. J Dent Res
Ozen A, Ergun L, Ergun E, Simsek N. Morphological studies on
Ovarian Mast Cells in the Cow. Turk J Vet Anim Sci
Bhargava HN, Ramarao P, Gulati A. Effect of methimazoleinduced hypothyroidism on multiple opioid receptors in rat brain
regions. Pharmacology 1988;37(6):356–64.
Isman CA, Yegen BC, Alican I. Methimazole-induced
hypothyroidism in rats ameliorates oxidative injury in
experimental colitis. J Endocr 2003;177:471–6.
Kala N, Ravisankar B, Govindarajulu P, Aruldhas MM. Impact
of foetal-onset hypothyroidism on the epididymis of mature rats.
Int J Androl 2002;25(3):139–48.
Oren R, Hilzenrat N, Maaravi Y, Yaari A, Sikuler E.
Hemodynamic effects of hypothyroidism induced by
methimazole in normal and portal hypertensive rats. Digestive
diseases and sciences 1995;40(9):1941–5.
Oren R, Dotan I, Brill S, Jones BE, BenHaim M, Sikuler E,
Halpern Z. Altered thyroid status modulates portal pressure in
normal rats. Liver 1999;19(5):423–6.
Karaca T, Yoruk M. A Morphological and Histometrical study
on Distribution and Heterogeneity of Mast Cells of Chicken’s
and Quail’s Digestive Tract. YYU Vet Fak Derg 2004;15(1-
Saglam B, Cikler E, Zeybek A, Cetinel S, Ercan F, Sener G.
Protective effects of 2-Mercaptoethane Sulfonate (MESNA) on
Protamine Sulfate induced bladder damage. Marmara Medical J