Main Article Content
Diabetes mellitus has been reported to be accompanied by thyroid and testicular dysfunctions. The objective of this study was to investigate the effect of Quercus infectoria galls (QIg) extract on the thyroid gland and testicular functions in diabetic rats. Sixteen rats were randomly divided into four equal groups, consisting of normal control, diabetic untreated control, diabetic treated with oral administration of 500 mg/kg BW and 1000 mg/kg BW, respectively for 15 days. Serum blood glucose, thyroid stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), testosterone (T), and luteinizing hormone (LH) were assessed. At the end of the experimental period, the rats were euthanized for histopathological analysis of thyroid gland and testis. Furthermore, immunohistochemistry was used to assess the expression of thyroid transcription factor-1 (TTF-1) in the thyroid gland of rats. The significant increase in serum blood glucose level in diabetic rats (DC) was markedly decreased by treatment with QIg extract (500 mg and 100 mg/kg BW) almost to the normal level. The reduced thyroid hormones, both the T3 and T4 were significantly recovered after 15 days of treatment with QIg extract (500 mg and 100 mg/kg BW). Whereas serum concentration of testosterone was significantly reduced in diabetic rats with QIg extract (500 mg and 100 mg/kg BW) treatment. Histopathological analysis of diabetic rats showed a wide range of morphological alterations in thyroid gland and testicular structures, which were almost completely, restored back to normal by treatment of rats with QIg extract. Furthermore, results showed overexpression of TTF-1 in the thyroid gland of diabetic rats, which was recovered back to normal expression after 15 days of treatment with QIg extract. These findings may provide new insights into the potential role of QIg extract as a promising therapeutic agent against diabetic complications in thyroid gland and testicular functions.
Correspondence: [email protected]
Received: 28 September 2021
Accepted: 28 November 2021
Published: 28 December 2021
This work is licensed under a Creative Commons Attribution 4.0 International License.
Mohamed NA, Abdel Gawad HS. Taurine dietary supplementation attenuates brain, thyroid, testicular disturbances and oxidative stress in streptozotocin-induced diabetes mellitus in male rats. Beni Suef Univ J Basic Appl Sci. 2017; 6: 247-252.
Hoenig M. Carbohydrate metabolism and pathogenesis of diabetes mellitus in dogs and cats. Prog Mol Biol Transl Sci. 2014; 121: 377-412.
Kadiyala R, Peter R, Okosieme OE. Thyroid dysfunction in patients with diabetes: clinical implications and screening strategies. Int J Clinl Pract. 2010; 64(8): 1130-1139.
Ninomiya T, Perkovic V, de Galan BE, Zoungas S, Pillai A, Jardine M, et al. Albuminuria and kidney function independently predict cardiovascular and renal outcomes in diabetes. J Am Soc Nephrol. 2009; 20(8): 1813-18121.
Alam S, Hasan MK, Neaz S, Hussain N, Hossain MF, Rahman T. Diabetes Mellitus: insights from epidemiology, biochemistry, risk factors, diagnosis, complications and comprehensive management. Diabetology. 2021; 2(2): 36-50.
Galicia-Garcia U, Benito-Vicente A, Jebari S, Larrea-Sebal A, Siddiqi H, Uribe KB, et al. Pathophysiology of type 2 diabetes mellitus. Int J Mol Sci. 2020; 21(17): 6275.
Muoio DM, Newgard CB. Mechanisms of disease: molecular and metabolic mechanisms of insulin resistance and beta-cell failure in type 2 diabetes. Nat Rev Mol Cell Biol. 2008; 9(3): 193-205.
Mitrou P, Raptis SA, Dimitriadis G. Insulin action in hyperthyroidism: a focus on muscle and adipose tissue. Endocr Rev. 2010; 31(5): 663-679.
Wagner MS, Wajner SM, Maia AL. The role of thyroid hormone in testicular development and function. J Endocrinol. 2008; 199(3): 351-365.
Potenza M, Via MA, Yanagisawa RT. Excess thyroid hormone and carbohydrate metabolism. Endocr Pract. 2009; 15(3): 254-262.
Chiamolera MI, Wondisford FE. Minireview: Thyrotropin-releasing hormone and the thyroid hormone feedback mechanism. Endocrinology. 2009; 150(3): 1091-1096.
Wang C. The Relationship between type 2 diabetes mellitus and related thyroid diseases. J Diabetes Res. 2013; 2013: 390534.
Akbar DH, Ahmed MM, Al-Mughales J. Thyroid dysfunction and thyroid autoimmunity in Saudi type 2 diabetics. Acta Diabetol. 2006; 43(1): 14-18.
Hage M, Zantout MS, Azar ST. Thyroid disorders and diabetes mellitus. J Thyroid Res. 2011; 2011: 439463.
Solá E, Morillas C, Garzón S, Gómez-Balaguer M, Hernández-Mijares A. Association between diabetic ketoacidosis and thyrotoxicosis. Acta Diabetol. 2002; 39(4): 235-237.
Mullur R, Liu YY, Brent GA. Thyroid hormone regulation of metabolism. Physiol Rev. 2014; 94(2): 355-382.
Karbalaei N, Noorafshan A, Hoshmandi E. Impaired glucose-stimulated insulin secretion and reduced beta-cell mass in pancreatic islets of hyperthyroid rats. Exp Physiol. 2016; 101(8): 1114-1127.
Long L, Qiu H, Cai B, Chen N, Lu X, Zheng S, et al. Hyperglycemia induced testicular damage in type 2 diabetes mellitus rats exhibiting microcirculation impairments associated with vascular endothelial growth factor decreased via PI3K/Akt pathway. Oncotarget. 2018; 9(4): 5321-5336.
Governa P, Baini G, Borgonetti V, Cettolin G, Giachetti D, Magnano AR, et al. Phytotherapy in the management of diabetes: A Review. Molecules. 2018; 23(1): 105.
Salehi B, Ata A, V Anil Kumar N, Sharopov F, Ramírez-Alarcón K, Ruiz-Ortega A, et al. Antidiabetic potential of medicinal plants and their active components. Biomolecules. 2019; 9(10): 551.
Jung M, Park M, Lee HC, Kang YH, Kang ES, Kim SK. Antidiabetic agents from medicinal plants. Curr Med Chem. 2006; 13(10): 1203-1218.
Choudhury H, Pandey M, Hua CK, Mun CS, Jing JK, Kong L, et al. An update on natural compounds in the remedy of diabetes mellitus: A systematic review. J Tradit Complement Med. 2018; 8(3): 361-376.
Xu X, Shan B, Liao CH, Xie JH, Wen PW, Shi JY. Anti-diabetic properties of Momordica charantia L. polysaccharide in alloxan-induced diabetic mice. Int J Biol Macromol. 2015; 81: 538-543.
Rina R, Rafiquzzaman M, Hasmah A. Spectrophotometer determination of total phenol and flavanoid content in manjakani (Quercus infectoria) extracts. Heal Env J. 2011; 2(1): 9-13.
Aba PE, Asuzu IU. Mechanisms of actions of some bioactive anti-diabetic principles from phytochemicals of medicinal plants: A review Indian J Nat Prod Resour. 2018; 9(2): 85-96.
Aguayo-Mazzucato C, Zavacki AM, Marinelarena A, Hollister-Lock J, El Khattabi I, Marsili A, et al. Thyroid hormone promotes postnatal rat pancreatic β-cell development and glucose-responsive insulin secretion through MAFA. Diabetes. 2013; 62(5): 1569-1580.
Holsberger DR, Cooke PS. Understanding the role of thyroid hormone in Sertoli cell development: a mechanistic hypothesis. Cell Tissue Res. 2005; 322(1): 133-140.
Mendis-Handagama SM, Siril Ariyaratne HB. Leydig cells, thyroid hormones and steroidogenesis. Indian J Exp Biol. 2005; 43(11): 939-962.
Korejo NA, Wei Q, Zheng K, Mao D, Korejo RA, Shah AH, et al. Contemporaneous effects of diabetes mellitus and hypothyroidism on spermatogenesis and immunolocalization of Claudin-11 inside the seminiferous tubules of mice. BMC Dev Bio. 2018; 18: 15.
Nna VU, Bakar ABA, Ahmad A, Mohamed M. Down-regulation of steroidogenesis-related genes and its accompanying fertility decline in streptozotocin-induced diabetic male rats: ameliorative effect of metformin. Andrology. 2019; 7(1): 110-123.
Shoorei H, Khaki A, Khaki AA, Hemmati AA, Moghimian M, Shokoohi M. The ameliorative effect of carvacrol on oxidative stress and germ cell apoptosis in testicular tissue of adult diabetic rats. Biomed Pharmacoth. 2019; 111: 568-578.
AL-Jaff SH, AL-Bayati MA, Abood NA. Anemia and low testosterone associated with male type 2 diabetic patients. Iraqi J. Vet. Med. 2010; 34(2): 58-68.
Ahada A, Mujeebb M, Ahsanc Ha, Siddiqu WA. Nephroprotective potential of Quercus infectoria galls against experimentally induced diabetic nephropathy in rats through inhibition of renal oxidative stress and TGF-β. Animal Cells and Systems. 2016; 20(4): 193-202.
Thakur R, Jain N, Pathak R, Sandhu SS. Practices in wound healing studies of plants. Evid Based Complement Alternat Med. 2011; 2011: 438056.
Lenzen S. The mechanisms of alloxan- and streptozotocin-induced diabetes. Diabetologia. 2008; 51(2): 216-226.
Ostovar M, Akbari A, Anbardar MH, Iraji A, Salmanpour M, Hafez Ghoran S, et al. Effects of Citrullus colocynthis L. in a rat model of diabetic neuropathy. J Integr Med. 2020; 18(1): 59-67.
Mebis L, van den Berghe G. The hypothalamus-pituitary-thyroid axis in critical illness. Neth J Med. 2009; 67(10): 332-340.
Kooti W, Farokhipour M, Asadzadeh Z, Ashtary-Larky D, Asadi-Samani M. The role of medicinal plants in the treatment of diabetes: a systematic review. Electro Physician. 2016; 8(1):1832-1842.
Ige AO, Chidi RN, Egbeluya EE, Jubreel RO, Adele BO, Adewoye EO. Amelioration of thyroid dysfunction by magnesium in experimental diabetes may also prevent diabetes-induced renal impairment. Heliyon. 2019; 5(5): e01660.
Nascimento-Saba CC, Breitenbach MM, Rosenthal D. Pituitary-thyroid axis in short- and long-term experimental diabetes mellitus. Braz J Med Biol Res.1997; 30(2): 269-274.
Mirboluk AA, Rohani F, Asadi R, Eslamian MR. Thyroid function test in diabetic ketoacidosis. Diabetes Metab Syndr. 2017; 11 Suppl 2: S623-S625.
Zhang Z, Liao L, Moore J, Wu T, Wang Z. Antioxidant phenolic compounds from walnut kernels (Juglans regia L.). Food Chemistry 2009; 113(1): 160-165.
Volpe CMO, Villar-Delfino PH, Dos Anjos PMF, Nogueira-Machado JA. Cellular death, reactive oxygen species (ROS) and diabetic complications. Cell Death Dis. 2018; 9(2): 119.
Kaur G, Athar M, Alam MS. Quercus infectoria galls possess antioxidant activity and abrogates oxidative stress-induced functional alterations in murine macrophages. Chem Biol Interact. 2008; 171(3): 272-282.
Li B, Li Y, Liu K, Wang X, Qi J, Wang B, et al. High glucose decreases claudins-5 and -11 in cardiac microvascular endothelial cells: Antagonistic effects of tongxinluo. Endocrine Research. 2017; 42(1): 15-21.
Haverfield JT, Meachem SJ, Nicholls PK, Rainczuk KE, Simpson ER, Stanton PG. Differential permeability of the blood-testis barrier
during reinitiation of spermatogenesis in adult male rats. Endocrinology. 2014; 155(3): 1131-1144.
Ramos-Vara JA, Miller MA, Johnson GC, Pace LW. Immunohistochemical detection of thyroid transcription factor-1, thyroglobulin, and calcitonin in canine normal, hyperplastic, and neoplastic thyroid gland. Vet Pathol. 2002; 39(4): 480-487.
Yamada H, Takano T, Matsuzuka F, Watanabe M, Miyauchi A, Iwatani Y. Transcriptional activity of the 5'-flanking region of the thyroid transcription factor-1 gene in human thyroid cell lines. Genet Mol Biol. 2011; 34(1): 6-10.
Dupain C, Ali HM, Mouhoub TA, Urbinati G, Massaad-Massade L. Induction of TTF-1 or PAX-8 expression on proliferation and tumorigenicity in thyroid carcinomas. Int J Oncol. 2016; 49(3): 1248-1258.
Nagy T, Fisi V, Frank D, Kátai E, Nagy Z, Miseta A. Hyperglycemia-induced aberrant cell proliferation; a metabolic challenge mediated by protein O-GlcNAc modification. Cells. 2019; 8(9): 999.
Lopez R, Arumugam A, Joseph R, Monga K, Boopalan T, Agullo P, et al. Hyperglycemia enhances the proliferation of non-tumorigenic and malignant mammary epithelial cells through increased leptin/IGF1R signaling and activation of AKT/mTOR. PLoS One. 2013; 8(11): e79708.
Yusof W, Abdullah H. Phytochemicals and cytotoxicity of Quercus infectoria ethyl acetate extracts on human cancer cells. Trop Life Sci Res. 2020; 31(1): 69-84.
Zhang HW, Hu JJ, Fu RQ, Liu X, Zhang YH, Li J, et al. Flavonoids inhibit cell proliferation and induce apoptosis and autophagy through downregulation of PI3Kγ mediated PI3K/AKT/mTOR/p70S6K/ULK signaling pathway in human breast cancer cells. Sci Rep. 2018; 8(1): 11255.