Abstract
Untreated hyperthyroidism may develop serious complications. This attempt was made to investigate the potential of Aloe vera gel in regulating experimentally induced hyperthyroidism in rats. Female Wistar rats were made hyperthyroid with L-thyroxine (L-T4) at 0.5 mg/kg/day, i.p. for 14 days and the effects of Aloe vera methanolic fraction (AVMF) (50 or 500 mg/kg/day, p.o.,) and a conventional antithyroid drug propylthiouracil (PTU) (10 mg/kg, i.p.) for 30 days were studied in those hyperthyroid rats. At the end, alterations in serum thyroid hormones and thyroid stimulating hormone (TSH); hepatic 5′mono-deiodinase-1(5′D1) activity, oxidative stress markers and antioxidants; serum inflammatory cytokines and the expression of thyrotropin receptor in thyroid gland were evaluated in all experimental animals. Hyperthyroid condition was confirmed by an increase in thyroid hormone levels and hepatic 5′D-1 activity with a decrease in TSH. However, either AVMF or PTU treatment in hyperthyroid rats decreased the levels of thyroid hormones and 5′D1 activity. AVMF administration in T4-induced rats also decreased the oxidative stress markers such as thiobarbituric acid reactive substances and lipid hydroperoxides and increased the antioxidant levels in liver tissues. Levels of liver marker enzymes, cytokines and different lipids were decreased in T4-induced AVMF treated rats. Further, a down regulation in the TSHR expression in thyroid was observed in AVMF or PTU treated groups. All these thyroid inhibiting effects were supported by an improvement in thyroid histology in hyperthyroid rats. It appears, about 15 compounds, as evidenced by LC–MS/MS study, mostly phenolics are involved in this anti-thyroid effects of the test compound.
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References
Ganong WF (1995) The thyroid gland. Review of medical physiology. Appleton & Lange, East Norwalk, pp 290–305
Motomura K, Brent GA (1998) Mechanisms of thyroid hormone action. Implications for the clinical manifestation of thyrotoxicosis. Endocrinol Metab Clin N Am 27:1–23
Papachristos DA, Huynh J, Grossman M, MacIsaac RJ (2015) Liver dysfunction and anti-thyroid therapy. SAGE Open Med Case Rep. https://doi.org/10.1177/2050313X14568335
Daniel A, Tesfa K, Biadgo B (2019) Thyroid dysfunction and cytological patterns among patients requested for thyroid function test in an endemic goiter area of Gondar. Endocrinol, North West Ethiopia Intern J. https://doi.org/10.1155/2019/9106767
Radha MH, Laxmipriya NP (2015) Evaluation of biological properties and clinical effectiveness of Aloe vera: a systematic review. J Tradit Complement Med 5:21–26. https://doi.org/10.1016/j.jtcme.2014.1
Shakib Z, Shahraki N, Razavi BM, Hosseinzadeh H (2019) Aloe vera as an herbal medicine in the treatment of metabolic syndrome: A review. Phytother Res 33:2649–2660. https://doi.org/10.1002/ptr.6465
Lans CA (2006) Ethnomedicines used in Trinidad and Tobago for urinary problems and diabetes mellitus. J Ethnobiol Ethnomed 2:45. https://doi.org/10.1186/1746-4269-2-45
Shao A, Broadmeadow A, Goddard G, Bejar E, Frankos V (2013) Safety of purified decolorized (low anthraquinone) whole leaf Aloe vera (L) Burm f juice in a 3-month drinking water toxicity study in F344 rats. Food Chem Toxicol 57:21–31
Hęś M, Dziedzic K, Górecka D, Jędrusek-Golińska A, Gujska E (2019) Aloe vera (L.) natural sources of antioxidants—a review. Plant Foods Hum Nutr 74:255–265. https://doi.org/10.1007/s11130-019-00747-5
Mancini A, Di Segni C, Raimondo S, Olivieri G, Silvestrini A, Meucci E, Currò D (2016) Thyroid hormones, oxidative stress, and inflammation. Mediators Inflamm 2016:6757154. https://doi.org/10.1155/2016/6757154
Ahmadi R, Abbasi Z, Asgary V (2015) The effects of acute and chronic immobilization stress and aloe vera extract on serum levels of TSH, T3 and T4 in male rats. Zah J Res Med Sci 17(03):e1133
Kar A, Panda S, Bharti S (2002) Relative efficacy of three medicinal plant extracts in the alteration of thyroid hormone concentrations in male mice. J Ethnopharmacol 81(2):281–285
Nahar T, Uddin B, Hossain S, Sikder AM, Ahmed S (2013) Aloe vera gel protects liver from oxidative stress-induced damage in experimental rat model. J Complement Integr Med. https://doi.org/10.1515/jcim-2012-0020
Pandey R, Mahar R, Hasanain M, Shukla SK, Sarkar J, Rameshkumar KB, Kumar B (2016) Rapid screening and quantitative determination of bioactive compounds from fruit extracts of Myristica species and their in vitro antiproliferative activity. Food Chem 211:483–493
Panda S, Sikdar M, Biswas S, Sharma R, Kar A (2019) Allylpyrocatechol, isolated from betel leaf ameliorates thyrotoxicosis in rats by altering thyroid peroxidase and thyrotropin receptors. Sci Rep 229(1):12276. https://doi.org/10.1038/s41598-019-48653-9
Beya W, Davidson B, Erlwanger KH (2012) The effects of crude aqueous and alcohol extracts of Aloe vera on growth and abdominal viscera of suckling rats. Afr J Tradit Complement Altern Med 9(4):553–560
Panda S, Sharma R, Kar A (2019) Chavibetol corrects thyrotoxicosis through alterations in thyroid peroxidase. Naunyn Schmiedebergs Arch Pharmacol 392(5):541–550
Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxidation in animal tissues by thiobarbituric acid reaction. Annals of Biochem 95:351–358
Jiang ZY, Hunt JV, Wolff SP (1992) Ferrous ion oxidation in the presence of xylenol orange for detection of lipid hydroperoxide in low density lipoprotein. Anal Biochem 202:384–389
Marklund S, Marklund G (1974) Involvement of superoxide anion radical in the oxidation of pyrogallol: a convenient assay for superoxide dismutase. Eur J Biochem 47:469–474
Aebi H (1983) Catalase. In: Bergmeyer HU (ed) Methods in enzymology, 2nd edn. Academic Press, New York, pp 276–286
Rotruck JT et al (1973) Selenium: biochemical role as a component of glutathione peroxidase. Science 179:588–590
Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 33:574–576
Ködding R, Fuhrmann H, von zur Mühlen A (1986) Investigations on iodothyronine deiodinase activity in the maturing rat brain. Endocrinol 118:1347–1352
Baginske ES, Fod PP, Zak B (1974) In: Bregmeyer H (ed) Methods in enzymatic analysis. Academic Press, New York, pp 876–880
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with Folin-phenol reagent. J Biol Chem 193:265–275
Pietrzak W, Nowak R, Gawlik-Dziki U, Lemieszek MK, Rzeski W (2017) LC-ESI-MS/MS identification of biologically active phenolic compounds in mistletoe berry extracts from different host trees. Molecules. https://doi.org/10.3390/molecules22040624
Riis AL, Gravholt CH, Djurhuus CB, Nørrelund H, Jørgensen JO, Weeke J, Møller NJ (2002) Elevated regional lipolysis in hyperthyroidism. Clin Endocrinol Metab 87:4747–4753
Panda S, Kar A (2011) Periplogenin, isolated from Lagenaria siceraria, ameliorates L-T4-induced hyperthyroidism and associated cardiovascular problems. Horm Metab Res 43(3):188–193
Da-Silva MM, Gonçalves CFL, Miranda-Alves L, Fortunato RS, Carvalho DP, Ferreira ACF (2019) Inhibition of Type 1 iodothyronine deiodinase by bisphenol A. Horm Metab Res 51:671–677
Brent GA (2008) Clinical practice. Graves' disease. New Engl J Med 358:2594–2605
Liberopoulos EN, Elisaf MS (2002) Dyslipidemia in patients with thyroid disorders. Hormones (Athens) 1:218–223
Liju VB, Jeena K, Kuttan R (2013) Acute and subchronic toxicity as well as mutagenic evaluation of essential oil from turmeric (Curcuma longa l). Food Chem Toxicol 53:52–61
Mishra P, Paital B, Jena S, Swain SS, Kumar S, Yadav MK, Chainy GBN, Samanta L (2019) Possible activation of NRF2 by Vitamin E/Curcumin against altered thyroid hormone induced oxidative stress via NFĸB/AKT/mTOR/KEAP1 signalling in rat heart. Sci Rep 15:7408. https://doi.org/10.1038/s41598-019-43320-5
Zhao P, Hu Z, Ma W, Zang L, Tian Z, Hou Q (2020) Quercetin alleviates hyperthyroidism-induced liver damage via Nrf2 Signaling pathway. BioFactors. https://doi.org/10.1002/biof.1626
Gomaa AM, Abd El-Aziz EA (2016) Omega-3 fatty acids decreases oxidative stress, tumor necrosis factor-alpha, and interleukin-1 beta in hyperthyroidism-induced hepatic dysfunction rat model. Pathophysiology 23(4):295–301
Akamizu T, Ikuyama S, Saji M, Kosugi S, Kozak C, McBride OW, Kohn LD (1990) Cloning, chromosomal assignment, and regulation of the rat thyrotropin receptor: expression of the gene is regulated by thyrotropin, agents that increase cAMP levels, and thyroid autoantibodies. Proc Natl Acad Sci U S A 87:5677–5681
Takamatsu J, Takeda K, Katayama S, Sakane S, Morita S, Kuma K, Ohsawa N (1992) Epithelial hyperplasia and decreased colloid content of the thyroid gland in triiodothyronine-predominant Graves’ disease. J Clin Endocrinol Metab 75(4):1145–1150
Mohamadin AM, Hammad LN, El-Bab MF, Abdel Gawad HS (2007) Attenuation of oxidative stress in plasma and tissues of rats with experimentally induced hyperthyroidism by caffeic acid phenylethyl ester. Basic and Clinical Pharmacol and Toxicol 100:84–90
van der Heide D, Kastelijn J, Schröder-van der Elst JP (2003) Flavonoids and thyroid disease. BioFactors 19(3–4):113–119
Chandra AK, De N (2013) Catechin induced modulation in the activities of thyroid hormone synthesizing enzymes leading to hypothyroidism. Mol Cell Biochem 374:37–48
Pistollato F, Masias M, Agudo P, Giampieri F, Battino M (2019) Effects of phytochemicals on thyroid function and their possible role in thyroid disease. Ann N Y Acad Sci 1443:3–19. https://doi.org/10.1111/nyas.13980
Acknowledgements
This investigation was supported by the grant received from Department of Science and Technology (DST), New Delhi, India,under Women Scientist scheme to Dr. S. Panda [REF: SR/WOS-A/LS-407].LC–ESI–MS study was made using the SAIF facilities from CDRI, Lucknow, India.
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Panda, S., Sharma, R., Khan, A. et al. Ameliorative effect of Aloe gel against L-T4-induced hyperthyroidism via suppression of thyrotropin receptors, inflammation and oxidative stress. Mol Biol Rep 47, 2801–2810 (2020). https://doi.org/10.1007/s11033-020-05405-7
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DOI: https://doi.org/10.1007/s11033-020-05405-7