Abstract
This study was conducted to elucidate the ameliorative potential of lycopene (LYC) against the metabolic toxicity induced by bisphenol A (BPA) in rats. Male rats (n = 28) were divided into 4 equal groups: control group, LYC group was given lycopene (10 mg/kg BW), BPA group was given 10 mg/kg BW of BPA, and the last group was administered BPA and LYC at 10 mg/kg via gavage for 90 consecutive days. Body weight (BW) gain, lipid profile, and total antioxidant capacity (TAC) were assessed. Oral glucose tolerance test (OGTT), homeostasis model assessment–estimated insulin resistance (HOMA-IR), thyroid hormones, interleukin-1 beta (IL-1β), leptin, and resistin were assayed. Moreover, immunohistochemistry of TNF-α was performed in adipose tissue. BPA-treated rats showed significant reduction in BW gain and deteriorations in lipid profile, TAC, OGTT, and thyroid hormones as well as significant increases in HOMA-IR, IL-1β, leptin, and resistin. While, improvement of metabolic parameters was observed when LYC was administrated with BPA. Intense TNF-α immunostaining was detected in the fat of BPA-treated rats but the intensity decreased when LYC was administrated with BPA. In conclusion, LYC ameliorated the adverse effects of BPA on metabolism through its antioxidant potential and its reduction of TNF-α expression in adipose tissue.
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Abdel-Daim M, Eltaysh R, Hassan A, Mousa S (2018) Lycopene attenuates tulathromycin and diclofenac sodium-induced cardiotoxicity in mice. Int J Mol Sci 19(2):344–359. https://doi.org/10.3390/ijms19020344
Abdel-Rahman HG, Abdelrazek H, Zeidan DW, Mohamed RM, Abdelazim AM (2018) Lycopene: hepatoprotective and antioxidant effects toward bisphenol A-induced toxicity in female Wistar rats. Oxidative Med Cell Longev 2018:1–8. https://doi.org/10.1155/2018/5167524
Abdul-Hamid M, Salah M (2013) Lycopene reduces deltamethrin effects induced thyroid toxicity and DNA damage in albino rats. JOBAZ 66(4):155–163. https://doi.org/10.1016/j.jobaz.2013.08.001
Agarwal A, Allamaneni SS (2004) Role of free radicals in female reproductive diseases and assisted reproduction. Reprod BioMed Online 9(3):338–347. https://doi.org/10.1016/S1472-6483(10)62151-7
Ahangarpour A, Afshari G, Mard SA, Khodadadi A, Hashemitabar M (2016) Alteration effect of Exendin-4 on oxidative stress and metabolic disorders induced by Bisphenol A in adult male mice. Jentashapir J Health Res 7(5):1–6. https://doi.org/10.17795/jjhr-37836
Allain CC, Poon LS, Chan CS, Richmond W, Fu PC (1974) Enzymatic determination of total serum cholesterol. Clin Chem 20(4):470–475
Alonso-Magdalena P, Vieira E, Soriano S, Menes L, Burks D, Quesada I, Nadal A (2010) Bisphenol A exposure during pregnancy disrupts glucose homeostasis in mothers and adult male offspring. Environ Health Perspect 118(9):1243–1250. https://doi.org/10.1289/ehp.1001993
Angle BM, Do RP, Ponzi D, Stahlhut RW, Drury BE, Nagel SC, Welshons WV, Besch-Williford CL, Palanza P, Parmigiani S (2013) Metabolic disruption in male mice due to fetal exposure to low but not high doses of bisphenol A (BPA): evidence for effects on body weight, food intake, adipocytes, leptin, adiponectin, insulin and glucose regulation. Reprod Toxicol 42:256–268. https://doi.org/10.1016/j.reprotox.2013.07.017
Ariemma F, D’Esposito V, Liguoro D, Cabaro S, Liotti A, Cimmino I, Longo M, Beguinot F, Formisano P, Valentino R (2016) Low-dose bisphenol-A impairs adipogenesis and generates dysfunctional 3T3-L1 adipocytes. PLoS One 11(3):1–16. https://doi.org/10.1371/journal.pone.0150762
Askari H, Tykodi G, Liu J, Dagogo-Jack S (2010) Fasting plasma leptin level is a surrogate measure of insulin sensitivity. J Clin Endocrinol Metab 95(8):3836–3843. https://doi.org/10.1210/jc.2010-0296
Bachorik PS (2000) Measurement of low-density-lipoprotein cholesterol handbook of lipoprotein testing, pp. 245-64
Bancroft JD, Cook HC (1994) Manual of histological techniques and their diagnostic application. Churchill Livingstone, Edinburgh, New York
Blanca AJ, Ruiz-Armenta MV, Zambrano S, Salsoso R, Miguel-Carrasco JL, Fortuño A, Revilla E, Mate A, Vázquez CM (2016) Leptin induces oxidative stress through activation of nadph oxidase in renal tubular cells: antioxidant effect of L-carnitine. J Cell Biochem 117(10):2281–2288. https://doi.org/10.1002/jcb.25526
Boström EA, Tarkowski A, Bokarewa M (2009) Resistin is stored in neutrophil granules being released upon challenge with inflammatory stimuli. Biochim Biophys Acta 1793(12):1894–1900. https://doi.org/10.1016/j.bbamcr.2009.09.008
Cai D, Yuan M, Frantz DF, Melendez PA, Hansen L, Lee J, Shoelson SE (2005) Local and systemic insulin resistance resulting from hepatic activation of IKK-β and NF-κB. Nat Med 11(2):183–190. https://doi.org/10.1038/nm1166
Chang C, Dong R, Miyazaki A, Sakashita N, Zhang Y, Liu J, Guo M, Li B-L, Chang T-Y (2006) Human acyl-CoA: cholesterol acyltransferase (ACAT) and its potential as a target for pharmaceutical intervention against atherosclerosis. Acta Biochim Biophys Sin 38(3):151–156. https://doi.org/10.1111/j.1745-7270.2006.00154.x
Chen G, Ni Y, Nagata N, Zhuge F, Xu L, Nagashimada M, Yamamoto S, Ushida Y, Fuke N, Suganuma H (2019) Lycopene alleviates obesity-induced inflammation and insulin resistance by regulating M1/M2 status of macrophages. Mol Nutr Food Res: 1900602. https://doi.org/10.1002/mnfr.201900602
Couleau N, Falla J, Beillerot A, Battaglia E, D’Innocenzo M, Plancon S, Laval-Gilly P, Bennasroune A (2015) Effects of endocrine disruptor compounds, alone or in combination, on human macrophage-like THP-1 cell response. PLoS One 10(7):e0131428. https://doi.org/10.1371/journal.pone.0131428
Czeczuga B, Czeczuga-Semeniuk E, Semeniuk A (2005) Carotenoids and carotenoproteins in Asellus aquaticus L.(Crustacea: Isopoda). Folia Biol 53(3–4):109–114. https://doi.org/10.3409/173491605775142756
Desai M, Ferrini M, Jellyman J, Han G, Ross M (2018) In vivo and in vitro bisphenol A exposure effects on adiposity. J Dev Orig Hlth Dis 9(6):678–687. https://doi.org/10.1017/S2040174418000600
Duntas LH (2002) Thyroid disease and lipids. Thyroid 12(4):287–293. https://doi.org/10.1089/10507250252949405
Esser N, Legrand-Poels S, Piette J, Scheen AJ, Paquot N (2014) Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes. Diabetes Res Clin Pract 105(2):141–150. https://doi.org/10.1016/j.diabres.2014.04.006
Esteghamati A, Khalilzadeh O, Anvari M, Rashidi A, Mokhtari M, Nakhjavani M (2009) Association of serum leptin levels with homeostasis model assessment–estimated insulin resistance and metabolic syndrome: the key role of central obesity. Metab Syndr Relat Disord 7(5):447–452. https://doi.org/10.1089/met.2008.0100
Fantuzzi G, Faggioni R (2000) Leptin in the regulation of immunity, inflammation, and hematopoiesis. J Leukoc Biol 68(4):437–446. https://doi.org/10.1189/jlb.68.4.437
Finkelstein EA, Trogdon JG, Cohen JW, Dietz W (2009) Annual medical spending attributable to obesity: payer-and service-specific estimates. Health affairs (Project Hope) 28(5):822–831. https://doi.org/10.1377/hlthaff.28.5.w822
Fossati P, Prencipe L (1982) Serum triglycerides determined colorimetrically with an enzyme that produces hydrogen peroxide. Clin Chem 28(10):2077–2080
García-Arevalo M, Alonso-Magdalena P, Dos Santos JR, Quesada I, Carneiro EM, Nadal A (2014) Exposure to bisphenol-A during pregnancy partially mimics the effects of a high-fat diet altering glucose homeostasis and gene expression in adult male mice. PLoS One 9(6):1–13. https://doi.org/10.1371/journal.pone.0100214
Geng S, Wang S, Zhu W, Xie C, Li X, Wu J, Zhu J, Jiang Y, Yang X, Li Y, Chen Y, Wang X, Meng Y, Zhu M, Wu R, Huang C, Zhong C (2017) Curcumin attenuates BPA-induced insulin resistance in HepG2 cells through suppression of JNK/p38 pathways. Toxicol Lett 272:75–83. https://doi.org/10.1016/j.toxlet.2017.03.011
Hassan ZK, Elobeid MA, Virk P, Omer SA, ElAmin M, Daghestani MH, AlOlayan EM (2012) Bisphenol A induces hepatotoxicity through oxidative stress in rat model. Oxidative Med Cell Longev 2012:1–6. https://doi.org/10.1155/2012/194829
Hotamisligil GS, Murray DL, Choy LN, Spiegelman BM (1994) Tumor necrosis factor alpha inhibits signaling from the insulin receptor. Proc Natl Acad Sci 91(11):4854–4858. https://doi.org/10.1073/pnas.91.11.4854
Huang GM, Tian XF, Fang XD, Ji FJ (2016) Waterborne exposure to bisphenol F causes thyroid endocrine disruption in zebrafish larvae. Chemosphere 147:188–194. https://doi.org/10.1016/j.chemosphere.2015.12.080
Hurrle S, Hsu WH (2017) The etiology of oxidative stress in insulin resistance. Biom J 40(5):257–262. https://doi.org/10.1016/j.bj.2017.06.007
Icel E, Icel A, Uçak T, Karakurt Y, Elpeze B, Keskin Çimen F, Süleyman H (2019) The effects of lycopene on alloxan induced diabetic optic neuropathy. Cutan Ocul Toxicol 38(1):88–92. https://doi.org/10.1080/15569527.2018.1530258
Jiang W, Guo M-H, Hai X (2016) Hepatoprotective and antioxidant effects of lycopene on non-alcoholic fatty liver disease in rat. World J Gastroenterol 22(46):10180–10188. https://doi.org/10.3748/wjg.v22.i46.10180
Kang YE, Kim JM, Joung KH, Lee JH, You BR, Choi MJ, Ryu MJ, Ko YB, Lee MA, Lee J, Ku BJ, Shong M, Lee KH, Kim HJ (2016) The roles of adipokines, proinflammatory cytokines, and adipose tissue macrophages in obesity-associated insulin resistance in modest obesity and early metabolic dysfunction. PLoS One 11(4):1–14. https://doi.org/10.1371/journal.pone.0154003
Khalil SR, Awad A, Mohammed HH (2017a) Behavioral response and gene expression changes in fipronil-administered male Japanese quail (Coturnix japonica). Environ Pollut 223:51–61. https://doi.org/10.1016/j.envpol.2016.12.027
Khalil SR, Awad A, Mohammed HH, Nassan MA (2017b) Imidacloprid insecticide exposure induces stress and disrupts glucose homeostasis in male rats. Environ Toxicol Pharmacol 55:165–174. https://doi.org/10.1016/j.etap.2017.08.017
Kim H-J, Higashimori T, Park S-Y, Choi H, Dong J, Kim Y-J, Noh H-L, Cho Y-R, Cline G, Kim Y-B (2004) Differential effects of interleukin-6 and -10 on skeletal muscle and liver insulin action in vivo. Diabetes 53(4):1060–1067. https://doi.org/10.2337/diabetes.53.4.1060
Kirkley AG, Sargis RM (2014) Environmental endocrine disruption of energy metabolism and cardiovascular risk. Curr Diab Rep 14(6):494–494. https://doi.org/10.1007/s11892-014-0494-0
Kong K-W, Rajab NF, Prasad KN, Ismail A, Markom M, Tan C-P (2010) Lycopene-rich fractions derived from pink guava by-product and their potential activity towards hydrogen peroxide-induced cellular and DNA damage. Food Chem 123(4):1142–1148. https://doi.org/10.1016/j.foodchem.2010.05.077
Kuo C-C, Moon K, Thayer KA, Navas-Acien A (2013) Environmental chemicals and type 2 diabetes: an updated systematic review of the epidemiologic evidence. Curr Diab Rep 13(6):831–849. https://doi.org/10.1007/s11892-013-0432-6
Lang IA, Galloway TS, Scarlett A, Henley WE, Depledge M, Wallace RB, Melzer D (2008) Association of urinary bisphenol A concentration with medical disorders and laboratory abnormalities in adults. JAMA 300(11):1303–1310. https://doi.org/10.1001/jama.300.11.1303
Lapid K, Graff JM (2017) Form(ul)ation of adipocytes by lipids. Adipocyte 6(3):176–186. https://doi.org/10.1080/21623945.2017.1299298
Le Magueresse-Battistoni B, Labaronne E, Vidal H, Naville D (2017) Endocrine disrupting chemicals in mixture and obesity, diabetes and related metabolic disorders. World J Biol Chem 8(2):108–119. https://doi.org/10.4331/wjbc.v8.i2.108
Lee D-H, Steffes MW, Sjödin A, Jones RS, Needham LL, Jacobs DR Jr (2010) Low dose of some persistent organic pollutants predicts type 2 diabetes: a nested case–control study. Environ Health Perspect 118(9):1235–1242. https://doi.org/10.1289/ehp.0901480
Lee M-J, Wu Y, Fried SK (2013) Adipose tissue heterogeneity: implication of depot differences in adipose tissue for obesity complications. Mol Asp Med 34(1):1–11. https://doi.org/10.1016/j.mam.2012.10.001
Li J, Huang M, Shen X (2014) The association of oxidative stress and pro-inflammatory cytokines in diabetic patients with hyperglycemic crisis. J Diabetes Complicat 28(5):662–666. https://doi.org/10.1016/j.jdiacomp.2014.06.008
Liang G, Ning WH, Ling Z, Yuan PF, Yue J, Wei W, Hong JL (2016) Effect of perinatal bisphenol A exposure on serum lipids and lipid enzymes in offspring rats of different sex. Biomed Environ Sci 29(9):686–689. https://doi.org/10.3967/bes2016.092
Liu J, Yu P, Qian W, Li Y, Zhao J, Huan F, Wang J, Xiao H (2013) Perinatal bisphenol A exposure and adult glucose homeostasis: identifying critical windows of exposure. PLoS One 8(5):1–12. https://doi.org/10.1371/journal.pone.0064143
Luvizotto RAM, Nascimento AF, Imaizumi E, Pierine DT, Conde SJ, Correa CR, Yeum K-J, Ferreira ALA (2013) Lycopene supplementation modulates plasma concentrations and epididymal adipose tissue mRNA of leptin, resistin and IL-6 in diet-induced obese rats. Br J Nutr 110(10):1803–1809. https://doi.org/10.1017/S0007114513001256
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419
Mancuso P (2016) The role of adipokines in chronic inflammation. Immunotargets Ther 5:47–56. https://doi.org/10.2147/ITT.S73223
Michałowicz J (2014) Bisphenol A–sources, toxicity and biotransformation. Environ Toxicol Pharmacol 37(2):738–758. https://doi.org/10.1016/j.etap.2014.02.003
Mohammed ET, Hashem KS, Ahmed AE, Aly MT, Aleya L, Abdel-Daim MM (2019) Ginger extract ameliorates bisphenol A (BPA)-induced disruption in thyroid hormones synthesis and metabolism: involvement of Nrf-2/HO-1 pathway. Sci Total environ: 134664. https://doi.org/10.1016/j.scitotenv.2019.134664
Moriyama K, Tagami T, Akamizu T, Usui T, Saijo M, Kanamoto N, Hataya Y, Shimatsu A, Kuzuya H, Nakao K (2002) Thyroid hormone action is disrupted by bisphenol a as an antagonist. J Clin Endocrinol Metab 87(11):5185–5190. https://doi.org/10.1210/jc.2002-020209
Moshyedi AK, Josephs MD, Abdalla EK, MacKay SL, Edwards CK, Copeland EM, Moldawer LL (1998) Increased leptin expression in mice with bacterial peritonitis is partially regulated by tumor necrosis factor alpha. Infect Immun 66(4):1800–1802
NRC (1995) Nutrient requirements of laboratory animals. National Academies Press, USA
Parker RS (1996) Absorption, metabolism, and transport of carotenoids. FASEB J 10(5):542–551. https://doi.org/10.1096/fasebj.10.5.8621054
Pederson RA, White HA, Schlenzig D, Pauly RP, McIntosh CH, Demuth H-U (1998) Improved glucose tolerance in Zucker fatty rats by oral administration of the dipeptidyl peptidase IV inhibitor isoleucine thiazolidide. Diabetes 47(8):1253–1258. https://doi.org/10.1006/bbrc.2001.4999
Raghuraman G, Zuniga MC, Yuan H, Zhou W (2016) PKCε mediates resistin-induced NADPH oxidase activation and inflammation leading to smooth muscle cell dysfunction and intimal hyperplasia. Atherosclerosis 253:29–37. https://doi.org/10.1016/j.atherosclerosis.2016.08.015
Rencuzogullari N, Erdogan S (2007) Oral administration of lycopene reverses cadmium-suppressed body weight loss and lipid peroxidation in rats. Biol Trace Elem Res 118(2):175–183. https://doi.org/10.1007/s12011-007-0027-7
Routledge EJ, White R, Parker MG, Sumpter JP (2000) Differential effects of xenoestrogens on coactivator recruitment by estrogen receptor (ER) α and ERβ. J Biol Chem 275(46):35986–35993. https://doi.org/10.1074/jbc.M006777200
Sahin K, Onderci M, Sahin N, Gursu MF, Khachik F, Kucuk O (2006) Effects of lycopene supplementation on antioxidant status, oxidative stress, performance and carcass characteristics in heat-stressed Japanese quail. J Therm Biol 31(4):307–312. https://doi.org/10.1016/j.jtherbio.2005.12.006
Sales LB, Kamstra J, Cenijn P, Van Rijt L, Hamers T, Legler J (2013) Effects of endocrine disrupting chemicals on in vitro global DNA methylation and adipocyte differentiation. Toxicol in Vitro 27(6):1634–1643. https://doi.org/10.1016/j.tiv.2013.04.005
Sarraf P, Frederich RC, Turner EM, Ma G, Jaskowiak NT, Rivet DJ, Flier JS, Lowell BB, Fraker DL, Alexander HR (1997) Multiple cytokines and acute inflammation raise mouse leptin levels: potential role in inflammatory anorexia. J Exp Med 185(1):171–176. https://doi.org/10.1084/jem.185.1.171
Schmutzler C, Bacinski A, Gotthardt I, Huhne K, Ambrugger P, Klammer H, Schlecht C, Hoang-Vu C, Grüters A, Wuttke W (2007) The ultraviolet filter benzophenone 2 interferes with the thyroid hormone axis in rats and is a potent in vitro inhibitor of human recombinant thyroid peroxidase. Endocrinology 148(6):2835–2844. https://doi.org/10.1210/en.2006-1280
Sinha RA, Singh BK, Yen PM (2018) Direct effects of thyroid hormones on hepatic lipid metabolism. Nat Rev Endocrinol 14(5):259–269. https://doi.org/10.1038/nrendo.2018.10
Song S, Zhang L, Zhang H, Wei W, Jia L (2014) Perinatal BPA exposure induces hyperglycemia, oxidative stress and decreased adiponectin production in later life of male rat offspring. Int J Environ Res Public Health 11(4):3728–3742. https://doi.org/10.3390/ijerph110403728
Sun H, Shen O-X, Wang X-R, Zhou L, S-q Z, X-d C (2009) Anti-thyroid hormone activity of bisphenol A, tetrabromobisphenol A and tetrachlorobisphenol A in an improsved reporter gene assay. Toxicol in Vitro 23(5):950–954. https://doi.org/10.1016/j.tiv.2009.05.004
Tang T, Yang Y, Chen Y, Tang W, Wang F, Diao X (2015) Thyroid disruption in zebrafish larvae by short-term exposure to bisphenol AF. Int J Environ Res Public Health 12(10):13069–13084. https://doi.org/10.3390/ijerph121013069
Tawfik SH, Mahmoud BF, Saad MI, Shehata M, Kamel MA, Helmy MH (2015) Similar and additive effects of ovariectomy and diabetes on insulin resistance and lipid metabolism. Biochem Res Int 2015:1–8. https://doi.org/10.1155/2015/567945
Tiwari D, Vanage G (2017) Bisphenol A induces oxidative stress in bone marrow cells, lymphocytes, and reproductive organs of Holtzman rats. Int J Toxicol 36(2):142–152. https://doi.org/10.1177/1091581817691224
Usman A, Ahmad M (2016) From BPA to its analogues: is it a safe journey? Chemosphere 158:131–142. https://doi.org/10.1016/j.chemosphere.2016.05.070
Vandenberg LN, Maffini MV, Sonnenschein C, Rubin BS, Soto AM (2009) Bisphenol-A and the great divide: a review of controversies in the field of endocrine disruption. Endocr Rev 30(1):75–95. https://doi.org/10.1210/er.2008-0021
Verghese M, Richardson J, Boateng J, Shackelford L, Howard C, Walker L, Chawan C (2008) Dietary lycopene has a protective effect on cardiovascular disease in New Zealand male rabbits. J Biol Sci 8(2):268–277. https://doi.org/10.3923/jbs.2008.268.277
Wang T, Li M, Chen B, Xu M, Xu Y, Huang Y, Lu J, Chen Y, Wang W, Li X (2012) Urinary bisphenol A (BPA) concentration associates with obesity and insulin resistance. J Clin Endocrinol Metab 97(2):223–227. https://doi.org/10.1210/jc.2011-1989
Yang J, Eliasson B, Smith U, Cushman SW, Sherman AS (2012) The size of large adipose cells is a predictor of insulin resistance in first-degree relatives of type 2 diabetic patients. Obesity 20(5):932–938. https://doi.org/10.1038/oby.2011.371
Yang M, Chen M, Wang J, Xu M, Sun J, Ding L, Lv X, Ma Q, Bi Y, Liu R (2016) Bisphenol a promotes adiposity and inflammation in a nonmonotonic dose-response way in 5-week-old male and female C57BL/6J mice fed a low-calorie diet. Endocrinology 157(6):2333–2345. https://doi.org/10.1210/en.2015-1926
Zhang R, Su D, Zhu W, Huang Q, Liu M, Xue Y, Zhang Y, li D, Zhao A, Liu Y (2014) Estrogen suppresses adipogenesis by inhibiting S100A16 expression. J Mol Endocrinol 52(3): 235–244. https://doi.org/10.1530/JME-13-0273
Zheng Z, Yin Y, Lu R, Jiang Z (2019) Lycopene ameliorated oxidative stress and inflammation in type 2 diabetic rats. J Food Sci 84(5):1194–1200. https://doi.org/10.1111/1750-3841.14505
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Elgawish, R.A., El-Beltagy, M.A., El-Sayed, R.M. et al. Protective role of lycopene against metabolic disorders induced by chronic bisphenol A exposure in rats. Environ Sci Pollut Res 27, 9192–9201 (2020). https://doi.org/10.1007/s11356-019-07509-5
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DOI: https://doi.org/10.1007/s11356-019-07509-5