Effects of quercetin and vitamin E on ovariectomy-induced oxidative stress in rat serum and tibia
Keywords:menopause, ovariectomy, osteoporosis, oxidative stress, quercetin, vitamin E
- Estrogen deficiency after ovariectomy induces an imbalance between the production of reactive oxygen species and the antioxidant defense system, leading to oxidative stress and resulting complications.
- Administration of either quercetin or vitamin E improved oxidative stress in ovariectomized rats. However, the coadministration of quercetin and vitamin E had a weaker improving effect than when either compound was applied alone.
- Ovariectomy-induced oxidative stress could be ameliorated by administration of either quercetin or vitamin E and could alleviate ovariectomy-induced dysfunction.
Abstract: Estrogen deficiency after menopause accelerates redox imbalance, leading to oxidative stress (OS) and other postmenopausal complications such as osteoporosis and cardiovascular disease. In the present study, the effects of quercetin (Q), vitamin E (vitE) and estradiol (E2) on the oxidative status in ovariectomized (OVX) rats were investigated. OVX animals were treated with Q (15 mg/kg/day), vitE (60 mg/kg/day), E2 (10 µg/kg/day) and Q (7.5 mg/kg/day)+vitE (30 mg/kg/day) for 10 weeks. OS markers were analyzed in the serum and tibia of rats. Data indicated that after ovariectomy, rats exhibited a reduction in serum and tibia antioxidants and elevation of oxidant markers. The activities of antioxidant enzymes (AOEs), glutathione peroxidase (GPx), catalase (CAT) and glutathione reductase were decreased and the glutathione (GSH) content was reduced, whereas the malondialdehyde (MDA) level was increased. Treatment with Q, vitE and E2 markedly reversed these changes and improved OS. In conclusion, prevention by antioxidant agents, including Q and vitE, could be a potential approach in the management of menopause-related complications.
Received: November 15, 2019; Revised: December 15, 2019; Accepted: January 13, 2020; Published online: January 20, 2020
How to cite this article: Vakili S, Zal F, Mostafavipour Z, Savardashtaki A, Jafari Khorchani M, Hassanpour A. Effects of quercetin and vitamin E on ovariectomy-induced oxidative stress in ratserum and tibia. Arch Biol Sci. 2020;72(1):95-104.
El-Fattah AIA, Fathy MM, Ali ZY, El-Garawany AE-RA, Mohamed EK. Enhanced therapeutic benefit of quercetin-loaded phytosome nanoparticles in ovariectomized rats. Chem Biol Interact. 2017;271:30-8.
Gompel A. Menopausal Treatment. In: Huhtaniemi I, Martini L, editors. Encyclopedia of Endocrine Diseases. 2nd ed. Oxford: Academic Press; 2019. p. 634-45.
Muthusami S, Ramachandran I, Muthusamy B, Vasudevan G, Prabhu V, Subramaniam V, Jagadeesan A, Narasimhan S. Ovariectomy induces oxidative stress and impairs bone antioxidant system in adult rats. Clin Chim Acta. 2005;360(1-2):81-6.
Vijayan V, Khandelwal M, Manglani K, Singh RR, Gupta S, Surolia A. Homocysteine alters the osteoprotegerin/RANKL system in the osteoblast to promote bone loss: pivotal role of the redox regulator forkhead O1. Free Radic Biol Med. 2013;61:72-84.
Huang Q, Shi J, Gao B, Zhang H-Y, Fan J, Li X-J, Fan J-Z, Han Y-H, Zhang J-K, Yang L. Gastrodin: an ancient Chinese herbal medicine as a source for anti-osteoporosis agents via reducing reactive oxygen species. Bone. 2015;73:132-44.
Baek KH, Oh KW, Lee WY, Lee SS, Kim MK, Kwon HS, Rhee EJ, Han JH, Song KH, Cha BY. Association of oxidative stress with postmenopausal osteoporosis and the effects of hydrogen peroxide on osteoclast formation in human bone marrow cell cultures. Calcif Tissue Int. 2010;87(3):226-35.
O’Neill S, Eden J. The pathophysiology of menopausal symptoms. Obstet Gynaecol Reprod Med. 2012;22(3):63-9.
Sawada H, Ibi M, Kihara T, Urushitani M, Honda K, Nakanishi M, Akaike A, Shimohama S. Mechanisms of antiapoptotic effects of estrogens in nigral dopaminergic neurons. FASEB J. 2000;14(9):1202-14.
Morrone MDS, Schnorr CE, Behr GA, Gasparotto J, Bortolin RC, Moresco KS, Bittencourt L, Zanotto-Filho A, Gelain DP, Moreira JCF. Oral administration of curcumin relieves behavioral alterations and oxidative stress in the frontal cortex, hippocampus, and striatum of ovariectomized Wistar rats. J Nutr Biochem. 2016;32:181-8.
Potter B, Schrager S, Dalby J, Torell E, Hampton A. Menopause. Prim Care. 2018;45(4):625-41.
Sarri G, Pedder H, Dias S, Guo Y, Lumsden MA. Vasomotor symptoms resulting from natural menopause: a systematic review and network meta‐analysis of treatment effects from the National Institute for Health and Care Excellence guideline on menopause. BJOG. 2017;124(10):1514-23.
Svatikova A, Hayes SN. Menopause and menopausal hormone therapy in women: cardiovascular benefits and risks. Revista Colombiana de Cardiología. 2018;25:30-3.
Chen J, Zhang N, Wang Y, Wang J, Ji S, Dang W, Li S, Feng L. Estrogenic effects of flavonoid components in xiaoyao powder. Genet Mol Res. 2016;15(1):gmr7500.
Borrelli F, Ernst E. Alternative and complementary therapies for the menopause. Maturitas. 2010;66(4):333-43.
Wang W, Sun C, Mao L, Ma P, Liu F, Yang J, Gao Y. The biological activities, chemical stability, metabolism and delivery systems of quercetin: A review. Trends Food Sci Technol. 2016;56:21-38.
Ekinci Akdemir FN, Gülçin İ, Karagöz B, Soslu R. Quercetin protects rat skeletal muscle from ischemia reperfusion injury. J Enzyme Inhib Med Chem. 2016;31(Sup2):162-6.
Li C, Wang T, Zhang C, Xuan J, Su C, Wang Y. Quercetin attenuates cardiomyocyte apoptosis via inhibition of JNK and p38 mitogen-activated protein kinase signaling pathways. Gene. 2016;577(2):275-80.
Yang X, Zhang W, Zhao Z, Li N, Mou Z, Sun D, Cai Y, Wang W, Lin Y. Quercetin loading CdSe/ZnS nanoparticles as efficient antibacterial and anticancer materials. J Inorg Biochem. 2017;167:36-48.
Smith B, Lucas E, Turner R, Evans G, Lerner M, Brackett D, Stoecker B, Arjmandi B. Vitamin E provides protection for bone in mature hindlimb unloaded male rats. Calcif Tissue Int. 2005;76(4):272-9.
Feresin RG, Johnson SA, Elam ML, Kim J-S, Khalil DA, Lucas EA, Smith BJ, Payton ME, Akhter MP, Arjmandi BH. Effects of vitamin E on bone biomechanical and histomorphometric parameters in ovariectomized rats. J Osteoporos. 2013;2013:825985.
Monteiro SC, Matté C, Bavaresco CS, Netto CA, Wyse AT. Vitamins E and C pretreatment prevents ovariectomy-induced memory deficits in water maze. Neurobiol Learn Mem. 2005;84(3):192-9.
Galli F, Azzi A, Birringer M, Cook-Mills JM, Eggersdorfer M, Frank J, Cruciani G, Lorkowski S, Özer NK. Vitamin E: Emerging aspects and new directions. Free Radic Biol Med. 2017;102:16-36.
Guralp O. Effects of vitamin E on bone remodeling in perimenopausal women: mini review. Maturitas. 2014;79(4):476-80.
Feng Z, Zhang J-t. Long-term melatonin or 17β-estradiol supplementation alleviates oxidative stress in ovariectomized adult rats. Free Radic Biol Med. 2005;39(2):195-204.
Muhammad N, Luke DA, Shuid AN, Mohamed N, Soelaiman I-N. Two different isomers of vitamin e prevent bone loss in postmenopausal osteoporosis rat model. Evid Based Complement Alternat Med. 2012;2012:161527.
Yang Y, Zheng X, Li B, Jiang S, Jiang L. Increased activity of osteocyte autophagy in ovariectomized rats and its correlation with oxidative stress status and bone loss. Biochem Biophys Res Commun. 2014;451(1):86-92.
Mostafavi Pour Z, Vessal M, Zal F, Khoshdel Z, Torabinejad S. Protective effects of vitamin E and/or quercetin co-supplementation on the morphology of kidney in cyclosporine A-treated rats. Iranian J Medic Sci. 2009;34(4):271-6.
Sankar P, Zachariah B, Vickneshwaran V, Jacob SE, Sridhar M. Amelioration of oxidative stress and insulin resistance by soy isoflavones (from Glycine max) in ovariectomized Wistar rats fed with high fat diet: the molecular mechanisms. Exp Gerontol. 2015;63:67-75.
Zal F, Mahdian Z, Zare R, Soghra B, Mostafavi-Pour Z. Combination of vitamin E and folic acid ameliorate oxidative stress and apoptosis in diabetic rat uterus. Int J Vitam Nutr Res. 2014;84(1-2):55-64.
Zal F, Taheri R, Khademi F, Keshavarz E, Rajabi S, Mostafavi-Pour Z. The combined effect of furosemide and propranolol on GSH homeostasis in ACHN renal cells. Toxicol Mech Methods. 2014;24(6):412-6.
Yarahmadi A, Zal F, Bolouki A. Protective effects of quercetin on nicotine induced oxidative stress in 'HepG2 cells'. Toxicol Mech Methods. 2017;27(8):609-14.
Mashhoody T, Rastegar K, Zal F. Perindopril may improve the hippocampal reduced glutathione content in rats. Adv Pharm Bull. 2014;4(2):155-9.
Zal F, Mostafavi-Pour Z, Amini F, Heidari A. Effect of vitamin E and C supplements on lipid peroxidation and GSH-dependent antioxidant enzyme status in the blood of women consuming oral contraceptives. Contraception. 2012;86(1):62-6.
Li X, Song Q-S, Wang J-Y, Leng H-j, Chen Z-Q, Liu Z-J, Dang G-T, Song C-L. Simvastatin induces estrogen receptor-alpha expression in bone, restores bone loss, and decreases ERα expression and uterine wet weight in ovariectomized rats. J Bone Miner Metab. 2011;29(4):396-403.
Dickinson DA, Forman HJ. Glutathione in defense and signaling. Ann N Y Acad Sci. 2002;973(1):488-504.
Arslan A, Orkun S, Aydin G, Keles I, Tosun A, Arslan M, Caglayan O. Effects of ovariectomy and ascorbic acid supplement on oxidative stress parameters and bone mineral density in rats. Libyan J Med. 2011;6(1):5965.
Vakili S, Savardashtaki A, Moghaddam MAM, Nowrouzi P, Shirazi MK, Ebrahimi G. The effects of saffron consumption on lipid profile, liver enzymes, and oxidative stress in male hamsters with high fat diet. Trends Pharmacol Sci. 2017;3(3):201-8.
Tabrizi R, Vakili S, Akbari M, Mirhosseini N, Lankarani KB, Rahimi M, Mobini M, Jafarnejad S, Vahedpoor Z, Asemi Z. The effects of curcumin‐containing supplements on biomarkers of inflammation and oxidative stress: A systematic review and meta‐analysis of randomized controlled trials. Phytother Res. 2019;33(2):253-62.
Manolagas SC. Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocr Rev. 2000;21(2):115-37.
Bird R, Draper H. Effect of malonaldehyde and acetaldehyde on cultured mammalian cells: Growth, morphology, and synthesis of macromolecules. J Toxicol Environ Health. 1980;6(4):811-23.
Mada SB, Reddi S, Kumar N, Kumar R, Kapila S, Kapila R, Trivedi R, Karvande A, Ahmad N. Antioxidative peptide from milk exhibits antiosteopenic effects through inhibition of oxidative damage and bone-resorbing cytokines in ovariectomized rats. Nutrition. 2017;43:21-31.
Lamas AZ, Caliman IF, Dalpiaz PLM, de Melo Jr AF, Abreu GR, Lemos EM, Gouvea SA, Bissoli NS. Comparative effects of estrogen, raloxifene and tamoxifen on endothelial dysfunction, inflammatory markers and oxidative stress in ovariectomized rats. Life Sci. 2015;124:101-9.
Moreira AC, Silva AM, Branco AF, Baldeiras I, Pereira GC, Seiça R, Santos MS, Sardão VA. Phytoestrogen coumestrol improves mitochondrial activity and decreases oxidative stress in the brain of ovariectomized Wistar-Han rats. J Funct Foods. 2017;34:329-39.
Delrobaei F, Fatemi I, Shamsizadeh A, Allahtavakoli M. Ascorbic acid attenuates cognitive impairment and brain oxidative stress in ovariectomized mice. Pharmacol Rep. 2019;71(1):133-8.
Arts MJ, Dallinga JS, Voss H-P, Haenen GR, Bast A. A new approach to assess the total antioxidant capacity using the TEAC assay. Food Chem. 2004;88(4):567-70.
Dong Y-s, Wang J-l, Feng D-y, Qin H-z, Wen H, Yin Z-m, Gao G-d, Li C. Protective effect of quercetin against oxidative stress and brain edema in an experimental rat model of subarachnoid hemorrhage. Int J Med Sci. 2014;11(3):282.
Coskun O, Kanter M, Korkmaz A, Oter S. Quercetin, a flavonoid antioxidant, prevents and protects streptozotocin-induced oxidative stress and β-cell damage in rat pancreas. Pharmacol Res. 2005;51(2):117-23.
Liang W, Luo Z, Ge S, Li M, Du J, Yang M, Yan M, Ye Z, Luo Z. Oral administration of quercetin inhibits bone loss in rat model of diabetic osteopenia. Eur J Pharmacol. 2011;670(1):317-24.
Zingg J-M. Vitamin E: an overview of major research directions. Mol Aspects Med. 2007;28(5-6):400-22.
Hamza RZ, Al-Harbi MS, El-Shenawy NS. Ameliorative effect of vitamin E and selenium against oxidative stress induced by sodium azide in liver, kidney, testis and heart of male mice. Biomed Pharmacother. 2017;91:602-10.
Arita M, Sato Y, Arai H, Inoue K. Binding of α‐tocopherylquinone, an oxidized form of α‐tocopherol, to glutathione‐S‐transferase in the liver cytosol. FEBS Lett. 1998;436(3):424-6.
Deng L, Ding Y, Peng Y, Wu Y, Fan J, Li W, Yang R, Yang M, Fu Q. γ-Tocotrienol protects against ovariectomy-induced bone loss via mevalonate pathway as HMG-CoA reductase inhibitor. Bone. 2014;67:200-7.
Macdonald HM, New SA, Golden MH, Campbell MK, Reid DM. Nutritional associations with bone loss during the menopausal transition: evidence of a beneficial effect of calcium, alcohol, and fruit and vegetable nutrients and of a detrimental effect of fatty acids. Am J Clin Nutr. 2004;79(1):155-65.
Wolf RL, Cauley JA, Pettinger M, Jackson R, Lacroix A, Leboff MS, Lewis CE, Nevitt MC, Simon JA, Stone KL. Lack of a relation between vitamin and mineral antioxidants and bone mineral density: results from the Women’s Health Initiative. Am J Clin Nutr. 2005;82(3):581-8.
Ranilla LGl, Genovese MI, Lajolo FM. Effect of different cooking conditions on phenolic compounds and antioxidant capacity of some selected Brazilian bean (Phaseolus vulgaris L.) cultivars. J Agric Food Chem. 2009;57(13):5734-42.
Buchner N, Krumbein A, Rohn S, Kroh LW. Effect of thermal processing on the flavonols rutin and quercetin. Rapid Commun Mass Spectrom. 2006;20(21):3229-35.
Pękal A, Biesaga M, Pyrzynska K. Interaction of quercetin with copper ions: complexation, oxidation and reactivity towards radicals. Biometals. 2011;24(1):41-9.
Fabre G, Bayach I, Berka K, Paloncýová M, Starok M, Rossi C, Duroux J-L, Otyepka M, Trouillas P. Synergism of antioxidant action of vitamins E, C and quercetin is related to formation of molecular associations in biomembranes. Chem Commun. 2015;51(36):7713-6.
Prabu SM, Shagirtha K, Renugadevi J. Quercetin in combination with vitamins (C and E) improve oxidative stress and hepatic injury in cadmium intoxicated rats. Prev Nutr Food Sci. 2011;1(1):1-7.
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