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Betaine Elevates Ovarian Antioxidant Enzyme Activities and Demonstrates Methyl Donor Effect in Non-Pregnant Rats

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Abstract

Chronic alcoholism leads to infertility in male and female rats, and antioxidant enzymes form the first line against oxidative stress in organisms. In recent years, betaine has shown beneficial effects on various tissues, and this study has attempted to clarify antioxidant and methyl donor properties of betaine in the rat ovary. For this purpose, the sexually matured Sprague-Dawley female rats were divided into Control, Ethanol (EtOH), Betaine, and Betaine + EtOH groups. Administration of betaine in Betaine + EtOH group significantly increased CAT activity when compared to the other groups (P < 0.05). GPx activity increased significantly in Betaine and Betaine + EtOH groups as compared to controls (P < 0.05). Interestingly, GPx and CAT activities insignificantly increased (in order compensatory) in EtOH group to suppress oxidative stress. In contrast, SOD activity decreased insignificantly in EtOH group compared to Betaine + EtOH and control groups (P > 0.05). TBARS concentration (as a lipid peroxidation marker) significantly increased in ethanol-treated rats as compared to controls, while total homocysteine concentration significantly decreased in betaine-treated rats in comparison with EtOH group. Regarding to oestrous cycles, ethanol-treated animals had irregular estral cycle and persistent oestrous phase compared to controls and betaine-treated rats. In conclusion, these results demonstrate for the first time the antioxidant and methyl donor properties of betaine in the rat ovary. Thus, betaine might be used as a potential therapy in hyperhomocysteinemia and partial infertility mediated by oxidative stress in females.

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References

  • Agarwal A, Prabakaran SA, Said TM (2005) Prevention of oxidative stress injury to sperm. J Androl 26(6):654–660

    Article  PubMed  CAS  Google Scholar 

  • Alirezaei M, Saeb M, Javidnia K, Nazifi S, Khalighyan N, Saeb S (2010) Betaine reduction of hyperhomocysteinemia and enhancement of 5-hydroxyindoleacetic acid in ethanol-induced hyperhomocysteinemia in rabbits. Afr J Biochem Res 4(11):246–254

    CAS  Google Scholar 

  • Alirezaei M, Jelodar G, Niknam P, Ghayemi Z, Nazifi S (2011a) Betaine prevents ethanol-induced oxidative stress and reduces total homocysteine in the rat cerebellum. J Physiol Biochem 67:605–612

    Article  PubMed  CAS  Google Scholar 

  • Alirezaei M, Saeb M, Javidnia K, Nazifi S, Saeb S (2011b) Hyperhomocysteinemia reduction in ethanol-fed rabbits by oral betaine. Comp Clin Pathol 21:1–7

    Google Scholar 

  • Alirezaei M, Jelodar G, Ghayemi Z (2012a) Antioxidant defense of betaine against oxidative stress induced by ethanol in the rat testes. Int J Pept Res Ther doi:10.1007/s10989-012-9297-9

  • Alirezaei M, Kheradmand A, Heydari R, Tanideh N, Neamati S, Rashidipour M (2012b) Oleuropein protects against ethanol-induced oxidative stress and modulates sperm quality in the rat testis. Mediterr J Nutr Metab. doi:10.1007/s12349-011-0079-2

    Google Scholar 

  • Barak AJ, Beckenhauer HC (1988) The influence of ethanol on hepatic transmethylation. Alcohol Alcohol 23(1):73–77

    PubMed  CAS  Google Scholar 

  • Barak AJ, Beckenhauer HC, Tuma DJ (1985) Ethanol feeding inhibits the activity of hepatic N5-methyltetrahydrofolate: homocysteine methyltransferase in the rat. IRCS Med Sci 13:760–761

    CAS  Google Scholar 

  • Bleich S, Degner D, Sperling W, Bönsch D, Thürauf N, Kornhuber J (2004) Homocysteine as a neurotoxin in chronic alcoholism. Prog Neuropsychopharmacol Biol Psychiatry 28(3):453–464

    Article  PubMed  CAS  Google Scholar 

  • Bo WJ, Krueger WA, Ruenen PK, Symmes SK (1982) Ethanol-induced alterations in the morphology and function of the rat ovary. Anat Rec 202(2):255–260

    Article  PubMed  CAS  Google Scholar 

  • Chuffa LGA, Padovani CR, Martinez FE (2009) Ovarian structure and hormonal status of the UChA and UChB adult rats in response to ethanol. Maturitas 62(1):21–29

    Article  PubMed  CAS  Google Scholar 

  • Claiborne A (1985) Catalase activity. In: Greenwald RA (ed) CRC hand book of methods for oxygen radical research, vol 1. CRC Press, Boca Raton, pp 283–284

    Google Scholar 

  • Dinu D, Nechifor MT, Movileanu L (2006) Ethanol-induced alterations of the antioxidant defense system in rat kidney. J Biochem Mol Toxicol 19(6):386–395

    Article  Google Scholar 

  • Dupont I, Bodenez P, Berthou F, Simon B, Bardou LG, Lucas D (2000) Cytochrome P-450 2E1 activity and oxidative stress in alcoholic patients. Alcohol Alcohol 35(1):98–103

    PubMed  CAS  Google Scholar 

  • Ebisch IMW, Thomas CMG, Peters WHM, Braat DDM, Steegers-Theunissen RPM (2007) The importance of folate, zinc and antioxidants in the pathogenesis and prevention of subfertility. Hum Reprod update 13(2):163–174

    Article  PubMed  CAS  Google Scholar 

  • Finkelstein JD (2007) Metabolic regulatory properties of S-adenosylmethionine and S-adenosylhomocysteine. Clin Chem Lab Med 45(12):1694–1699

    Article  PubMed  CAS  Google Scholar 

  • Forges T, Monnier-Barbarino P, Alberto JM, Gueant-Rodriguez RM, Daval JL, Gueant JL (2007) Impact of folate and homocysteine metabolism on human reproductive health. Hum Reprod update 13(3):225–239

    Article  PubMed  CAS  Google Scholar 

  • Ganesan B, Buddhan S, Anandan R, Sivakumar R, Anbinezhilan R (2010) Antioxidant defense of betaine against isoprenaline-induced myocardial infarction in rats. Mol Biol Rep 37(3):1319–1327

    Google Scholar 

  • Golbahar J, Aminzadeh MA, Hamidi SA, Omrani GR (2005) Association of red blood cell 5-methyltetrahydrfoate folate with bone mineral density in postmenopausal Iranian women. Osteoporos Int 16(12):1894–1898

    Article  PubMed  CAS  Google Scholar 

  • Greenfeld CR, Pepling ME, Babus JK, Furth PA, Flaws JA (2007) BAX regulates follicular endowment in mice. Reproduction 133(5):865–876

    Article  PubMed  CAS  Google Scholar 

  • Hakim RB, Gray RH, Zacur H (1998) Alcohol and caffeine consumption and decreased fertility. Fertil Steril 70(4):632–637

    Article  PubMed  CAS  Google Scholar 

  • Harlap S, Shiono PH (1980) Alcohol, smoking, and incidence of spontaneous abortions in the first and second trimester. Lancet 316(8187):173–176

    Article  Google Scholar 

  • Hugues JN, Coste T, Perret G, Jayle MF, Sebaoun J, Modigliani E (1980) Hypothalamic pituitary ovarian function in thirty-one women with chronic alcoholism. Clin Endocrinol 12(6):543–551

    Article  CAS  Google Scholar 

  • Husain K, Scott BR, Reddy SK, Somani SM (2001) Chronic ethanol and nicotine interaction on rat tissue antioxidant defense system. Alcohol 25(2):89–97

    Article  PubMed  CAS  Google Scholar 

  • Ji C, Kaplowitz N (2003) Betaine decreases hyperhomocysteinemia, endoplasmic reticulum stress, and liver injury in alcohol-fed mice. Gastroenterology 124(5):1488–1499

    Article  PubMed  CAS  Google Scholar 

  • Jozwik M, Wolczynski S, Szamatowicz M (1999) Oxidative stress markers in preovulatory follicular fluid in humans. Mol Hum Reprod 5(5):409–413

    Article  PubMed  CAS  Google Scholar 

  • Kage DN, Malashetty VB, Seetharam YN, Suresh P, Patil SB (2009) Effect of ethanol extract of whole plant of Trichosanthes cucumerina var. cucumerina L. on gonadotropins, ovarian follicular kinetics and ooestrous cycle for screening of antifertility activity in albino rats. J Morphol 27(1):173–182

    Google Scholar 

  • Karthikeyan G, Thachil A, Sharma S, Kalaivani M, Ramakrishnan L (2007) Elevated high sensitivity CRP levels in patients with mitral stenosis and left atrial thrombus. Int J Cardiol 122(3):252–254

    Article  PubMed  Google Scholar 

  • Kheradmand A, Alirezaei M, Asadian P, Alavi ER, Joorabi S (2009) Antioxidant enzyme activity and MDA level in the rat testis following chronic administration of ghrelin. Andrologia 41(6):335–340

    Article  PubMed  CAS  Google Scholar 

  • Kheradmand A, Alirezaei M, Birjandi M (2010) Ghrelin promotes antioxidant enzyme activity and reduces lipid peroxidation in the rat ovary. Regul Pept 162(1–3):84–89

    Article  PubMed  CAS  Google Scholar 

  • Kheradmand A, Dezfoulian O, Alirezaei M, Rasoulian B (2012) Ghrelin modulates testicular germ cells apoptosis and proliferation in adult normal rats. Biochem Biophys Res Commun 419:299–304

    Article  PubMed  CAS  Google Scholar 

  • Kim HP, Roe JH, Chock PB, Yim MB (1999) Transcriptional activation of the human manganese superoxide dismutase gene mediated by tetradecanoylphorbol acetate. J Biol Chem 274(52):37455–37460

    Article  PubMed  CAS  Google Scholar 

  • Kinney A, Kline J, Kelly A, Reuss ML, Levin B (2007) Smoking, alcohol and caffeine in relation to ovarian age during the reproductive years. Hum Reprod 22(4):1175–1185

    Article  PubMed  CAS  Google Scholar 

  • Krueger WA, Bo WJ, Kevin Rudeen P (1982) Female reproduction during chronic ethanol consumption in rats. Pharmacol Biochem Behav 17(4):629–631

    Article  PubMed  CAS  Google Scholar 

  • Li SY, Gomelsky M, Duan J, Zhang Z, Gomelsky L, Zhang X, Epstein PN, Ren J (2004) Overexpression of aldehyde dehydrogenase-2 (ALDH2) transgene prevents acetaldehyde-induced cell injury in human umbilical vein endothelial cells. J Biol Chem 279(12):11244–11252

    Article  PubMed  CAS  Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193(1):265–275

    PubMed  CAS  Google Scholar 

  • Margolin Y, Aten RF, Behrman HR (1990) Antigonadotropic and antisteroidogenic actions of peroxide in rat granulosa cells. Endocrinology 127(1):245–250

    Article  PubMed  CAS  Google Scholar 

  • Masella R, Vari R, D’Archivio M, Di Benedetto R, Matarrese P, Malorni W, Scazzocchio B, Giovannini C (2004) Extra virgin olive oil biophenols inhibit cell-mediated oxidation of LDL by increasing the mRNA transcription of glutathione-related enzymes. J Nutr 134(4):785–791

    PubMed  CAS  Google Scholar 

  • Mates JM (2000) Effects of antioxidant enzymes in the molecular control of reactive oxygen species toxicology. Toxicology 153(1):83–104

    Article  PubMed  CAS  Google Scholar 

  • Mello NK, Bree MP, Mendelson JH, Ellingboe J, King NW, Sehgal P (1983) Alcohol self-administration disrupts reproductive function in female macaque monkeys. Science 221(4611):677–679

    Article  PubMed  CAS  Google Scholar 

  • Mello NK, Mendelson JH, Teoh SK (1993) Overview of the effects of alcohol on the neuroendocrine function in women. Alcohol and the endocrine system. National Institute on Alcohol Abuse and Alcoholism Research monograph 23:139–169

    Google Scholar 

  • Millian NS, Garrow TA (1998) Human betaine-homocysteine methyltransferase is a zinc metalloenzyme. Arch Biochem Biophys 356(1):93–98

    Article  PubMed  CAS  Google Scholar 

  • Neamati S, Alirezaei M, Kheradmand A (2011) Ghrelin acts as an antioxidant agent in the rat kidney. Int J Pept Res Ther 17:239–245

    Article  CAS  Google Scholar 

  • Nicotera TM, Notaro J, Notaro S, Schumer J, Sandberg AA (1989) Elevated superoxide dismutase in Bloom’s syndrome: a genetic condition of oxidative stress. Cancer Res 49(19):5239–5243

    PubMed  CAS  Google Scholar 

  • Paszkowski T, Traub AI, Robinson SY, McMaster D (1995) Selenium dependent glutathione peroxidase activity in human follicular fluid. Clin Chim Acta 236(2):173–180

    Article  PubMed  CAS  Google Scholar 

  • Petrie L, Duthie SJ, Rees WD, McConnell JML (2002) Serum concentrations of homocysteine are elevated during early pregnancy in rodent models of fetal programming. Br J Nutr 88(05):471–477

    Article  PubMed  CAS  Google Scholar 

  • Pettersson P, Ellsinger BM, Sjoberg C, Bjorntorp P (1990) Fat distribution and steroid hormones in women with alcohol abuse. J Int Med 228(4):311–316

    Article  CAS  Google Scholar 

  • Rees WD, Wilson FA, Maloney CA (2006) Sulfur amino acid metabolism in pregnancy: the impact of methionine in the maternal diet. J Nutr 136(6):1701S–1705S

    PubMed  CAS  Google Scholar 

  • Rodriguez C, Mayo JC, Sainz RM, Antolinn I, Herrera F, Martin V, Reiter RJ (2004) Regulation of antioxidant enzymes: a significant role for melatonin. J Pineal Res 36(1):1–9

    Article  PubMed  CAS  Google Scholar 

  • Rueda BR, Tilly KI, Hansen TR, Hoyer PB, Tilly JL (1995) Expression of superoxide dismutase, catalase and glutathione peroxidase in the bovine corpus luteum: evidence supporting a role for oxidative stress in luteolysis. Endocrine 3(3):227–232

    Article  PubMed  CAS  Google Scholar 

  • Schwahn BC, Laryea MD, Chen Z, Melnyk S, Pogribny I, Garrow T, James SJ, Rozen R (2004) Betaine rescue of an animal model with methylenetetrahydrofolate reductase deficiency. Biochem J 382(Pt 3):831

    PubMed  CAS  Google Scholar 

  • Sehirli O, Sener E, Sener G, Cetinel S, Erzik C, Yegen BC (2008) Ghrelin improves burn-induced multiple organ injury by depressing neutrophil infiltration and the release of pro-inflammatory cytokines. Peptides 29(7):1231–1240

    Article  PubMed  CAS  Google Scholar 

  • Slow S, Lever M, Chambers ST, George PM (2009) Plasma dependent and independent accumulation of betaine in male and female rat tissues. Physiol Res 58:403–410

    PubMed  CAS  Google Scholar 

  • Song Z, Zhou Z, Chen T, Hill D, Kang J, Barve S, McClain C (2003) S-adenosylmethionine (SAMe) protects against acute alcohol induced hepatotoxicity in mice. J Nutr Biochem 14(10):591–597

    Article  PubMed  CAS  Google Scholar 

  • Subbarao KV, Richardson JS, Ang LC (1990) Autopsy samples of Alzheimer’s cortex show increased peroxidation in vitro. J Neurochem 55(1):342–345

    Article  PubMed  CAS  Google Scholar 

  • Sugino N, Takiguchi S, Kashida S, Takayama H, Yamagata Y, Nakamura Y, Kato H (1999) Suppression of intracellular superoxide dismutase activity by antisense oligonucleotides causes inhibition of progesterone production by rat luteal cells. Biol Reprod 61(4):1133–1138

    Article  PubMed  CAS  Google Scholar 

  • Sunden SLF, Renduchintala MS, Park EI, Miklasz SD, Garrow TA (1997) Betaine-homocysteine methyltransferase expression in porcine and human tissues and chromosomal localization of the human gene. Arch Biochem Biophys 345(1):171–174

    Article  PubMed  CAS  Google Scholar 

  • Tremellen K (2008) Oxidative stress and male infertility-a clinical perspective. Hum Reprod Update 14(3):243–259

    Article  PubMed  CAS  Google Scholar 

  • Trisolini C, Minoia G, Manca R, Rizzo A, Robbe D, Valentini L, Sciorsci RL (2008) Plasma homocysteine levels in cycling, pregnant, and spayed bitches. Anim Reprod Sci 108(1):29–36

    Article  PubMed  CAS  Google Scholar 

  • Tsai-Turton M, Luderer U (2006) Opposing effects of glutathione depletion and follicle-stimulating hormone on reactive oxygen species and apoptosis in cultured preovulatory rat follicles. Endocrinology 147(3):1224–1236

    Article  PubMed  CAS  Google Scholar 

  • Valimaki M, Pelkonen R, Salaspuro M, Harkonenen M, Hirvonen E, Ylikahri R (1984) Sex hormones in amenorrheic women with alcoholic liver disease. J Clin Endocrinol Metab 59(1):133–138

    Article  PubMed  CAS  Google Scholar 

  • Valimaki MJ, Laitinen K, Tiitinen A, Steman UH, Ylostao P (1995) Gonadal function and morphology in non-cirrhotic female alcoholics. Acta Obstet Gynecol Scand 74(6):462–466

    Article  PubMed  CAS  Google Scholar 

  • Van Thiel DH, Gavaler JS, Lester R, Sherins RJ (1978) Alcohol-induced ovarian failure in the rat. J Clin Invest 61(3):624

    Article  PubMed  Google Scholar 

  • Wallace JMW, Bonham MP, Strain JJ, Duffy EM, Robson PJ, Ward M, McNulty H, Davidson PW, Myers GJ, Shamlaye CF (2008) Homocysteine concentration, related B vitamins, and betaine in pregnant women recruited to the Seychelles Child Development Study. Am J Clin Nutr 87(2):391–397

    PubMed  CAS  Google Scholar 

  • Yao P, Li K, Song F, Zhou S, Sun X, Zhang X, Nussler AK, Liu L (2007) Heme oxygenase-1 upregulated by Ginkgo biloba extract: potential protection against ethanol-induced oxidative liver damage. Food Chem Toxicol 45(8):1333–1342

    Article  PubMed  CAS  Google Scholar 

  • Yoo HY, Chang MS, Rho HM (1999) The activation of the rat copper/zinc superoxide dismutase gene by hydrogen peroxide through the hydrogen peroxide-responsive element and by paraquat and heat shock through the same heat shock element. J Biol Chem 274(34):23887–23892

    Article  PubMed  CAS  Google Scholar 

  • Zeisel SH, Mar MH, Howe JC, Holden JM (2003) Concentrations of choline-containing compounds and betaine in common foods. J Nutr 133(5):1302–1307

    PubMed  CAS  Google Scholar 

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Acknowledgment

This research was financially supported by School of Veterinary Medicine-Shiraz University, Shiraz, Iran. We are most grateful to Saeedeh Ahmadi for the kind technical assistance; also like to thank M. Shoaei and R. Shirazi (the member and manager of Aryadalman Company, Tehran, Iran) for providing betaine (Betafine®).

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  1. Division of Biochemistry, School of Veterinary Medicine, Lorestan University, P.O. Box 465, Khorram Abad, Iran

    Masoud Alirezaei

  2. Department of Physiology, School of Veterinary Medicine, Shiraz University, 71345, Shiraz, Iran

    Parvin Niknam & Gholamali Jelodar

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  1. Masoud Alirezaei
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Correspondence to Masoud Alirezaei.

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Alirezaei, M., Niknam, P. & Jelodar, G. Betaine Elevates Ovarian Antioxidant Enzyme Activities and Demonstrates Methyl Donor Effect in Non-Pregnant Rats. Int J Pept Res Ther 18, 281–290 (2012). https://doi.org/10.1007/s10989-012-9300-5

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