Skip to main content
SpringerLink
Log in

Palm tocotrienol-rich fraction reduced plasma homocysteine and heart oxidative stress in rats fed with a high-methionine diet

  • Original Paper
  • Published:
Journal of Physiology and Biochemistry Aims and scope Submit manuscript

Abstract

Oxidative stress contributes to cardiovascular diseases. We aimed to study the effects of palm tocotrienol-rich fraction (TRF) on plasma homocysteine and cardiac oxidative stress in rats fed with a high-methionine diet. Forty-two male Wistar rats were divided into six groups. The first group was the control. Groups 2–6 were fed 1 % methionine diet for 10 weeks. From week 6 onward, folate (8 mg/kg diet) or palm TRF (30, 60 and 150 mg/kg diet) was added into the diet of groups 3, 4, 5 and 6. The rats were then killed. Palm TRF at 150 mg/kg and folate supplementation prevented the increase in plasma total homocysteine (4.14 ± 0.33 and 4.30 ± 0.26 vs 5.49 ± 0.25 mmol/L, p < 0.05) induced by a high-methionine diet. The increased heart thiobarbituric acid reactive substance in rats fed with high-methionine diet was also prevented by the supplementations of palm TRF (60 and 150 mg/kg) and folate. The high-methionine group had a lower glutathione peroxidase activity (49 ± 3 vs 69 ± 4 pmol/mg protein/min) than the control group. This reduction was reversed by palm TRF at 60 and 150 mg/kg diet (p < 0.05), but not by folate. Catalase and superoxide dismutase activities were unaffected by both methionine and vitamin supplementations. In conclusion, palm TRF was comparable to folate in reducing high-methionine diet-induced hyperhomocysteinemia and oxidative stress in the rats’ hearts. However, palm TRF was more effective than folate in preserving the heart glutathione peroxidase enzyme activity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Achón M, Alonso-Aperte E, Ubeda N, Varela-Moreiras G (2007) Supranormal dietary folic acid supplementation: effects on methionine metabolism in weanling rats. Br J Nutr 98:490–496

    Article  PubMed  Google Scholar 

  2. Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126

    Article  PubMed  CAS  Google Scholar 

  3. Ajuluchukwu JN, Okubadejo NU, Mabayoje M, Ojini FI, Okwudiafor RN, Mbakwem AC, Fasanmade OA, Oke DA (2007) Comparative study of the effect of tocotrienols and -tocopherol on fasting serum lipid profiles in patients with mild hypercholesterolaemia: a preliminary report. Niger Postgrad Med J 14:30–33

    PubMed  CAS  Google Scholar 

  4. Asmadi AY, Adam A, Wan Ngah WZ, Norazlina M, Kamisah Y, Nur-Azlina MF, Qodriyah MS, Ahmad NS, Gapor MT, Marzuki A (2005) Tocotrienols and α-tocopherol reduced acute and chronic lung lipid peroxidation induced by paraquat in rats. Pakistan J Nutr 4:97–100

    Article  Google Scholar 

  5. Beyer WF Jr, Fridovich I (1987) Assaying for superoxide dismutase activity: some large consequences of minor changes in conditions. Anal Biochem 161:559–566

    Article  PubMed  CAS  Google Scholar 

  6. Chang L, Geng B, Yu F, Zhao J, Jiang H, Du J, Tang C (2008) Hydrogen sulfide inhibits myocardial injury induced by homocysteine in rats. Amino Acids 34:573–585

    Article  PubMed  CAS  Google Scholar 

  7. da Cunha AA, Scherer E, da Cunha MJ, Schmitz F, Machado FR, Lima DD, Delwing D, Wyse AT (2012) Acute hyperhomocysteinemia alters the coagulation system and oxidative status in the blood of rats. Mol Cell Biochem 360:205–214

    Article  PubMed  CAS  Google Scholar 

  8. Das M, Das S, Wang P, Powell SR, Das DK (2008) Caveolin and proteasome in tocotrienol mediated myocardial protection. Cell Physiol Biochem 22:287–294

    Article  PubMed  CAS  Google Scholar 

  9. Das S, Lekli I, Das M, Szabo G, Varadi J, Juhasz B, Bak I, Nesaretam K, Tosaki A, Powell SR, Das DK (2008) Cardioprotection with palm oil tocotrienols: comparison of different isomers. Am J Physiol Heart Circ Physiol 294:H970–H978

    Article  PubMed  CAS  Google Scholar 

  10. Das S, Mukherjee S, Lekli I, Gurusamy N, Bardhan J, Raychoudhury U, Chakravarty R, Banerji S, Knowlton AA, Das DK (2012) Tocotrienols confer resistance to ischemia in hypercholesterolemic hearts: insight with genomics. Mol Cell Biochem 360:35–45

    Article  PubMed  CAS  Google Scholar 

  11. Gapor MT, Leong WL, Ong ASH, Kawada T, Watanabe H and Tsuchiya N. Production of high concentration tocopherols and tocotrienols from palm oil byproducts. US Patent No. 5,190,618. 2 March 1993; Malaysian Patent No. MY-110779-A

  12. Gatt A, Makris M (2007) Hyperhomocysteinemia and venous thrombosis. Semin Hematol 44:70–76

    Article  PubMed  CAS  Google Scholar 

  13. Handy DE, Zhang Y, Loscalzo J (2005) Homocysteine down-regulates cellular glutathione peroxidase (GPx1) by decreasing translation. J Biol Chem 280:15518–15525

    Article  PubMed  CAS  Google Scholar 

  14. Hao CN, Geng YJ, Li F, Yang T, Su DF, Duan JL, Li Y (2011) Insulin-like growth factor-1 receptor activation prevents hydrogen peroxide-induced oxidative stress, mitochondrial dysfunction and apoptosis. Apoptosis 16:1118–1127

    Article  PubMed  CAS  Google Scholar 

  15. Heinz J, Kropf S, Luley C, Dierkes J (2009) Homocysteine as a risk factor for cardiovascular disease in patients treated by dialysis: a meta-analysis. Am J Kidney Dis 54:478–489

    Article  PubMed  CAS  Google Scholar 

  16. Hidiroglou N, Gilani GS, Long L, Zhao X, Madere R, Cockell K, Belonge B, Ratnayake WMN, Peace R (2004) The influence of dietary vitamin E, fat, and methionine on blood cholesterol profile, homocysteine levels, and oxidizability of low density lipoprotein in the gerbil. J Nutr Biochem 15:730–740

    Article  PubMed  CAS  Google Scholar 

  17. Huang RFS, Hsu YC, Lin HL, Yang FL (2001) Folate depletion and elevated plasma homocysteine promote oxidative stress in rat livers. J Nutr 131:33–38

    PubMed  CAS  Google Scholar 

  18. Hwang SY, Siow YL, Au-Yeung KK, House J, Karmin O (2011) Folic acid supplementation inhibits NADPH oxidase-mediated superoxide anion production in the kidney. Am J Physiol Renal Physiol 300:F189–F198

    Article  PubMed  CAS  Google Scholar 

  19. Ibrahim W, Tousson E, Ali EM, Mansour MA (2011) Folic acid alleviates oxidative stress and hyperhomocysteinemia involved in testicular dysfunction of hypothyroid rats. Gen Comp Endocrinol 174:143–149

    Article  PubMed  CAS  Google Scholar 

  20. Joseph J, Joseph L, Devi S, Kennedy RH (2008) Effect of anti-oxidant treatment on hyperhomocysteinemia-induced myocardial fibrosis and diastolic dysfunction. J Heart Lung Transplant 27:1237–1241

    Article  PubMed  Google Scholar 

  21. Kamisah Y, Norhayati MY, Zakri B, Asmadi AY (2009) The effects of palmvitee on δ-aminolevulinic acid-induced hyperbilirubinaemia in suckling rats. Arch Med Sci 5:329–334

    CAS  Google Scholar 

  22. Kolling J, Scherer EB, da Cunha AA, da Cunha MJ, Wyse AT (2010) Homocysteine induces oxidative-nitrative stress in heart of rats: prevention by folic acid. Cardiovasc Toxicol 11:67–73

    Article  Google Scholar 

  23. Lawrence RA, Burk RF (1976) Glutathione peroxidase activity in selenium-deficient rat liver. Biochem Biophys Res Commun 71:952–958

    Article  PubMed  CAS  Google Scholar 

  24. Ledwozyw A, Michalak J, Stepien A, Kadziolka A (1986) The relationship between plasma triglycerides, cholesterol, total lipids and lipid peroxidation products during human atherosclerosis. Clin Chem Acta 155:275–284

    Article  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  26. Mates JM, Christina PG, Ignacio NDC (1999) Antioxidant enzymes and human diseases. Clin Biochem 32:595–603

    Article  PubMed  CAS  Google Scholar 

  27. McAnulty SR, McAnulty LS, Nieman DC, Morrow JD, Shooter LA, Holmes S, Heward C, Henson DA (2005) Effect of alpha-tocopherol supplementation on plasma homocysteine and oxidative stress in highly trained athletes before and after exhaustive exercise. J Nutr Biochem 16:530–537

    Article  PubMed  CAS  Google Scholar 

  28. Mendes RH, Sirvente RA, Candido GO, Mostarda C, Salemi VMC, D’Almeida V, Jacob MH, Ribeiro MF, Bello-Klein A, Rigato K, Irigoyen MC (2010) Homocysteine thiolactone induces cardiac dysfunction: role of oxidative stress. J Cardiovasc Pharmacol 55:198–202

    Article  PubMed  CAS  Google Scholar 

  29. Ministry of Health Malaysia. Number of discharges and deaths in government hospitals. Information and Documentation System Unit. 2008

  30. Pajares MA, Pérez-Sala D (2006) Betaine homocysteine S-methyltransferase: just a regulator of homocysteine metabolism? Cell Mol Life Sci 63:2792–2803

    Article  PubMed  CAS  Google Scholar 

  31. Pexa A, Herrmann M, Taban-Shomal O, Henle T, Deussen A (2009) Experimental hyperhomocysteinaemia: differences in tissue metabolites between homocystine and methionine feeding in a rat model. Acta Physiol (Oxf) 197:27–34

    Article  CAS  Google Scholar 

  32. Qipshidze N, Tyagi N, Sen U, Givvimani S, Metreveli N, Lominadze D, Tyagi SC (2010) Folic acid mitigated cardiac dysfunction by normalizing the levels of tissue inhibitor of metalloproteinase and homocysteine-metabolizing enzymes postmyocardial infarction in mice. Am J Physiol Heart Circ Physiol 299:H1484–H1493

    Article  PubMed  CAS  Google Scholar 

  33. Racek J, Rusnakova H, Trefil L, Siala KK (2005) The influence of folate and antioxidants on homocysteine levels and oxidative stress in patients with hyperlipidemia and hyperhomocysteinemia. Physiol Res 54:87–95

    PubMed  CAS  Google Scholar 

  34. Rasool AH, Rahman AR, Yuen KH, Wong AR (2008) Arterial compliance and vitamin E blood levels with a self emulsifying preparation of tocotrienol rich vitamin E. Arch Pharm Res 31:1212–1217

    Article  PubMed  CAS  Google Scholar 

  35. Rosamond W, Flegal K, Furie K, Go A, Greenlund K, Haase N, Hailpern SM, Ho M, Howard V, Kissela B, Kittner S, Lloyd-Jones D, McDermott M, Meigs J, Moy C, Nichol G, O'Donnell C, Roger V, Sorlie P, Steinberger J, Thom T, Wilson M, Hong Y (2008) American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 117:e25–e146

    Article  PubMed  Google Scholar 

  36. Schnabel R, Lackner KJ, Rupprecht HJ, Espinola-Klein C, Torzewski M, Lubos E, Bickel C, Cambien F, Tiret L, Munzel T, Blankenberg S (2005) Glutathione peroxidase-1 and homocysteine for cardiovascular risk prediction: results from the AtheroGene study. J Am Coll Cardiol 45:1631–1637

    Article  PubMed  CAS  Google Scholar 

  37. Shahram F, Faridar A, Hamedani MG, Nadji A, Naderi N, Mojarad SN, Rasker JJ, Davatchi F (2010) Plasma homocysteine level in patients with Behcet’s disease with or without thrombosis. Arch Iran Med 13:476–481

    PubMed  CAS  Google Scholar 

  38. Sharma M, Rai SK, Tiwari M, Chandra R (2007) Effect of hyperhomocysteinemia on cardiovascular risk factors and initiation of atherosclerosis in Wistar rats. Eur J Pharmacol 574:49–60

    Article  PubMed  CAS  Google Scholar 

  39. Singh AP, Kaur T, SinghDahiya R, Singh N, Singh Bedi PM (2010) Ameliorative role of rosiglitazone in hyperhomocysteinemia-induced experimental cardiac hypertrophy. J Cardiovasc Pharmacol 56:53–59

    Article  PubMed  CAS  Google Scholar 

  40. Wang J, Alexanian A, Ying R, Kizhakekuttu TJ, Dharmashankar K, Vasquez-Vivar J, Gutterman DD, Widlansky ME (2012) Acute exposure to low glucose rapidly induces endothelial dysfunction and mitochondrial oxidative stress: role for AMP kinase. Arterioscler Thromb Vasc Biol 32:712–720

    Article  PubMed  CAS  Google Scholar 

  41. Wang H, Tan H, Yang F (2005) Mechanisms in homocysteine-induced vascular disease. Drug Discov Today 2:25–31

    Article  CAS  Google Scholar 

  42. Wronska-Nofer T, Nofer J, Stetkiewicz J, Wierzbicka M, Bolinska H, Fobker M, Schulte H, Assmann G, Eckardstein A (2007) Evidence for oxidative stress at elevated plasma thiol levels in chronic exposure to carbon disulfide (CS2) and coronary heart disease. Nutr Metab Cardiovasc Dis 17:546–553

    Article  PubMed  CAS  Google Scholar 

  43. Yalçinkaya-Demirsöz S, Depboylu B, Dogru-Abbasoglu S, Unlüçerçi Y, Uysal M (2009) Effects of high methionine diet on oxidative stress in serum, apo-B containing lipoproteins, heart, and aorta in rabbits. Ann Clin Lab Sci 39:386–391

    PubMed  Google Scholar 

  44. Yang RX, Huang SY, Yan FF, Lu XT, Xing YF, Liu Y, Liu YF, Zhao YX (2010) Danshensu protects vascular endothelia in a rat model of hyperhomocysteinemia. Acta Pharmacol Sin 31:1395–1400

    Article  PubMed  CAS  Google Scholar 

  45. Zhang R, Ma J, Xia M, Zhu H, Ling W (2004) Mild hyperhomocysteinemia induced by feeding rats diet rich in methionine or deficient in folate promotes early atherosclerotic inflammatory process. J Nutr 134:825–830

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors would like to thank Puan Azizah Osman for her technical assistance and the Faculty of Medicine Universiti Kebangsaan Malaysia (FF-013-2006) for funding this research project.

Author information

Authors and Affiliations

  1. Department of Basic Medical Sciences, Kuliyyah of Medicine, International Islamic University of Malaysia, Pahang, Malaysia

    Ku-Zaifah Norsidah

  2. Faculty of Traditional and Complementary Medicine, Cyberjaya University College of Medical Sciences, Selangor, Malaysia

    Ahmad Yusof Asmadi

  3. Questra Clinical Research Sdn Bhd, Penang, Malaysia

    Ayob Azizi

  4. Department of Anatomy, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia

    Othman Faizah

  5. Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300, Kuala Lumpur, Malaysia

    Yusof Kamisah

Authors
  1. Ku-Zaifah Norsidah
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ahmad Yusof Asmadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ayob Azizi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Othman Faizah
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yusof Kamisah
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yusof Kamisah.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Norsidah, KZ., Asmadi, A.Y., Azizi, A. et al. Palm tocotrienol-rich fraction reduced plasma homocysteine and heart oxidative stress in rats fed with a high-methionine diet. J Physiol Biochem 69, 441–449 (2013). https://doi.org/10.1007/s13105-012-0226-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13105-012-0226-3

Keywords

Search

Navigation