Tocotrienol Rich Fraction from Palm Oil Reduces Plasma and Erythrocyte Membrane Lipid Alteration in Diabetic Rats: Tocotrienols Reduce Dyslipidemia in Plasma and Erythrocytes

Nasar Alwahaibi, Siti Balkis Budin, Zariyantey Abdul Hamid, Jamaludin Mohamed, Jalifah Latip, Norzamzurina Binti Ismail, Alefee Bin Ayatillah, Fatmah Ali Matough


BACKGROUND: Tocotrienol-rich fraction (TRF) from palm oil has been shown to exhibit potent antioxidative properties in various pathological conditions. This study aimed to determine the antioxidative properties of TRF on the plasma and erythrocyte membrane lipids composition in streptozotocin-induced diabetic rats.

METHODS: Male Sprague-Dawley rats (n=40) were divided randomly into four groups of 10, which were a normal group, a normal group with TRF, a diabetic group, and a diabetic group with TRF. Following four weeks of treatment, lipids compositions in the plasma and erythrocyte membrane were investigated.

RESULTS: TRF significantly reduced the plasma total cholesterol, to that in the diabetic group. In addition, supplementation of TRF was able to reduce the very low density lipoprotein cholesterol (VLDL-C), triglycerides levels in treated diabetic rat although no significant different was observed when compared with untreated diabetic rats alone. Furthermore, TRF supplementation showed increased the levels of phosphatidylinositol, phosphatidylserine, and total phospholipid levels in diabetic rats. However, the linoleic acid (18:2) levels were reduced in diabetic rats compared to the control group, and the eicosadienoic acid (20:2) levels were significantly increased by TRF supplementation in diabetic rats.

CONCLUSION: Supplementation with 200 mg/kg TRF improves dyslipidemia and that TRF, therefore, might have protective effects against oxidative damage of phospholipids. This study also showed the antioxidative properties of TRF on the erythrocyte membrane lipids composition, in particular, its protective effects against peroxidation of unsaturated fatty acids.

KEYWORDS: antioxidative property, cholesterol, fatty acids, phospholipids, tocotrienol-rich fraction

Full Text:



Johansen JS, Harris AK, Rychly DJ, Ergul A. Oxidative stress and the use of antioxidants in diabetes: linking basic science to clinical practice. Cardiovasc Diabet. 2005; 4: 5, CrossRef.

Aprioku JS. Pharmacology of free radicals and the impact of reactive oxygen species on the testis. J Reprod Infertil. 2013; 14: 158-72, PMID.

Shargorodsky M, Matas Z, Zimlichman R. Effect of long-term treatment with antioxidants (vitamin C, vitamin E, coenzyme Q10 and selenium) on arterial compliance, humoral factors and inflammatory markers in patients with multiple cardiovascular risk factors. Nutr Metab. 2010; 7: 55, CrossRef.

Frank D, Chin C, Schrader GP, Eckert G, Rimbach G. Do tocotrienols have potential as neuroprotective dietary factors? Ageing Res Rev. 2012; 11: 163-80, CrossRef.

Wilankara C, Sharmaa D, Checkera R, Khana NM, Patwardhana R, Patilb A, et al. Role of immunoregulatory transcription factors in differential immunomodulatory effects of tocotrienols. Free Radic Biol Med. 2011; 51: 129-43, CrossRef.

Ahsan H, Ahad A, Iqbal J, Siddiqui WA. Pharmacological potential of tocotrienols: a review. Nutr Metab. 2014; 11: 52, CrossRef.

Ito M, Kondo Y, Nakatani A. Naruse A. New model of progressive non-insulin-dependent diabetes mellitus in mice induced by streptozotocin. Biol Pharmacol Bull. 1999; 22: 988-9, CrossRef.

Weiss RB. Streptozotocin: A review of its pharmacology, efficacy and toxicity. Canc Treat Rep 1982; 66: 427-38, PMID.

Smith SB, Prior RL, Mersmann HJ. Interrelationship between insulin and lipid metabolism in normal and alloxan-diabetic cattle. J Nutr. 1983; 113: 1002-15, CrossRef.

Ikebukuro KA, Yasushi Y, Yuichiro F, Shimpei S, Yutaka O, Haruki H, et al. Treatment of streptozotocin-induced diabetes mellitus by transplantation of islet cells plus bone marrow cells via portal vein in rats1. Transplantation. 2002; 73: 512-18, CrossRef.

Budin SB, Yusof KM, Idris MH, Abd Hamid Z, Mohamed J. Tocotrienol-rich fraction of palm oil reduced pancreatic damage and oxidative stress in streptozotocin-induced diabetic rats. Aust J Basic Appl Sci. 2011; 5: 2367-74, article.

Matough FA, Budin SB, Hamid ZA, Mariati AR, Alwahaibi N, Mohamed J. Tocotrienol-rich fraction from palm oil prevents oxidative damage in diabetic rats. Sultan Qaboos Univ Med J. 2014; 14: e95-e103, PMID.

Dodge JT. Composition of phospholipids and of phospholipid fatty acids and aldehydes in human red cells. J Lipid Res. 1967; 8: 667-75, PMID.

Folch J, Stanley S. A simple method for the isolation of total lipids from animal tissues. Biol Chem. 1957; 226: 497-509, PMID.

Patton GM, Fasulo JM, Robins SJ. Separation of phospholipids and individual molecular species of phospholipids by high-performance liquid chromatography. J Lipid Res. 1982; 23: 190-6, PMID.

Morrison WR. Preparation of fatty acid methyl esters and dimethylacetals from lipids with boron fluoride–methanol. J Lipid Res. 1964; 5: 600-8, PMID.

Tynan MB, Nicholls DP, Maguire SM, Steele IC, McMaster C, Moore R, et al. Erythrocyte membrane fatty acid composition as a marker of dietary compliance in hyperlipidaemic subjects. Atherosclerosis. 1995; 117: 245-52, CrossRef.

Roehrs M, Valentini J, Paniz C, Moro A, Charão M, Bulcão R, et al. The relationships between exogenous and endogenous antioxidants with the lipid profile and oxidative damage in hemodialysis patients. BMC Nephrol. 2011; 12: 59-71, CrossRef.

Bitzur R, Cohen H, Kamari Y, Shaish A, Harats D. Triglycerides and HDL cholesterol: stars or second leads in diabetes? Diabetes Care. 2009; 32: S373-S7, CrossRef.

Yuen KH, Wong JW, Lim AB, Ng BH, Choy WP. Effect of mixedtocotrienols in hypercholesterolemic subjects. Funct Foods Health Dis. 2011; 3: 106-17, article.

Pearce BC, Parker RA, Deason ME, Dischino DD, Gillespie E, Qureshi AA, et al. Inhibitors of cholesterol biosynthesis. 2. Hypocholesterolemic and antioxidant activities of benzopyran and tetrahydronaphthalene analogues of the tocotrienols. J Med Chem. 1994; 37: 526-41, CrossRef.

Qureshi AA, Burger WC, Peterson DM, Elson CE. The structure of an inhibitor of cholesterol biosynthesis isolated from barley. J Biol Chem. 1986; 261: 10544-50, PMID.

Shinde S, Suryakar AN, Sontakke AN, More UK. Effect of antioxidant vitamin supplementation on erythrocyte membrane composition in Type I diabetes mellitus in context of oxidative stress. Biomed Res. 2010; 21: 156-60, article.

Aski BS, Devarnavadagi BB, Rudrappa G, Kashinath RT. Influence of anti diabetic therapy on plasma lipid profile and its relation to erythrocyte membrane lipid levels in type 2 diabetic subjects. GJMR. 2012; 2012: 12, article.

Allen JC, Boyd LC, Alston-Mills BP, Fenner GP. Determination of membrane lipid differences in insulin resistant diabetes mellitus type 2 in whites and blacks. Nutrition. 2006; 22: 1096-102, CrossRef.

Qureshi AA, Pearce BC, Nor RM, Gapor A, Peterson DM, Elson CE. Dietary alphatocopherol attenuates the impact of gammatocotrienol on hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in chickens. J Nutr. 1996; 126: 389-94, CrossRef.

Little A, Levy R, Chuaqui-Kidd P, Hand D. A double-blind, placebo controlled trial of high-dose lecithin in Alzheimer's disease. J Neurol Neurosurg Psychiatry. 1985; 48: 736-42, CrossRef.

Labrouche S, Freyburger G, Gin H, Boisseau MR, Cassagne C. Changes in phospholipid composition of blood cell membranes (erythrocyte, platelet, and polymorphonuclear) in different types of diabetes-clinical and biological correlations. Metabolism. 1996; 45: 57-62, CrossRef.

Mueller RB, Pical C. Inositol phospholipid metabolism in Arabidopsis. Characterized and putative isoforms of inositol phospholipid kinase and phosphoinositide-specific phospholipase C. Plant Physiol. 2002; 130: 22-46, CrossRef.

Allen HG. Role of Membrane Lipids in Developing Insulin Resistance Diabetes Mellitus Type II in Caucasians and African Americans [Dissertation]. Raleigh: Faculty of North Carolina State University; 2000, article.

Burgess JW, Boucher J, Tracey AM, Neville PR, Stamler C, Zachariah S, et al. Phosphatidylinositol promotes cholesterol transport and excretion. J Lipid Res. 2003; 44: 1355-61, CrossRef.

Stamler CJ, Breznan D, Neville TA, Viau FJ, Camlioglu E, Sparks DL. Phosphatidylinositol promotes cholesterol transport in vivo. J Lipid Res. 2000; 41: 1214-21, PMID.

Needleman P, Turk J, Jakschik BA, Morrison AR, Lefkowith JB. Arachidonic acid metabolism. Annu Rev Biochem. 1986; 55: 69-102, CrossRef.

Reshamwala SM, Patil ND. Biochemical changes in erythrocyte membrane in uncontrolled type 2 diabetes mellitus. Indian J Biochem Biophys. 2005; 42: 250-3, PMID.

Marini M, Abruzzo PM, Bolotta A, Veicsteinas A, Ferreri C. Aerobic training affects fatty acid composition of erythrocyte membranes. Lipids Health Dis. 2011; 10: 188-92, CrossRef.

Maturu P, Varadacharyulu N. Adaptive changes in fatty acid profile of erythrocyte membrane in relation to plasma and red cell metabolic changes in chronic alcoholic men. Hum Exp Toxicol. 2012; 31: 652-61, CrossRef.

Sepulveda JL, Tanhehco YC, Frey M, Guo L, Cropcho LJ, Gibson KM, et al. Variation in human erythrocyte membrane unsaturated Fatty acids: correlation with cardiovascular disease. Arch Pathol Lab Med. 2010; 134: 73-80, CrossRef.

Ozkan Y, Yilmaz OK, Ihsan AO, Yasemin E. Effects of triple antioxidant combination (vitamin E, vitamin C and a-lipoic acid) with insulin on lipid and cholesterol levels and fatty acid composition of brain tissue in experimental diabetic and non-diabetic rats. Cell Biol Int. 2005; 29: 754-60, CrossRef.

Bassi A, Avogaro A, Crepaldi C, Zambon S, Marin R, Macdonald I, et al. Short-term diabetic ketosis alters n-6 polyunsaturated fatty acid content in plasma phospholipids. J Clin Endocrinol Metab. 1996; 81: 1650-3, CrossRef.

Evstigneeva RP, Volkov I, Chudinova V. Vitamin E as a universal antioxidant and stabilizer of biological membranes. Membr Cell Biol. 1998; 12: 151-72, PMID.


Copyright (c) 2019 The Prodia Education and Research Institute

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.


Indexed by:






The Prodia Education and Research Institute