EFFICACY OF COSUPPLEMENTATION THERAPY WITH VITAMINS B9, B12, AND D ON ENDOTHELIAL DYSFUNCTION IN STREPTOZOTOCIN-INDUCED DIABETIC RATS
DOI:
https://doi.org/10.22159/ajpcr.2018.v11i9.25361Keywords:
Endothelial dysfunction, Diabetes, Vitamin D, Folic acid, Vitamin B12Abstract
Objective: This study evaluated the effects of Vitamins D, B9, and B12 given individually or combined in ameliorating some biochemical parameters related to endothelial dysfunction in diabetic rats.
Methods: A total of 50 Sprague-Dawley male rats were divided into five groups: Control, diabetic, diabetic received Vitamin D, diabetic received Vitamins B9 and B12, and diabetic received Vitamins B9, B12, and D. At the end of 6 weeks, the rats were sacrificed and a set of assays was carried out to determine: Fasting blood sugar (FBS), lipid profile, nitric oxide (NO), homocysteine (Hcy), malondialdehyde (MDA), and serum levels of Vitamins B9, B12, and D.
Results: Diabetic rat received Vitamin D and diabetic rat received Vitamins B9 and B12 had a significant decline in the levels of FBS, lipid profile, and Hcy with reduced MDA (p<0.05) release but significant increase in NO level. On the same hand, diabetic rat received combined supplementation of Vitamins B9, B12, and D had more pronounced effect (p<0.00).
Conclusion: Given these findings, the combined vitamins therapy had antiatherosclerotic effects by inhibiting lipid peroxidation and stimulating NO production, resulting in amelioration the endothelial dysfunction in diabetic rat.
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Hamilton SJ, Watts GF. Endothelial dysfunction in diabetes: Pathogenesis, significance, and treatment. Rev Diabet Stud 2013;10:133-56.
Sena CM, Pereira AM, Seiça R. Endothelial dysfunction - a major mediator of diabetic vascular disease. Biochim Biophys Acta 2013;1832:2216-31.
Wang Z, Li AY, Guo QH, Zhang JP, An Q, Guo YJ, et al. Effects of cyclic intermittent hypoxia on ET-1 responsiveness and endothelial dysfunction of pulmonary arteries in rats. PLoS One 2013;8:e58078.
Boucher BJ. Vitamin D insufficiency and diabetes risks. Curr Drug Targets 2011;12:61-87.
Molinari C, Uberti F, Grossini E, Vacca G, Carda S, Invernizzi M, et al 1α,25-dihydroxycholecalciferol induces nitric oxide production in cultured endothelial cells. Cell Physiol Biochem 2011;27:661-8.
Polidoro L, Properzi G, Marampon F, Gravina GL, Festuccia C, Di Cesare E, et al. Vitamin D protects human endothelial cells from H2O2 oxidant injury through the mek/Erk-sirt1 axis activation. J Cardiovasc Transl Res 2013;6:221-31.
Uberti F, Lattuada D, Morsanuto V, Nava U, Bolis G, Vacca G, et al. Vitamin D protects human endothelial cells from oxidative stress through the autophagic and survival pathways. J Clin Endocrinol Metab 2014;99:1367-74.
Hussein J, El-Khayat Z, Morsy S, Oraby F, Singer G. The effect of fish oil on oxidant/antioxidant status in diabetic rats through the reduction of arachidonic acid in the cell membrane. Int J Pharm Pharm Sci 2014;6 Suppl 2:196-9.
Bulynko YA, O’Malley BW. Nuclear receptor coactivators: Structural and functional biochemistry. Biochemistry 2011;50:313-28.
Prosser DE, Jones G. Enzymes involved in the activation and inactivation of vitamin D. Trends Biochem Sci 2004;29:664-73.
Bikle DD. Extra renal synthesis of 1,25 dihydroxy vitamin D and its health implications. Clin Rev Bone Miner Metab 2009;7:114-25.
Hussein J, EL-Khayat Z, Moify M. Study of arachidonic acid releasing status in diabetic rats treated with flaxseed oil. Int J Pharm Pharm Sci 2016;8:975-1491.
Kohli R, Meininger CJ, Haynes TE, Yan W, Self JT, Wu G, et al. Dietary L-arginine supplementation enhances endothelial nitric oxide synthesis in streptozotocin-induced diabetic rats. J Nutr 2004;134:600-8.
Koleganova N, Piecha G, Ritz E, Gross ML. Calcitriol ameliorates capillary deficit and fibrosis of the heart in subtotally nephrectomized rats. Nephrol Dial Transplant 2009;24:778-87.
Deniz ÖG, Kıvrak EG, Kaplan AA, Altunkaynak BZ. Effects of folic acid on rat kidney exposed to 900 MHz electromagnetic radiation. J Microsc Ultrastruct 2017;5:198-205.
Ekaidem IS, Akpanabiatu MI, Uboh FE, Eka OU. Effect of folic acid and vitamin B(12) administration on phenytoin induced toxicity in rats. Indian J Clin Biochem 2007;22:36-40.
Passing H, Bablok. A new biometrical procedure for testing the equality of measurements from two different analytical methods. Application of linear regression procedures for method comparison studies in clinical chemistry, part I. J Clin Chem Clin Biochem 1983;21:709-20.
Allain CC, Poon LS, Chan CS, Richmond W, Fu PC. Enzymatic determination of total serum cholesterol. Clin Chem 1974;20:470-5.
Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972;18:499-502.
Glick MR, Ryder KW, Jackson SA. Graphical comparisons of interferences in clinical chemistry instrumentation. Clin Chem 1986;32:470-5.
Hussein J, El-Khayat Z, Abdel Latif Y, Medhat D, Morsy S, Oraby F. Evaluation of brain monoamines in diabetic rats treated with quercetin. J Chem Pharm Res 2014;6:384-90.
Tatsch E, Bochi GV, Pereira Rda S, Kober H, Agertt VA, de Campos MM, et al. A simple and inexpensive automated technique for measurement of serum nitrite/nitrate. Clin Biochem 2011;44:348-50.
Ruiz-Larrea MB, Leal AM, Liza M, Lacort M, de Groot H. Antioxidant effects of estradiol and 2-hydroxyestradiol on iron-induced lipid peroxidation of rat liver microsomes. Steroids 1994;59:383-8.
Mitri J, Pittas AG. Vitamin D and diabetes. Endocrinol Metab Clin North Am 2014;43:205-32.
Sinclair KD, Allegrucci C, Singh R, Gardner DS, Sebastian S, Bispham J, et al. DNA methylation, insulin resistance, and blood pressure in offspring determined by maternal periconceptional B vitamin and methionine status. Proc Natl Acad Sci U S A 2007;104:19351-6.
Mertens PR, Muller RM. Vitamin D and cardiovascular risk. Int Urol Nephrol 2010;42:165-71.
Malek HA, Shata A. Effect of a high dose of vitamin D on a rabbit model of atherosclerosis. Int J Immunopathol Pharmacol 2014;27:195-201.
Antoniades C, Antonopoulos AS, Tousoulis D, Marinou K, Stefanadis C. Homocysteine and coronary atherosclerosis: From folate fortification to the recent clinical trials. Eur Heart J 2009;30:6-15.
Bhargava S, Ali A, Bhargava EK, Manocha A, Kankra M, Das S, et al. Lowering homocysteine and modifying nutritional status with folic acid and vitamin B(12) in indian patients of vascular disease. J Clin Biochem Nutr 2012;50:222-6.
Hoffman M. Hypothesis: Hyperhomocysteinemia is an indicator of oxidant stress. Med Hypotheses 2011;77:1088-93.
Arzamastsev DD, Karpenko AA, Kostiuchenko GI. Inflammation of the vascular wall and hyperhomocysteinemia in patients with atherosclerosis obliterans of lower limb arteries. Angiol Sosud Khir 2012;18:27-30.
Magné J, Huneau JF, Borderie D, Mathé V, Bos C, Mariotti F, et al. Plasma asymmetric and symmetric dimethylarginine in a rat model of endothelial dysfunction induced by acute hyperhomocysteinemia. Amino Acids 2015;47:1975-82.
Emeksiz HC, Serdaroglu A, Biberoglu G, Gulbahar O, Arhan E, Cansu A, et al. Assessment of atherosclerosis risk due to the homocysteine-asymmetric dimethylarginine-nitric oxide cascade in children taking antiepileptic drugs. Seizure 2013;22:124-7.
Ellam T, Hameed A, ul Haque R, Muthana M, Wilkie M, Francis SE, et al. Vitamin D deficiency and exogenous vitamin D excess similarly increase diffuse atherosclerotic calcification in apolipoprotein E knockout mice. PLoS One 2014;9:e88767.
Kriebitzsch C, Verlinden L, Eelen G, van Schoor NM, Swart K, Lips P, et al 1,25-dihydroxyvitamin D3 influences cellular homocysteine levels in murine preosteoblastic MC3T3-E1 cells by direct regulation of cystathionine β-synthase. J Bone Miner Res 2011;26:2991-3000.
Nursalim A, Siregar P, Widyahening IS. Effect of folic acid, vitamin B6 and vitamin B12 supplementation on mortality and cardiovascular complication among patients with chronic kidney disease: An evidence-based case report. Acta Med Indones 2013;45:150-6.
Caruso R, Campolo J, Sedda V, De Chiara B, Dellanoce C, Baudo F, et al. Effect of homocysteine lowering by 5-methyltetrahydrofolate on redox status in hyperhomocysteinemia. J Cardiovasc Pharmacol 2006;47:549-55.
Stanhewicz AE, Kenney WL. Role of folic acid in nitric oxide bioavailability and vascular endothelial function. Nutr Rev 2017;75:61-70
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