Thiamine pyrophosphate diminishes nitric oxide synthesis in endothelial cells
Abstract
Abstract. Although thiamine pyrophosphate (TPP) is considered a protective agent for endothelial cells, it is still unknown if this is associated with nitric oxide (NO) synthesis. Our aim was to evaluate the synthesis of NO in endothelial cells incubated with TPP and high glucose concentrations. Endothelial cells from the umbilical cord vein from newborns (n = 20), were incubated with 5, 15 or 30 mmol/L glucose, in absence or presence of 0.625 mg/ml of TPP. Our results showed a significant increase in cell proliferation (> 40%; P < 0.05), and cell viability (> 90%; P < 0.001) after 48 h in endothelial cells cultured with glucose plus TPP. Likewise, in the presence of glucose and TPP an important rise in the consumption of glucose by the endothelial cells was observed after 24 h (> 7%; P < 0.001) and 48 h (> 10%; P < 0.05). Additionally, the levels of lactate after incubation with glucose and TPP showed only slight variations after 48 h (P < 0.05). However, these changes were clearly different from those observed in the absence of TPP. Interestingly, we found that the changes mentioned were linked with reduced levels of nitrites both at 24 h (< 171 pmol/μg protein; P < 0.001), and 48 h (< 250 pmol/μg protein; P < 0.05), which was associated with a reduced expression of mRNA of eNOS in endothelial cells incubated with TPP and high glucose. In conclusion, the presence of TPP regulates the consumption of glucose and the synthesis of NO, which would explain its protective effect in the endothelium of diabetic patients.
References
1 . Geneeskundig Tijdschrift Voor Nederlandsch-Indie. The isolation of the anti beri beri vitamin. Nutr Rev. 1982;40(2):53–4.
2 . Thiamine in Clinical Practice. JPEN J Parenter Enteral Nutr. 2015;39(5):503–20.
3 Role of Thiamine in Health and Disease. Nutr Clin Pract. 2019;34(4):558–64.
4 . Structure, mechanism and catalytic duality of thiamine-dependent enzymes. Cell Mol Life Sci. 2007;64(7–8):892–905.
5 . Effects of thiamine and benfotiamine on intracellular glucose metabolism and relevance in the prevention of diabetic complications. Acta Diabetol. 2008;45(3):131–41.
6 . Blood thiamine levels in outpatients with diabetes mellitus. J Nutr Sci Vitaminol (Tokyo). 1987;33(6):421–30.
7 . Thiamine status in patients undergoing lower extremity amputation due to diabetic foot lesion. Int J Vitam Nutr Res. 2012;82(6):369–73.
8 . Metabolic benefits of six-month thiamine supplementation in patients with and without diabetes mellitus type 2. Clin Med Insights Endocrinol Diabetes. 2014;7:1–6.
9 . Effect of intravenous infusions of thiamine on the disposition kinetics of thiamine and its pyrophosphate. J Clin Pharm Ther. 2003;28(1):47–51.
10 . Comparative effects of vitamin K2 and estradiol on experimental arteriosclerosis with diabetes mellitus. Int J Vitam Nutr Res. 2000;70(6):301–04.
11 . Diabetes mellitus and vascular endothelial dysfunction: current perspectives. Curr Vasc Pharmacol. 2012;10(1):19–32.
12 . Hypo- and hyperglycemia impair endothelial cell actin alignment and nitric oxide synthase activation in response to shear stress. PLoS One. 2013;8(6):e66176.
13 Thiamine corrects delayed replication and decreases production of lactate and advanced glycation end-products in bovine retinal and human umbilical vein endothelial cells cultured under high glucose conditions. Diabetologia. 1996;39(11):1263–68.
14 Thiamine reverses hyperglycemia-induced dysfunction in cultured endothelial cells. Surgery. 2001;130(5):851–58.
15 . Thiamine deficiency leads to reduced nitric oxide production and vascular dysfunction in rats. Nutr Metab Cardiovasc Dis. 2014;24(2):183–88.
16 . Could thiamine pyrophosphate be a regulator of the nitric oxide synthesis in the endothelial cell of diabetic patients? Med Hypotheses. 2011;76(5):629–31.
17 Effect of thiamine pyrophosphate on retinopathy induced by hyperglycemia in rats: A biochemical and pathological evaluation. Indian J Ophthalmol. 2016;64(6):434–39.
18 The Protective Effect of Thiamine Pryophosphate Against Sugar-Induced Retinal Neovascularisation in Rats. Int J Vitam Nutr Res. 2018;88(3–4):137–43.
19 . DNA damage during glycation of lysine by methylglyoxal: assessment of vitamins in preventing damage. Amino Acids. 2007;33(4):615–21.
20 HUVECs from newborns with a strong family history of diabetes show diminished ROS synthesis in the presence of high glucose concentrations. Diabetes Metab Res Rev. 2007;23(1):71–80.
21 . Reduced NO synthesis and eNOS mRNA expression in endothelial cells from newborns with a strong family history of type 2 diabetes. Diabetes Metab Res Rev. 2007;23(7):559–66.
22 . Metabolic and permeability changes caused by thiamine deficiency in immortalized rat brain microvessel endothelial cells. Brain Res. 1997;756(1–2):133–40.
23 . High glucose-induced apoptosis in human coronary artery endothelial cells involves up-regulation of death receptors. Cardiovasc Diabetol. 2011;10:73.
24 . Mitochondrial function and toxicity: role of B vitamins on the one-carbon transfer pathways. Chem Biol Interact. 2006;163(1–2):113–32.
25 . Thiamine deficiency in diabetes mellitus and the impact of thiamine replacement on glucose metabolism and vascular disease. Int J Clin Pract. 2011;65(6):684–90.
26 . Lactic acidosis in thiamine deficiency. Clin Nutr. 1993;12(2):108–11.
27 Rapid reversal of severe lactic acidosis after thiamine administration in critically ill adults: a report of 3 cases. Nutr Clin Pract. 2015;30(1):104–10.
28 Hyperglycaemia enhances nitric oxide production in diabetes: a study from South Indian patients. PLoS One. 2015;10(4):e0125270.
29 . Regulation of intracellular glucose and polyol pathway by thiamine and benfotiamine in vascular cells cultured in high glucose. J Biol Chem. 2006;281(14):9307–13.
30 . Barja-Fidalgo C, de Freitas MS. Expression of inducible nitric oxide synthase in human umbilical vein endothelial cells during primary culture. Nitric Oxide. 2002;7(4):254–61.