Folic Acid Supplementation Can Reduce the Endothelial Damage in Rat Brain Microvasculature Due to Hyperhomocysteinemia,

Abstract

To evaluate the effects of dietary folic acid supplementation on the cerebral vascular damage induced by hyperhomocysteinemia, rats were fed a diet containing 3.0 g/kg homocystine for 2 wk and then either 3.0 g/kg homocystine or 3.0 g/kg homocystine plus 0.008 g/kg folic acid for 8 wk. Control rats consumed the AIN-93 Maintenance diet throughout the experiment. The cerebral expression of glucose transporter-1 was measured by Western blot analysis and cerebrovascular structural alterations were evaluated by electron microscopy. The homocystine diet significantly increased the plasma levels of homocysteine and TBARS and decreased the cerebral expression of glucose transporter-1 (GLUT-1) with a concomitant increase in the percentage of damaged cerebral vessels. The inclusion of dietary folic acid for 8 wk caused plasma homocysteine levels to be the same as in control rats and it significantly upregulated the cerebral expression of GLUT-1 that was significantly reduced by hyperhomocysteinemia. Folic acid supplementation also significantly decreased the incidence of damaged vessels due to hyperhomocysteinemia. These results and the electron microscopy findings suggested that folic acid supplementation might reduce the detrimental effects on the endothelium caused by experimentally induced hyperhomocysteinemia.

Effect of folate deficiency on placental DNA methylation in hyperhomocysteinemic rats

“…The folate levels were lower in HFD group than in HFS group in both the liver and placenta. These results are in good agreement with our previous report [15] that dietary homocystine supplementation caused hyperhomocysteinemia and that folate supplementation in a homocystinesupplemented status caused an increase in hepatic SAM/ SAH ratio in adult male rats. DNA methylation is known to be altered by several factors, including changes in the concentrations of SAM and SAH [20,21].…”

“…Thirty-six animals were divided into the following three dietary groups: folate-supplemented (FS; 8 mg/kg folic acid, n=12), homocystine-and folate-supplemented (HFS; 3 g/kg homocystine and 8 mg/kg folic acid, n=12) and homocystine-supplemented and folate-deficient (HFD; 3 g/ kg homocystine and no folic acid, n=12). The diets used are detailed elsewhere [15]. Female Sprague-Dawley rats (Orient Company, Seoul, Korea) were fed the experimental diets beginning at 5 weeks of age.…”

Tratamento dietético da hiper-homocisteinemia na doença arterial periférica

“…As lesões endoteliais encontradas nos ratos hiper-homocisteinêmicos eram semelhantes às lesões tipicamente encontradas em doenças cerebrais degenerativas como Alzheimer e Parkinson. Em contrapartida, a inclusão de doses moderadas de ácido fólico na dieta por 8 semanas resultou em mudanças morfológicas e, consequentemente, reduziu significantemente essas lesões endoteliais 76 . Em 250 pacientes submetidos a angioplastia coronariana, a terapia combinada de ácido fólico (1.000 mg), vitamina B12 (400 mg) e B6 (10 mg), utilizada por 6 meses, pôde ser utilizada como terapia adjuvante na angioplastia coronariana, pois promoveu redução significante da homocisteinemia e da taxa de reestenose pós-angioplastia 77 .…”

Short-Term Hyperhomocysteinemia-Induced Oxidative Stress Activates Retinal Glial Cells and Increases Vascular Endothelial Growth Factor Expression in Rat Retina

“…18,19) Several studies have focused on exploration of retinal injury prevention strategies through food substances with antioxidant properties 8) or nutrients such as B vitamins. 4) For this, the development of a proper animal model for retinal injury should be quite useful.…”

“…The remaining 16 rats were allocated to either the control group (group C, n ¼ 8), which was fed the AIN-93 maintenance diet, 20) or the experimental group (group H, n ¼ 8), which was fed a diet that contained 3.0 g/kg homocysteine and no folic acid for 2 weeks, as described previously. 19) All the rats were allowed free access to food and water.…”