Protective Role Of Folic Acid Research Articles

Dietary folic acid intake differentially affects methionine metabolism markers and hippoccampus morphology in aged rats

Folic acid (FA) is an emerging nutritional factor in the pathogenesis of diverse neurodegenerative disorders by still unknown mechanisms. The hippocampus is altered during the loss of cognitive abilities in humans and selectively affected when homocysteine increases. The aim was to evaluate the potential protective role of folic acid in the maintenance of biochemical markers related to the methionine cycle, as well as the integrity of the hippocampus as part of the brain in aged rats. Male Sprague-Dawley rats (18 months old) were assigned to four different folic acid groups (0 mg FA/kg diet, deficient; 2 mg FA/kg diet, control; 8 mg FA/kg diet, moderate supplementation; 40 mg FA/kg diet, extra supplementation) for 30 days. We evaluated several parameters related to the methionine cycle. In addition, hippocampus areas were immunostained for specific neuronal markers and astrocytes. Serum folate levels increased according to FA dietary level (p < 0.01). There was a significant increase in the serum homocysteine concentrations in the folic acid-deficient diet group (p < 0.01). However, brain S-adenosylmethionine and S-adenosylhomocysteine did not differ significantly between the folic acid groups. Consequently, the methylation ratio was also unchanged. The morphometric analysis did not show any differences in the number of neurons and astrocytes between groups, except when comparing the folic acid-deficient diet versus folic acid-supplemented diet in the striatum of the hippocampus. Clearly, the dietary FA deficiency negatively affects the methionine metabolism biomarkers, while excessive supplementation seems to be unnecessary for optimal maintenance of the methylation cycle and hippocampus integrity.

Folate production using Lactococcus lactis ssp cremoris with implications for fortification of skim milk and fruit juices

The recent findings on the protective role of folic acid in the reduction of neural tube defects, coronary heart diseases and cancer have renewed the research on folate supplementation to combat its deficiency. Humans are auxotropic for folate synthesis, which makes them dependent on the exogenous supply of folate. Milk and fermented dairy products represent a good source of natural folate and folate binding proteins, which improve the bioavailability and stability of folate. Effective manipulation of medium additives and cultivation conditions enhanced the folate level (164 ng/ml, deconjugated folate) in skim milk by Lactococcus lactis ssp cremoris, an isolate from raw cow’s milk. The study on the factors influencing scale up of folate production in 600 ml and 5 L bioreactors displayed the importance of anoxygenic conditions on growth and stability of folate. A maximum titer of 187 ng/ml deconjugated folate was obtained in 5 L bioreactor. L. lactis also proved to be an excellent source for the enrichment of the folate content in cucumber and water melon juice.

The effects of valproic acid on renal corpuscle of pregnant rats and protective role of folic acid and vitamin E

We aimed to investigate the potential harmful effects of valproic acid (VPA), a widely used anticonvulsant in child delivery, and the protective effects of vitamin E (Vit E) and folic acid (FA) on kidney. Sodium valproate (400 mg/kg), folic acid (400 mg/kg) and vitamin E (250 mg/kg) were administered to rats on each of gestation days, 8 th , 9 th , and 10 th . The rats were sacrificed on the 20 th day of pregnancy. With thin sections of kidney biopsies, they were stained with uranyl acetate-lead citrate and examined under transmission electron microscope. The animals were divided into four groups randomly: control, VPA, VPA+FA and VPA+Vit E groups. In each group, drug procedure, surgical procedure and histological methods were performed. The histopathological findings of control group was normal. In VPA group, it showed degenerative changes especially in renal glomerular basal membrane and foot process. Both VPA+FA and VPA+Vit E groups exhibited similar ultrastructural changes and had almost the normal structure. Administration of single doses of SV (400 mg/kg) resulted in degenerative changes on kidney at ultrastructural level. Administration of FA and Vit E had a protective effect by preventing the degenerative changes to a certain degree. The aim of the present study is to examine histopathologic changes which may occur in a high risk experimental model after the administration of valproic acid. In addition, protective roles of the administration of folic acid and vitamin E are assessed.

Biochemical Study on the Protective Role of Folic Acid in Rabbits Treated with Chromium (VI)

Deleterious effects of chromium (VI) compounds are diversified affecting almost all the organ systems in a wide variety of animals. Therefore, the present study was carried out to determine the effectiveness of folic acid (FA) in alleviating the toxicity of chromium (VI) on certain biochemical parameters, lipid peroxidation, and enzyme activities of male New Zealand white rabbits. Six rabbits per group were assigned to one of four treatment groups: 0 mg FA and 0 mg Cr(VI)/kg BW (control); 8.3 μg FA/kg BW; 5 mg Cr(VI)/kg BW; 5 mg Cr(VI) plus 8.3 μg FA/kg BW, respectively. Rabbits were orally administered their respective doses every day for 10 weeks. Results obtained showed that Cr(VI) significantly (P < 0.05) increased the levels of free radicals and the activity of glutathione S-transferase (GST), and decreased the content of sulfhydryl groups (SH groups) in liver, testes, brain, kidney, and lung. The activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AlP), acid phosphatase (AcP), and lactate dehydrogenase (LDH) were significantly decreased in liver and testes due to Cr(VI) administration. Also, AlP and AcP activities were significantly decreased in kidney and lung. The activity of acetylcholinesterase (AChE) was significantly decreased in brain and plasma. Contrariwise, the activities of AST and ALT were significantly increased in plasma, while AlP and AcP decreased. Chromium (VI) treatment caused a significant decrease in plasma total protein (TP) and globulin, and increased total lipids (TL), cholesterol, glucose, urea, creatinine, and bilirubin concentrations. Folic acid alone significantly decreased the levels of free radicals in liver, brain, and kidney, and increased the content of SH-group. The activities of AST, ALT, and LDH in liver; AST, ALT, AlP, AcP, and LDH in testes; AcP in kidney; AlP and AcP in lung, and LDH in brain were significantly increased. Plasma TP and albumin were increased, while urea and creatinine were decreased. The presence of FA with Cr(VI) restored the changes in enzyme activities and biochemical parameters. In conclusion, folic acid could be effective in the protection of chromium-induced toxicity.

Effect of folic acid on homocysteine-induced trophoblast apoptosis.

In trophoblast cells exposed to homocysteine (Hcy) we observed cellular apoptosis and the inhibition of trophoblast functions. Because folate and Hcy, linked in the same metabolic pathway, are inversely related, we investigated the role of folic acid in reversing the Hcy effect in human placenta. In primary trophoblast cells we examined the cytosolic release of cytochrome c, both M30 and terminal deoxynucleotidyl transferase-mediated dUDP nick-end labelling (TUNEL) and DNA laddering. Hcy (20 micromol/l) treatment resulted in cytochrome c release from mitochondria to the cytosol, and an increased number of M30-positive trophoblast cells and TUNEL positive nuclei. Furthermore, DNA cleavage in agarose gel and the determination of histone-associated DNA fragments have been investigated. Homocysteine induced DNA fragmentation and significantly reduced hCG secretion. The addition of folic acid (20 nmol/l) resulted in inhibition of the effects of Hcy on human trophoblast. These results suggest a protective role of folic acid in the prevention of trophoblast apoptosis linked to Hcy.

Aging

Recent investigations have demonstrated a protective role for folic acid in dysplasia and neoplasia, through an unknown mechanism. The current study was designed to evaluate whether the protective role of folic acid is due, in part, to its antiproliferative properties. In addition, because colorectal neoplasia is more common with increasing age, we have compared results in both old (22 months) and young (3 months) rats. Colorectal mucosal explants of rats treated with the known carcinogen methylazoxymethanol, were supplemented with folic acid. Ornithine decarboxylase was then measured as an index of cellular proliferative activity. We observed that supplemental folic acid suppressed carcinogen-induced ornithine decarboxylase activity by 64% in the old and 74% in the young rats. Furthermore, a similar phenomenon was observed for tyrosine kinase, which was measured for comparison. The suppression of hyperproliferative activity by supplemental folic acid may contribute to the protective effect of folic acid in colorectal neoplasia.