Protective Effect Of Folic Acid Research Articles

Protective effects of folic acid on oxidative damage of rat spleen induced by lead acetate

Lead (Pb) is a heavy metal environmental pollutant that can cause functional damage and anemia of immune organs. More and more evidence indicate that the toxicity of lead was related to apoptosis driven by oxidative stress and endoplasmic reticulum stress. This article mainly discusses the protective effect and mechanism of folic acid intervention on lead-induced spleen injury and apoptosis. In this study, Sprague-Dawley rats were randomly divided into control group, lead exposure group (0.2% lead acetate), folic acid + lead group (0.4 mg/kg folic acid and 0.2% lead acetate), and folic acid group (0.4 mg/kg folic acid). By recording and calculating the rat's initial body weight, final body weight, net weight gain, daily weight gain, and spleen index, observe the rat's weight change and spleen weight. And adopt the immunofluorescence staining method to determine the expression level of NrF2, HO-1, GRP78, CHOP protein in the spleen. The results showed that The 0.4 mg/kg folic acid diet did not significantly improve in the body weight and spleen index of lead-exposed rats (P > 0.05). While compared with the control group, the expression levels of HO-1 and CHOP protein were significantly increased in the lead exposure group (P < 0.05), and the expression levels of HO-1 and CHOP protein were significantly reduced in the folic acid intervention group (P < 0.05). In conclusion, lead exposure increased the expression levels of HO-1 and CHOP in the spleen of rats, and caused damage to the spleen. Folic acid down-regulated the expression levels of HO-1 and CHOP proteins through the two pathways of NrF2/HO-1 and GRP78/CHOP, thereby exerting a certain protective effect and alleviating the spleen caused by lead-induced oxidative stress and endoplasmic reticulum stress damage.

The effect of folate on ischemia/reperfusion injury in a rat adnexal torsion model.

The ischemia/reperfusion (I/R) injury of ovaries in adnexal torsion may have inadvertent consequences. Many agents have been studied in terms of their ability to prevent reperfusion damage to ovaries in suspected cases. In this study, folic acid, known to have antioxidative properties, was investigated to determine whether it played a role in the prevention of I/R damage in a rat ovarian torsion model. In this experimental study, 40 female adult Wistar-Albino rats were randomly divided into five groups as control, ischemia, I/R, Fol2 (2mg/kg folic acid), and Fol4 (4mg/kg folic acid). In the Fol2 and Fol4 groups, folic acid was intraperitonelly administered 30min before reperfusion. Blood samples were obtained from the tails of each rat at the second hour of reperfusion. The total oxidant status (TOS), total antioxidant status, cystatin C and folic acid levels of the five groups were investigated. Folic acid in 2mg/kg dose could moderately increase the serum folic acid concentration (15.75-19.95ng/ml, p < 0.05), reduce the level of cystatin C (0.18-0.12μg/L, p < 0.05), and had a tendency to improve the oxidative stress injury (OSI: 76.05-33.06, p > 0.05), although there was no statistical difference in TOS levels (p = 0.07). Folic acid in 4mg/kg dose, could significantly increase the serum folic acid concentration (15.75-37.65ng/ml). However, it did not significantly reduce the level of cystatin C (0.18-0.19μg/L, p > 0.05), and did not improve oxidative stress injury (76.05-130.58, p > 0.05). Folic acid in 2mg/kg dose might improve the ovarian I/R injury though this was not statistically significant. Further studies are required to reach a definitive conclusion about the protective effect of folic acid in I/R injury.

Arsenic suppresses GDF1 expression via ROS-dependent downregulation of specificity protein 1.

Inorganic arsenic, an environmental contaminant, has adverse health outcomes. Our previous studies showed that arsenic causes abnormal cardiac development in zebrafish embryos by downregulating Dvr1/GDF1 expression and that folic acid protects against these effects. However, the mechanism by which arsenic represses Dvr1/GDF1 expression remains unknown. Herein, we demonstrate that specificity protein 1 (Sp1) acts as a transcriptional activator of GDF1. Arsenic treatment downregulated Sp1 at both the mRNA and protein level and its downstream targets GDF1 and SIRT1. Chromatin immunoprecipitation analysis showed that the occupancy of Sp1 on the GDF1 or SIRT1 promoter was significantly reduced in response to arsenite. Further investigation showed that Sp1 overexpression inhibited the arsenic-mediated decrease in GDF1 and SIRT1, while Sp1 knockdown had the opposite effect. We found that expression of the oxidative adaptor p66shc was inversely related to that of SIRT1 and that the binding of SIRT1 to the p66shc promoter was sharply attenuated by arsenite treatment. SIRT1 overexpression attenuated p66shc expression but enhanced GDF1 protein expression, while SIRT1 depletion exerted the opposite effect. Both the antioxidants N-acetylcysteine and folic acid reversed the arsenic-mediated repression of Sp1, GDF1 and SIRT1. Moreover, wild-type p66shc overexpression enhanced the arsenic-mediated repression of Sp1, GDF1 and SIRT1, which was accompanied by an increase in intracellular reactive oxygen species (ROS) levels, while both overexpression of a dominant negative p66shcSer36Ala mutant and deficiency in p66shc reversed these effects. Taken together, our results revealed that arsenic suppresses GDF1 expression via the ROS-dependent downregulation of the Sp1/SIRT1 axis, which forms a negative feedback loop with p66shc to regulate oxidative stress. Our findings reveal a novel molecular mechanism underlying arsenic toxicity and provide new insight into the protective effect of folic acid in arsenic-mediated toxicity.

Folic acid attenuates remodeling and dysfunction in the aging heart through the ER stress pathway

AIMsAge-related structure changes and dysfunction of heart are likely to contribute heart failure in elderly people. Recent studies have shown that folic acid supplementation effectively delays age-related declines; nevertheless, the role and mechanism of folic acid in protection against cardiac aging remain unclear. The aim of the current study was to determine whether folic acid inhibits remodeling and dysfunction during the aging process and to elucidate its underlying mechanisms. Main methodsMale C57BL/6 mice aged 4 months (adult) and 14 months (aged) were fed a standard diet or a folic acid diet for 6 months. Echocardiograms and histological evaluations were used to detect left ventricle (LV) function, LV remodeling, cardiac fibrosis, apoptosis and oxidative stress. Senescence-associated β-galactosidase activity staining was used to detect cardiac senescence rate. Western blotting was employed to detect the levels of senescence and ER stress signaling. Key findingLV hypertrophy was reduced and LV function was preserved in aged mice that consumed folic acid. LV remodeling, fibrosis, apoptosis and oxidative stress were also reduced in mice that consumed folic acid. Senescence-associated β-galactosidase activity staining revealed that folic acid attenuated cardiac senescence by down-regulating p53/p21/p16 levels. Protein assays of myocardial tissue revealed that the ER stress pathway is the important underlying mechanism during cardiac senescence. The involvement of these pathways was confirmed by doxorubicin-induced H9C2 cardiomyocyte senescence. SignificanceThese findings suggest that folic acid prevents age-related cardiac remodeling and dysfunction and attenuates cellular senescence. ER stress responses may be the mechanisms involved in the protective effect of folic acid against cardiac aging.

Periconceptional use of cod liver oil, a vitamin D source, could decrease the risk of CHD in offspring.

To explore if there is association between vitamin D supplementation through cod liver oil ingestion around the periconceptional period and the risk of developing severe CHD in offspring. Furthermore, we would examine the interaction between vitamin D and folic acid supplementation in the association. A case-control study was conducted in Shanghai Children's Medical Center, in which, a total of 262 severe CHD cases versus 262 controls were recruited through June 2016 to December 2017. All children were younger than 2 years. To reduce potential selection bias and to minimise confounding effects, propensity score matching was applied. After propensity score matching, vitamin D supplementation seemed to be associated with decreased odds ratio of severe CHD (odds ratio = 0.666; 95% confidence intervals: 0.449-0.990) in the multivariable conditional logistic analysis. Furthermore, we found an additive interaction between vitamin D and folic acid supplementation (relative excess risk due to interaction = 0.810, 95% confidence intervals: 0.386-1.235) in the association. The results suggested that maternal vitamin D supplementation could decrease the risk of offspring severe CHD; moreover, it could strengthen the protective effect of folic acid. The significance of this study lies in providing epidemiological evidence that vitamin D supplementation around the periconceptional period could be a potential nutritional intervention strategy to meet the challenge of increasing CHD.

Protective effects of folic acid on retina in diabetic mice and its anti-oxidative stress mechanism

Objective To explore the protective effects of folic acid on retinas and its anti-oxidative stress mechanism in diabetic mice. Methods Thirty-two 16-week-old SPF degree male db/db mice were randomized into model group and folic acid group, and 16 matched C57BL/KsJ mice were used as controls.Folic acid was used to the mice by oral gavage once per day with the dose of 71 μg/kg (2 ml) for 60 days in the folic acid group, and the same volume of normal saline solution was used in the model group and control group in the same way.The activities, mental state, body weight, and fasting plasma glucose (FPG) of the mice were recorded during experiment.At the end of the intervention, the mice were sacrificed and the retinas and blood sample were obtained.The histopathology of the retinas was examined with hematoxylin- eosin staining; serum homocysteine (Hcy) was detected by ELISA assay; the relative expressions of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) mRNA were detected in the retinas by real-time fluorescence quantitative PCR; the relative expressions of B lymphoma 2 protein (bcl-2), bcl-2 related X protein (bax), 3-nitrotyrosine (3-NT) and 4-Hydroxynonine (4-HNE) proteins were assayed by Western blot assay; superoxide dismutase (SOD), 8-hydroxydeoxyguanosine (8-OHdG) and malondialdehyde (MDA) levels in the retinas were detected by biochemical kits, and immunofluorescence assay was used to detect the expression of NADPH oxidation 4 (NOX4) in the retinas.The use and care of the experimental animals adhered to the ARVO Statement by the American Association for Vision and Ophthalmology Research and this study protocol was approved by Ethic Committee of Qinghai University (QHDX 2018-35). Results Over the experimental period, The FPG was normal and body weight was gradually increased in the mice of control group.The FPG>16.7 mmol/L and the mice appeared obese.In the folic acid group, both body mass and FPG of the mice were gradually reduced.At the end of drug administration, serum Hcy concentration of the mice was (27.18±3.18)μmol/L in the model group, which was significantly higher than (8.28±2.18)μmol/L in the control group and (13.73±2.54)μmol/L in the folic acid group (all at P<0.05). The retinal structure was intact in the control group, and the retinas were thinning with more capillaries and inflammatory cells in the model group, the thickness of the retinas was increased and the capillaries and inflammatory cells were decreased in the folic acid group.The relative expressions of TNF-α and IL-6 mRNA in the retinas were significantly higher in the model group than those in the control group, and those in the folic acid group were reduced in comparison with the model group (all at P<0.05). The relative expression of bcl-2 protein in the retinas of folic acid group was lower than that in the control group and higher than that in the model group, and the relative expressions of bax, 3-NT and 4-HNE proteins in the retinas of the folic acid group were significantly higher than those in the control group and lower than those in the model group (all at P<0.05 ). The T-SOD activity in the folic acid group was significantly stronger than that in the control group and weaker than that in the model group, and the concentrations of 8-OHdG and MDA in the retinas of the folic acid group were significantly reduced in comparison with those of the control group and elevated in comparison with those of the model group (all at P<0.05). The expressing intensity of NOX4 protein in the retinas of the folic acid group was significantly weaker than that of the model group. Conclusions Folic acid appears aprotective effect on retinal tissue in diabetic mice by reducing serum Hcy, inhibiting oxidative stress and cell apoptosis. Key words: Diabetes/complication; Retina; Protective effect; Folic acid; Oxidative stress; Disease model; Mice

Morphometric and Phasic Activity Changes of Urinary Bladder in Hyperthyroid Rats and the Possible Protective Effect of Folic Acid

Abstract Background: Hyperthyroidism was one of the most com-mon endocrine disorders. Urinary tract dysfunctions were common symptoms in hyperthyroid patients. Folic acid is affected by Thyroid dysfunction as hyperthyroidism is asso-ciated with subclinical deficiency and depletion of folate stores. Aim of Study: To study the morphometric and the in-vitro contractility changes of the urinary bladder in hyperthyroid rats, and the protective effect of folic acid and its possible mechanisms. Material and Methods: Forty male albino rats divided into four groups: Control, hyperthyroid, folic and (hyperthyroid + folic) groups. TSH, T3, T4, MDA & PGE2 were measured. Rats were then sacrificed. The weight, morphometric changes and phasic activity of the urinary bladder were assayed. Results: Hyperthyroid group significantly decreased TSH and increased T3 (Triiodothyronine), T4 (thyroxine), MDA (malondialdehyde) and PGE2 (prostaglandin E2), bladder weight, wall, and lumen areas with unchanged wall thickness, and increased smooth muscle and urothelium areas with unchanged collagen area and increase the contractile response of the urinary bladder strips to acetylcholine when compared to the control group. Co-administration of folic acid to hyper-thyroid rats significantly increased TSH and decreased T3, T4, MDA and PGE2, bladder weight, wall, lumen areas, smooth muscle, urothelium areas and the contractile response of the urinary bladder strips to acetylcholine when compared to the hyperthyroid group. Conclusions: Folic acid protects against enhanced bladder contractility and bladder remodeling in hyperthyroid rats possibly through ameliorating the increased thyroid hormones levels, anti-oxidative, and anti-inflammatory properties.

PM2.5-induced extensive DNA methylation changes in the heart of zebrafish embryos and the protective effect of folic acid

We previously found that folic acid (FA) attenuated cardiac defects in zebrafish embryos exposed to extractable organic matter (EOM) from PM2.5, but the underlining mechanisms remain to be elucidated. Since DNA methylation is crucial to cardiac development, we hypothesized that EOM-induced aberrant DNA methylation changes could be diminished by FA supplementation. In this study, zebrafish embryos were exposed to EOM in the absence or presence of FA. Genomic-wide DNA methylation analysis identified both DNA hypo- and hyper-methylation changes in CCGG sites in zebrafish embryos exposed to EOM, which were attenuated by FA supplementation. We identified a total of 316 genes with extensive DNA methylation changes in EOM samples but little or no DNA methylation changes in EOM plus FA samples. The genes were involved in critical cellular processes and signaling pathways important for embryo development. In addition, the EOM-decreased SAM/SAH ratio was counteracted by FA supplementation. Furthermore, FA attenuated the EOM-induced changes in the expression of genes involved in the regulation of DNA methylation and in folate biosynthesis. In conclusion, our data suggest that FA supplementation protected zebrafish embryos from the cardiac developmental toxicity of PM2.5 by alleviating EOM-induced DNA methylation changes.

Valproic acid effect on neural tube defects is not prevented by concomitant folic acid supplementation: Early chick embryo model pilot study

BackgroundNeural tube defect is one of the most prevalent congenital malformations and it involves a variety of malformations ranging from anencephaly to spina bifida. Folic acid supplementation during pregnancy is known to reduce risk of neural tube defects. Antiepileptic drugs have been associated with neural tube defects, one of which is valproic acid. Protective effect of folic acid on congenital malformations in patients using valproic acid or other antiepileptic medicines during pregnancy has not clearly been delineated uniformly in previous clinical series. In this experimental animal study of early chick embryo model, we would like to determine if there is any dose-response relationship between VA and NTDs and if there is any protective effect of FA on this relationship in early chick embryo period. MethodsOne hundred twenty-two fertile leghorn type chicken eggs were used in this study. Six groups, each of which composed of 20 fertilized eggs, were categorized as: group A-control, group B- folic acid, group C-low-dose valproic acid, group D-high-dose valproic acid, group E-low-dose valproic acid + folic acid, group F-high-dose valproic acid + folic acid. Eggs were hatched for 24 h and injected with destined solutions and hatched till 72th hour. ResultsNo neural tube defect was observed in group A and B. High dose valproic acid led to significantly higher number of embryos with neural tube defects compared to low-dose valproic acid (p = 0.018). This significant difference was also present between low-dose and high dose valproic acid combined with folic acid (p = 0.031). When effect of folic acid was evaluated no significant difference observed between groups. ConclusionsEven though number of embryos with neural tube defects decreased with concomitant folic acid administration, this difference could not reach a statistical level. More experimental animal and large-scaled prospective clinical studies are in need to detect folic acid mechanism in inhibiting antiepileptic drugs, if any present.

Protective effect of folic acid on vulnerability to oxidative stress in dental pulp stem cells of deciduous teeth from children with orofacial clefts

Orofacial clefts (OFCs) are among the most common congenital craniofacial malformations, including cleft lip with or without cleft palate as the core symptoms. Developmental or functional defects in neural crest cells (NCCs) that contribute to craniofacial morphogenesis are involved in OFC development. Previous studies have suggested that oxidative stress in NCCs is involved in the development of OFCs, suggesting that the anti-oxidative activity of folic acid (FA) could have protective effects. However, studies of human-derived NCCs are limited, as these cells are predominantly active during the embryonic stage. In this study, the effects of oxidative stress and FA were evaluated in human OFCs. In particular, NCC-derived stem cells from human exfoliated deciduous teeth (SHEDs) were obtained from 3 children with non-syndromic cleft lip with cleft palate (CLPs) and from 3 healthy children (CTRLs). Mitochondrial reactive oxygen species (ROS) levels were significantly higher in CLPs than in CTRLs and were associated with lower mRNA expression levels of superoxide dismutase 1 (SOD1) and decreased cell mobility. In addition, significantly greater vulnerability to pyocyanin-induced ROS, mimicking exogenous ROS, was observed in CLPs than in CTRLs. These vulnerabilities to endogenous and exogenous ROS in CLPs were significantly improved by FA. These results indicated that the transcriptional dysregulation of SOD1 in NCCs is an oxidative stress-related pathological factor in OFCs, providing novel evidence for the benefits of perinatal anti-oxidant supplementation, including FA, for the management of these common deformities.

Postnatal Administration of Homocysteine Induces Cerebellar Damage in Rats: Protective Effect of Folic Acid

A widely held view suggests that homocysteine (Hcy) can contribute to neurodegeneration through promotion of oxidative stress. There is evidence that homocysteine is toxic to cerebellar Purkinje neurons in vitro; however, in vivo action of Hcy on Purkinje cell has not been investigated so far. Thus, this study was designed to evaluate the Hcy effects on neonatal rat cerebellum and cerebellar oxidative stress. We also evaluated the folic acid effects on biochemical alterations elicited by hyperhomocysteinemia (hHcy) in the cerebellum. Group I received normal saline, group II received Hcy subcutaneously twice a day at 8-h intervals (0.3-0.6μmol/g body weight), group III received Hcy + folic acid (0.011μmol/g body weight), and group IV received folic acid on postnatal day (PD) 4 until 25. On day 25, superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities in the cerebellum and motor cortex were assayed. Malondialdehyde (MDA) levels were also evaluated as a marker of lipid peroxidation. Rotarod and locomotor activity tests were performed in PD 25-27. Our results indicated that administration of Hcy increased plasma, cortical, and cerebellar total Hcy levels; reduced GPx activity; and induced lipid peroxidation in the cerebellum. Hcy impaired performance on the rotarod in rats. However, treatment with folic acid significantly attenuated motor coordination impairment, GPx activity reduction, the lipid peroxidation process, and significantly reduced plasma total Hcy levels. Histological analysis indicated that Hcy could decrease Purkinje cell count and folic acid prevented this toxic effect. We conclude that Hcy can induce neurotoxicity and folic acid has neuroprotective effects against cerebellar Hcy toxicity.

Protective effect of folic acid against arsenic induced weight loss during gestation, lactation and postnatal growth in mice

Protective effect of folic acid against arsenic induced weight loss during gestation, lactation and postnatal growth in mice

Effect of valproic acid administration during pregnancy on postnatal development of cerebellar cortex and the possible protective role of folic acid.

Valproic acid (VPA), one of the most important antiepileptic drugs, proved to be inevitable for epileptic pregnant women to limit the hazards of convulsions on the foetuses and mothers. Periconceptional folic acid supple-mentation was investigated to protect against several birth defects. However, its role against VPA cerebellar toxicity was not properly investigated. The present study was conducted to evaluate the protective effect of folic acid against VPA cerebellar neurotoxicity. Twenty-four pregnant female albino rats were divided into three groups; group I (control group, did not receive any drugs), group II (given VPA at a dose of 50 mg/kg body weight once daily) and group III (given the same dose of VPA and 400 μg/kg of body weight folic acid once daily). Ten male offspring from each group were sacrificed at two ages: at 2 and 12 weeks after birth. Samples of cerebellar cortex were taken and prepared for light, electron microscopic examination, glial fibrillary acidic protein (GFAP) immunohistochemical study and histomorphometric analysis. The present study confirmed the neurotoxic effect of prenatal VPA on the cerebellar cortex, especially on Purkinje cells. The cells appeared shrunken, reduced in density, disorganised and surrounded by empty haloes. Nuclear damage and axon degeneration in the form of vacuolation, loss of organelles and absence of neurofilaments with myelin sheath depletion were detected. Concomitant supply of folic acid was shown to retain the normal architecture of Purkinje cells with their axons and nuclei. In many animals receiving folic acid, the thickness of all layers of the cortex increased up to that of the control groups, after being markedly reduced in VPA-treated groups. GFAP immunoreaction was also improved against the strong positive gliosis detected in VPA-treated groups. The present study confirmed the protective role of folic acid against the cerebellar neurotoxic effects of VPA prenatal exposure. It is recommended that folic acid supplements should be given to every epileptic pregnant mother treated with VPA. (Folia Morphol 2018; 77, 2: 201-209).

Protective effects of folic acid on DNA damage and DNA methylation levels induced by N-methyl-N'-nitro-N-nitrosoguanidine in Kazakh esophageal epithelial cells.

The protective effects of folic acid on DNA damage and DNA methylation induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in Kazakh esophageal epithelial cells were investigated using a 3 × 3 factorial design trial. The cells were cultured in vitro and exposed to media containing different concentrations of folic acid and MNNG, after which growth indices were detected. DNA damage levels were measured using comet assays, and genome-wide DNA methylation levels (MLs) were measured using high-performance liquid chromatography. The DNA methylation of methylenetetrahydrofolate reductase (MTHFR) and folate receptor-α (FRα) genes was detected by bisulfite sequencing polymerase chain reaction (PCR). The results showed significant increases in tail DNA concentration, tail length, and Olive tail moment (p < 0.01); a significant reduction of genome-wide DNA MLs (p < 0.01); and an increase in the methylation frequencies of MTHFR and FRα genes. In particular, significant differences were observed in the promoter regions of both genes (p < 0.01). Our study indicated that a reduction in folic acid concentration promotes DNA damage and DNA methylation in Kazakh esophageal epithelial cells upon MNNG exposure. Thus, sufficient folic acid levels could play a protective role against the damage induced by this compound.

Folic acid protects against experimental prenatal nicotine–induced cardiac injury by decreasing inflammatory changes, serum TNF and COX-2 expression

Nicotine administration has been shown to increase the risk for cardiovascular diseases and death. The present study was designed to investigate the impact of nicotine administration on serum level tumor necrosis factor and cycloxygenase -2 (COX-2) expression mediated cardiac injury in rat off springs, and the possible protective effect of folic acid. Eighteen pregnant female rats were randomly divided into three groups, six animals each. Control group received the vehicle, nicotine group received a dose of nicotine 0.1 mg/kg body weight, daily with subcutaneous injection from day 3 of gestation until weaning on postnatal day 21. Nicotine treated group received daily oral supplementation with folic acid 200 mg/kg body weight by intragastric tube prior to injection of nicotine. In serum of the pups, levels of tumor necrosis factor (TNF), nitric oxide (NO), total antioxidant capacity (TAC) and malondialdehyde (MDA) were measured. Histopathological studies of cardiac tissues using hematoxylin-eosin (H&E) were carried out. The expression of COX-2 was evaluated using immunohistochemistry. Serum TNF and MDA were significantly increased, while serum NO and TAC were significantly decreased in nicotine group. Moreover, nicotine-exposed rats showed complete lysis of cardiac myocytes, marked cytoplasmic vacuolation of myocytes, muscle fibers show loss of striation and increased COX-2 expression. Concomitant folic acid administration resulted in a significant alleviation of biochemical and structural alteration-induced by nicotine. In conclusion, folic acid has a protective role against nicotine induced cardiac injury by reduction of COX-2 expression, decreasing TNF production and lipid peroxidation mediated cell injury.

Histological and immunohistochemical study of the possible protective effect of folic acid on the methotrexate- induced cardiac muscle toxicity in male albino rats

Introduction: Methotrexate is widely used as a chemotherapeutic agent in cancers, ectopic pregnancies and rheumatic arthritis. Folic acid is found in dark green leafy vegetables. Methotrexate is folic acid antagonist that prevents its conversion to tetrahydro folic acid.Aim: This research aimed to study the protective effect of folic acid on the histological changes produced by methotrexate in cardiac muscles.Materials and Methods: Thirty adult male albino rats were divided into three equal groups. Group I (control group) 10 rats injected intraperitoneally with saline. Group II rats were intraperitoneally injected with methotrexate at a dose of 5mg/kg/day for one month. Group III: were intraperitoneally injected with methotrexate at a dose of (5mg/kg/day) with concomitant oral folic acid at a dose of (0.1mg/kg/day) for one month. After 24 hrs of the last dose, the animals were dissected. Hearts were processed for haematoxyline and eosine stain, immunohistochemical stains and electron microscopic examination.Results: Both degenerative and apoptotic changes were observed in the cardiac muscles in the methotrexte-treated group, these changes were attenuated by administration of folic acid.Conclusion: Folic acid is beneficial to the cardiac muscles during methotrexate treatment and should be used concomitant with methotrexate treatment.

The protective effect of folic acid and Vit B12 supplementation on albino rat lung injury due to cadmium inhalation

Background Folic acid and vitamin B12 are very important vitamins needed for normal cellular metabolic activities. Cadmium is a heavy metal that occurs naturally in the environment and Cadmium poisoning can occur through man-made pollution through agricultural and industrial activities. Aim Study of the effect of Cadmium of lung tissue of albino rats and the possible protective effect of administration of both Folic acid and vit B12 combination. Materials and Methods Thirty adult male albino rats were divided into 3 groups, a control group, Cadmium group, where rats received nebulized Cadmium chloride (CaCl2) and Cadmium + vit. group received Cadmium nebulization and both Folic acid and vit B12 supplementation. The lungs of rats of the 3 groups were collected and prepared for histopathological examination. Results Cadmium group sections showed disturbed lung architecture, shrunken alveoli and increased thickness of the alveolar wall. Vacuolation of the cytoplasm of some pneumocytes were noticed and some slides showed dilated congested blood sinusoids. Transmission electron microscopic sections revealed type II pneumocyte with hyperchromatic nucleus, perinuclear dilatation, dilated and mildly degenerated lamellar bodies. Cadmium + vit group showed that the lung tissue appears nearly normal with areas of mild thickening of the alveolar wall septa and mild edema inside alveoli. Conclusion It was concluded that both Folic acid and vit B12 supplementation proved to have a protective role against the harmful effects of Cadmium administration on the lung tissues of albino rats.

THE POTENTIAL PROTECTIVE EFFECT OF FOLIC ACID AGAINST BISPHENOL A-INDUCED TOXICITY IN PREGNANT MICE AND THEIR FETUSES

This study aimed to examine the protective effect of folic acid (FA) against bisphenol A (BPA)-induced toxicity through the hematological and biochemical parameters of pregnant mice as well as the histological and immunohistochemical alterations in the liver of pregnant mice and their fetuses. A total of 30 Albino pregnant mice were divided into three groups of 10 mice each. The first group was kept as a control. The second group was administered orally by 5 mg/kg of BPA from day 1 to 18 of gestation. The third group was administered orally by 5 mg/kg of BPA concurrently with intraperitoneal (ip) injection of FA 100 mg/kg daily from day 1 to 18 of gestation. However, BPA-treated pregnant mice showed a significant reduction in red blood cell (RBC) count, blood hemoglobin (Hb) content, hematocrit value (Ht), and white blood cell (WBC) count. Also, the serum activity of aspartate amino transferase (AST) and alanine amino transferase (ALT) levels were elevated. Treatment of pregnant mice with BPA followed by FA restored RBCs, Hb, Ht and WBCs values to nearly normal and resulted in a significant reduction in the serum activities of AST and ALT. Sever histopathological changes were observed with a significant increase in caspase-3 production in liver tissues of BPA-treated pregnant mice and their fetuses, and the FA treatment succeeded to minimize these changes with a decrease in caspase-3 production as compared to the liver of BPA-treated group. In conclusion, folic acid treatment has a protective effect and was able to reduce the negative impacts of bisphenol A-induced toxicity in pregnant mice and their fetuses.

Awareness, use and information sources of folic acid supplementation to prevent neural tube defects in pregnant Japanese women.

Folic acid supplementation and folate-rich diets are recommended for women of childbearing age worldwide to prevent congenital anomalies. We aimed to determine the current status of folic acid supplementation among pregnant Japanese women and identify means to increase the intake of these supplements. Cross-sectional study. A total of 1862 pregnant women who consulted the perinatal centre from September 2014 to December 2015 completed a questionnaire concerning knowledge about folic acid, sources of information and the use of folic acid supplements. Osaka Medical Center and Research Institute for Maternal and Child Health (Japan). In our study population, only 20·5 % of pregnant women took folic acid supplements periconceptionally even though 70·4 % knew about the protective effect of folic acid. A multivariate analysis demonstrated that age ≥35 years (OR=2·80; 95 % CI 1·24, 6·29) and knowledge of the benefits of folic acid (OR=2·64; 95 % CI 1·92, 3·62) were associated with periconceptional folic acid use, and multiparity was negatively associated with such use. Compared with those who took folic acid supplements periconceptionally, women who did not take supplements received information through passive and less interactive media. Although folic acid awareness was relatively high among pregnant Japanese women, folic acid supplementation before conception was insufficient. To increase the intake of folic acid supplements in countries in which foods are not fortified with folic acid, an effective public health approach promoting behavioural change is necessary for women of reproductive age.

The possible protective effect of folic acid against methotrexate induced ovarian damage in female albino rats. « Light and electron microscopic study

Methotrexate (MTX) is a chemotherapeutic drug that is widely used in the treatment of malignant tumors and rheumatic disorders. This work aims to study the protective effect of folic acid on the ovary affected by methotrexate. Materials and Methods: Sixty healthy, adult female albino rats were classified into six groups (10 animals each). Group I: Served as control group. Group II: The rats received folic acid in a daily oral dose of (250ug/kg b.w) for four weeks. Group III: Included rats which received an I.P injection of MTX (1mg/kg b.w) once weekly for four weeks. Group IV: The animals were concomitantly treated with MTX and FA as the same previous doses, period and routes of administration. Group V: The animals were concomitantly treated with MTX and FA as the same previous doses, routes of administration for eight weeks. Group VI: Included rats which received an I.P injection of MTX (1mg/kg b.w) once weekly for four weeks then left without treatment for another successive four weeks. Results: The following results from our study were decreased number of ovarian follicles, multiple degenerated and atretic follicles with vacuolation of the oocyte cytoplasm, disturbed oocyte in some follicles with marked apoptotic bodies inside the oocyte and granulosa cells. On the other hand, rats received folic acid (FA) following treatment with MTX revealed more or less apparent normal architecture. Conclusion: FA proved to have remarkable protective effect against toxicity of MTX by minimizing the previous degenerative changes.