Effect Of Fumaric Acid Research Articles

Effect of fumaric acid in combination with Asparagopsis taxiformis or nitrate on in vitro gas production, pH, and redox potential

Reduction in enteric methane (CH4) emissions from cattle can be achieved through use of feed additives, which often results in increased emission of hydrogen (H2). The objective of this study was to investigate in vitro effects of a known hydrogen sink, fumaric acid, in combination with either of 2 methane inhibitors, the macroalga Asparagopsis taxiformis or nitrate, on CH4 and H2 production, feed degradability, pH, and redox potential. A corn silage (0.5 g; control) was incubated in buffered rumen fluid with the addition of 0.025 g of nitrate (Nit), 0.025 g of dried A. taxiformis (Asp), 0.025 g of nitrate + 0.025 g of fumaric acid (Nit+Fum), or 0.025 g of dried A. taxiformis + 0.025 g of fumaric acid (Asp+Fum). Accumulated gas production was determined using the AnkomRF system equipped with airtight gasbags. There were 9 replicates per treatment with 3 replicates per treatment stopped after 24, 36, and 48 h of incubation. The amount of undegraded feed was determined by filtration. Gas composition was determined by gas chromatography. Degradable dry matter, degradable organic matter, pH, redox potential, and gas production data were analyzed using a mixed model. Asp and Asp+Fum reduced CH4 production by 98% or greater at all incubation times, whereas Nit and Nit+Fum reduced CH4 production (mL of CH4/g of dry matter) by 52% to 63% compared with the control. Hydrogen was only detectable in gas from Asp and Asp+Fum treatments, with no difference in H2 production between the 2 treatments. The treatments had only minor effects on redox potential in the fermented rumen fluid, and pH was lowest for treatments including A. taxiformis. In conclusion, both A. taxiformis and nitrate reduced CH4 production. Fumaric acid in combination with A. taxiformis did not reduce H2 production, and treatments including nitrate did not result in any detectable levels of H2. Future dose-response in vitro studies will contribute to investigating the potential of fumaric acid as a hydrogen sink during CH4 mitigation.

The effects of fumaric acid on in vitro true digestibility of tea wastes produced with different cultivation methods

This study aims to determine the effects of adding different fumaric acid (FA) levels to tea factory wastes (TFW) produced by different cultivation methods on in vitro true digestibility. In vitro true digestibility of feed (IVTDAs feed), dry matter (IVTDDM), organic matter (IVTDOM), and neutral detergent fibre (IVTDNDF) were performed with a Daisy Incubator. Fumaric acid did not add to the control group and added 0.1%, 0.2%, or 0.3% FA to the experimental groups. When the cultivation methods were compared (conventional and organic tea wastes), it was seen that FA made a significant difference (P0.05). There was a significant difference (P

Effect of fumaric acid on the growth of Lactobacillus delbrueckii ssp. bulgaricus during yogurt fermentation

Yogurt is traditionally fermented by a symbiotic starter culture of Streptococcus thermophilus and Lactobacillus delbrueckii ssp. bulgaricus. These bacteria exchange metabolites with each other to meet their nutritional demands during protocooperation, resulting in a shorter fermentation time. In this study, we investigated whether fumaric acid functions as a symbiotic agent to promote the growth of Lb. bulgaricus by evaluating 8 strains of Lb. bulgaricus and 7 strains of Strep. thermophilus. All the tested Lb. bulgaricus strains metabolized the added fumaric acid into succinic acid during monoculture in milk, and 6 strains (75%) showed shorter fermentation time compared with the control. The addition of malic acid showed similar trends as that of fumaric acid, indicating that the reverse tricarboxylic acid cycle was functioning in Lb. bulgaricus. All 7 Strep. thermophilus strains tested produced fumaric acid during monoculture in milk. Further, in Lb. bulgaricus 2038, the gene expression of fumarate reductase that converts fumaric acid to succinic acid, was higher in the coculture with Strep. thermophilus 1131 than in the monoculture. These findings indicate that fumaric acid produced by Strep. thermophilus can function as a symbiotic substance during yogurt fermentation to stimulate the growth of Lb. bulgaricus.

Fumaric Acids Do Not Directly Influence Gene Expression of Neuroprotective Factors in Highly Purified Rodent Astrocytes.

(1) Background: Dimethylfumarate (DMF) has been approved for the treatment of relapsing remitting multiple sclerosis. However, the mode of action of DMF and its assumed active primary metabolite monomethylfumarate (MMF) is still not fully understood. Former reports suggest a neuroprotective effect of DMF mediated via astrocytes by reducing pro-inflammatory activation of these glial cells. We investigated potential direct effects of DMF and MMF on neuroprotective factors like neurotrophic factors and growth factors in astrocytes to elucidate further possible mechanisms of the mode of action of fumaric acids; (2) Methods: highly purified cultures of primary rat astrocytes were pre-treated in vitro with DMF or MMF and incubated with lipopolysaccharides (LPS) or a mixture of interferon gamma (IFN-γ) plus interleukin 1 beta (IL-1β) in order to simulate an inflammatory environment. The gene expression of neuroprotective factors such as neurotrophic factors (nuclear factor E2-related factor 2 (NGF), brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF)) and growth factors (fibroblast growth factor 2 (FGF2), platelet-derived growth factor subunit A (PDGFa), ciliary neurotrophic factor (CNTF)) as well as cytokines (tumor necrosis factor alpha (TNFα), interleukin 6 (IL-6), IL-1β, inducible nitric oxide synthase (iNOS)) was examined by determining the transcription level with real-time quantitative polymerase chain reaction (qPCR); (3) Results: The stimulation of highly purified astrocytes with either LPS or cytokines changed the expression profile of growth factors and pro- inflammatory factors. However, the expression was not altered by either DMF nor MMF in unstimulated or stimulated astrocytes; (4) Conclusions: There was no direct influence of fumaric acids on neuroprotective factors in highly purified primary rat astrocytes. This suggests that the proposed potential neuroprotective effect of fumaric acid is not mediated by direct stimulation of neurotrophic factors in astrocytes but is rather mediated by other pathways or indirect mechanisms via other glial cells like microglia as previously demonstrated.

Effects of fumaric acid on rumen fermentation, milk composition and metabolic parameters in lactating cows

The aim of this study was to determine the influence of fumaric acid (FA) on ruminal fermentation and its effects on the acid-base balance of seven ruminally and duodenally fistulated multiparous German Holstein cows. The experiment was conducted in a change-over design with three periods in which the animals were randomly arranged in one of three treatments: Control (C; without FA), 300 or 600g FA per day. The diets consisted of 7.4kg DM grass silage, 4.2kg concentrate mixture and 0, 300 or 600g FA or wheat starch as isocaloric compensation per day and cow. FA supplementation decreased the rumen pH, acetic acid and butyric acid and increased propionic acid in rumen fluid. The results of the single-strand conformation polymorphism analysis (SSCP) did not show an influence of FA on the microbial population in the rumen. The beta-hydroxybutyrate (BHB) concentration in blood and the pH of the urine decreased, while the blood gases were unaffected by supplementation of the acid. The microbial protein per MJ ME decreased in the duodenum with FA supplementation. The milk fat concentration decreased after addition of FA. We conclude that in this study feeding of up to 600g FA per day did not result in an acidosis. It seems that up to 600g FA per day did not have a significant influence on the acid-base balance of dairy cows.

Studies on potential effects of fumaric acid on rumen microbial fermentation, methane production and microbial community

The greenhouse gas methane (CH4) contributes substantially to global climate change. As a potential approach to decrease ruminal methanogenesis, the effects of different dosages of fumaric acid (FA) on ruminal microbial metabolism and on the microbial community (archaea, bacteria) were studied using a rumen simulation technique (RUSITEC). FA acts as alternative hydrogen acceptor diverting 2H from methanogenesis of archaea towards propionate formation of bacteria. Three identical trials were conducted with 12 fermentation vessels over a period of 14 days. In each trial, four fermentation vessels were assigned to one of the three treatment groups differing in FA dosage: low fumaric acid (LFA), high fumaric acid (HFA) and without FA (control). FA was continuously infused with the buffer. Grass silage and concentrate served as substrate. FA led to decreases in pH and to higher production rates of total short chain fatty acids (SCFA) mediated by increases in propionate for LFA of 1.69 mmol d−1 and in propionate and acetate production for HFA of 4.49 and 1.10 mmol d−1, respectively. Concentrations of NH3-N, microbial crude protein synthesis, their efficiency, degradation of crude nutrients and detergent fibre fraction were unchanged. Total gas and CH4 production were not affected by FA. Effects of FA on structure of microbial community by means of single strand conformation polymorphism (SSCP) analyses could not be detected. Given the observed increase in propionate production and the unaffected CH4 production it can be supposed that the availability of reduction equivalents like 2H was not limited by the addition of FA in this study. It has to be concluded from the present study that the application of FA is not an appropriate approach to decrease the ruminal CH4 production.

Ácido fumárico e sua combinação com ácido lático ou propionato de cálcio em dietas de leitões recém-desmamados

Avaliou-se o efeito da adição dos ácidos fumárico, lático e propionato de cálcio ou suas combinações sobre o desempenho, pH estomacal, pH duodenal, morfologia e morfometria do intestino delgado de leitões desmamados aos 15 dias de idade. Foram utilizados 180 leitões, 90 machos castrados e 90 fêmeas, com média de peso inicial de 4,78±1,19kg, distribuídos em delineamento de blocos ao acaso. Utilizaram-se cinco tratamentos: T1 - ração controle (RC); T2 - RC + 0,5% de ácido fumárico; T3 - RC + 0,5% de ácido fumárico + 1,0% de propionato de cálcio; T4 - RC + 0,5% de ácido fumárico + 1,0% de ácido lático; T5 - RC + 0,5% de ácido fumárico + 0,5% de propionato de cálcio + 0,5% de ácido lático, com seis repetições e seis animais por unidade experimental. Não houve influência (P>0,05) dos tratamentos sobre o ganho de peso diário (GPD), consumo de dieta diário (CRD) e conversão alimentar (CA). Quanto ao epitélio intestinal, não houve diferenças (P>0,05) entre tratamentos em relação à altura do epitélio do duodeno, jejuno e íleo. Não houve efeito dos tratamentos (P>0,05) sobre o pH do estômago e do jejuno. A inclusão do ácido fumárico não influenciou o desempenho dos leitões.

Combined treatment of fumaric acid with aqueous chlorine dioxide or UV-C irradiation to inactivate Escherichia coli O157:H7, Salmonella enterica serovar Typhimurium, and Listeria monocytogenes inoculated on alfalfa and clover sprouts

Abstract Effect of fumaric acid, chlorine dioxide (ClO2), and UV-C treatment was examined on the inactivation of microorganisms in alfalfa and clover sprouts. Clover sprouts were irradiated with UV-C light (1–10 kJ/m2), and the treatment decreased the population of total aerobic bacteria by 1.03–1.45 log CFU/g. Clover sprouts inoculated with pathogenic bacteria were treated with various concentration of fumaric acid, and 0.5 g/100 ml fumaric acid treatment was the most effective. In addition, the combined treatment of fumaric acid (0.5 g/100 ml)/UV-C (1 kJ/m2) reduced the populations of Escherichia coli O157:H7, Salmonella enterica serovar Typhimurium, and Listeria monocytogenes inoculated on clover sprouts by 3.02, 2.88, and 2.35 log CFU/g. Alfalfa sprouts were treated with ClO2, fumaric acid, and the combination of fumaric acid/ClO2. The combined treatment was the most effective, and it reduced the total aerobic bacteria by 3.18 log CFU/g as well as the initial populations of E. coli O157:H7, S. typhimurium, and L. monocytogenes inoculated on alfalfa sprouts by 4.06, 3.57, and 3.69 log CFU/g. These results suggest that the combined treatment of fumaric acid with UV-C or ClO2 can be useful for improving the microbial safety of alfalfa and clover sprouts.

Methane emissions from beef cattle: Effects of fumaric acid, essential oil, and canola oil1

The objective of this study was to identify feed additives that reduce enteric methane emissions from cattle. We measured methane emissions, total tract digestibility (using chromic oxide), and ruminal fermentation (4 h after feeding) in growing beef cattle fed a diet supplemented with various additives. The experiment was designed as a replicated 4 x 4 Latin square with 21-d periods and was conducted using 16 Angus heifers (initial BW of 260 +/- 32 kg). Treatments were: control (no additive), fumaric acid (175 g/d) with sodium bicarbonate (75 g/d), essential oil and spice extract (1 g/d), or canola oil (4.6% of DMI). The basal diet consisted of 75% whole-crop barley silage, 19% steam-rolled barley, and 6% supplement (DM basis). Four large chambers (2 animals fed the same diet per chamber) were equipped to measure methane emissions for 3 d each period. Adding canola oil to the diet decreased (P = 0.009) total daily methane emissions by 32% and tended (P = 0.09) to decrease methane emissions as a percentage of gross energy intake by 21%. However, much of the reduction in methane emissions was due to decreased (P < 0.05) feed intake and lower (P < 0.05) total tract digestibility of DM and fiber. Digestibility of all nutrients was also lowered (P < 0.05) by feeding essential oil, but there were no effects on ruminal fermentation or methane emissions. In contrast, adding fumaric acid to the diet increased total VFA concentration (P = 0.03), increased propionate proportions (P = 0.01), and decreased the acetate:propionate ratio (P = 0.002), but there was no measurable effect on methane emissions. The study demonstrates that canola oil can be used to reduce methane losses from cattle, but animal performance may be compromised due to lower feed intake and decreased fiber digestibility. Essential oils had no effect on methane emissions, whereas fumaric acid caused potentially beneficial changes in ruminal fermentation but no measurable reductions in methane emissions.

Effect of fumaric acid on diet digestibility and the caecal environment of growing rabbits

L'addition d'acide fumarique a deux doses distinctes (5 et 10 g par kg, LFA et HFA) dans le regime de lapins en croissance a ete comparee, en termes de digestibilite apparente des nutriments et de contenu caecal, a l'addition d'une dose sub-therapeutique de bacitracine-zinc (25 ppm, BAC) et a un traitement temoin (CTL). La digestibilite de la matiere seche (DMD) et celle de la matiere organique (OMD) n'ont pas ete significativement differentes entre les regimes contenant l'acide fumarique et les regimes BAC et CTL, seules des differences ont ete observees entre les regimes LFA et HFA (DMD : P = 0,05 et OMD : P = 0,07). La digestibilite des parois (NDF) n'a pas ete affectee par les traitements (P < 0,10) alors que la quantite d'azote microbien ingeree issue des caecotrophes a eu tendance a etre plus elevee (P = 0,09) avec les regimes LFA et HFA et a augmenter avec la dose d'acide fumarique. Bien qu'aucune difference n'ait ete mise en evidence entre les regimes pour le nombre total de bacteries dans le contenu caecal, la concentration des bacteries amylolytiques a ete superieure avec les regimes LFA et HFA comparativement au regime BAC (P =0,08).

Effect of Fumaric Acid, Its Dimethylester, and Topical Antipsoriatic Drugs on Epidermal Differentiation in the Mouse Tail Model

Fumaric acid, fumaric acid dimethylester, and the dithranol derivative C4-lactone were studied in the mouse tail test to evaluate their effects on epidermal cell differentiation compared with other topical antipsoriatic drugs, such as betamethasone, calcipotriol, and dithranol. Mouse tails were treated for 2 weeks and longitudinal histological sections prepared of the tail skin. The length of the orthokeratotic regions (stratum granulosum) was measured on 10 sequential scales per tail and expressed as percentage of the full length of the scale. In addition, epidermal thickness was measured and the efficacy of the various compounds evaluated. In comparison to 2% salicylic acid ointment, all tested compounds except fumaric acid significantly (p < or = 0.05) increased the proportion of the orthokeratotic region. C4-lactone and calcipotriol were less effective than dithranol, fumaric acid dimethylester only moderately influenced cell differentiation, and betamethasone showed the least potent effect. Dithranol was the most potent substance inducing orthokeratosis without increasing epidermal thickness.

Antifungal Activity of Fumaric Acid in Mice Infected with Candida albicans.

An examination was made on the effect of fumaric acid on an experimental systemic candidiasis. Male ICR mice were innoculated into the tail veins with 10(6) yeast cells of Candida albicans and treated with daily intraperitoneal injections of fumaric acid at the dose of 40 mg/kg/d. The results indicated that the administration of fumaric acid was effective in prolonging the survival of animals after the fungal challenge and prevented one-fifth of the treated animals from dying of candidiasis.

Inhibitory Effect of Fumaric Acid on Hepatocarcinogenesis by Thioacetamide in Rats

An inhibitory effect of fumaric acid (FA) on hepatocarcinogenesis was examined in rats fed thioacetamide (TAA). A group of male DONRYU rats were fed TAA at a level of 0.035% in the diet for 40 weeks and then fed a basal diet for 40 weeks. Hepatic carcinomas developed in 9 of 41 animals of this group fed TAA alone. The effect of FA on the carcinogenesis was examined in 2 groups fed both TAA and FA; one group of rats were fed FA at 1% in a basal diet after ingestion of TAA, and another group of rats were fed TAA plus a supplement of 1% FA in the diet. The inhibitory effect of FA on TAA carcinogenesis was so marked that no hepatic carcinomas were found in both groups fed FA in combination with TAA.

Inhibitory Effect of Fumaric Acid on 3-Methyl-4′-(dimethylamino)azobenzene-Induced Hepatocarcinogenesis in Rats

Fumaric acid (FA) was examined for its effect on hepatocarcinogenesis in rats fed 3-methyl-4'-(dimethylamino)azobenzene (3-Me-DAB). Male DONRYU rats were given approximately 0.5 g 3-Me-DAB by being fed a diet containing 0.06% 3-Me-DAB for 50 days; they were then given a diet containing 1% FA and drinking water containing 0.025% FA for 51 weeks. The administration of FA effectively suppressed the development of hepatocellular carcinoma, hyperplastic nodules, and hyperplastic areas in the livers of rats fed 3-Me-DAB.

Inhibitory Effect of Fumaric Acid on Forestomach and Lung Carcinogenesis by a 5-Nitrofuran Naphthyridine Derivative in Mice

The inhibitory effect of fumaric acid (FA) on carcinogenesis by potassium 1-methyl-7-[2-(5-nitro-2-furyl)vinyl]-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate (trans, NFN) was examined histologically with male ICR/JCL mice. NFN was fed to mice at a dose level of 0.012% in the diet for 14 weeks. These mice were then divided into 2 groups. One group was given a basal diet, and the other group was given a diet containing 1% FA in the subsequent 39 weeks. In the group of 30 mice fed NFN alone, squamous cell carcinomas were found in the stomachs of 7 mice, multiple papillomas in the stomachs of 13 mice, and multiple and large papillary adenocarcinomas in the lungs of 27 animals. The administration of FA suppressed the NFN-induced stomach and lung carcinogenesis. In the group of 32 mice fed NFN and FA, no stomach tumors developed except 1 early-stage of squamous cell carcinoma. In the lungs, only a small focus of mild atypical hyperplasia and a few early-stage adenocarcinomas were noted in 7 and 11 animals, respectively.

Inhibiting Malo-Lactic Fermentation in Australian Dry Red Wines by Adding Fumaric Acid

Added fumaric acid delayed bacterial malo-lactic fermentation in three young Australian commercial dry red wines from <i>Vitis vinifera</i> L., `Shiraz9 variety, grown in different wine areas in South Australia (Berri, hot region; Adelaide, warm region; and Coonawarra, cool region). The delay increased with the concentration of fumaric acid (up to 1.5 g/l), and the increase was synergistic (multiplicatively) with decreasing pH (4.1 to 3.5). The wines themselves varied somewhat in the effect of fumaric acid. The acid proved bactericidal to added wine leuconostocs, drastically reducing the numbers of viable bacteria in two days. In many cases the wines with fumaric acid addition had not undergone malo-lactic fermentation by 41 weeks even though conditions were ideal for bacterial growth: storage at 25°C, no added sulfur dioxide, and no removal of yeast sediment. When malo-lactic fermentation occurred, both fumaric acid and L-malic acid were degraded. The acids were converted stoichiometrically to L-lactic acid — one mole of substrate resulting in one mole L-lactic acid. The probable pathway of fumaric acid degradation by the wine leuconostocs in the fermentation is by conversion to L-malic acid catalyzed by fumarase, with subsequent malo-lactic fermentation yielding L-lactic acid and carbon dioxide.

The Effect of Fumaric Acid on Malo-Lactic Fermentation in Wines from Warm Areas

Wines made from grapes from warm areas such as the San Joaquin Valley would seldom seem to benefit from malo-lactic fermentation. Not only is acidity lost but off-odors and off-flavors can develop which are sometimes difficult to remove. Most wines from these areas are sold young, without aging, and part of their value is their fresh fruitiness. Fumaric acid has been shown (3, 8) to be effective in delaying or inhibiting the growth of malo-lactic bacteria in wine. Earlier work (5) had indicated that quality difference in wines might depend on the species of malo-lactic bacteria present. This paper demonstrates that routine addition of fumaric acid at the time of the first racking, along with a normal addition of sulfur dioxide, will in general improve wine quality significantly by inhibiting malo-lactic fermentation as well as adding needed acid to the wines. In addition, the usual recommended malo-lactic strain (<i>Leuconostoc oenos</i> ML-34) was tested to see whether it did improve wine quality over that obtained by allowing a natural flora to develop.

The Effect of Fumaric Acid on Malo-Lactic Fermentation

Additions of fumaric acid greater than 3 lb per 1000 gallons retarded malo-lactic fermentation in 9Malbec9 and 9Pinot noir9 wines. Fumaric and citric acids, as determined by paper chromatography, disappeared during the malo-lactic fermentation. There was no significant increase in lactic acid although fumarase has been reported present. All malo-lactic fermentations were carried out with Leuconostoc ciltrovorum (ML-34).