Fulvic Acid

The present study investigated the impacts of dissolved organic matters (DOM) on joint toxicity involved in zinc oxide nanoparticles (ZnO NPs) and tetrabromobisphenol A (TBBPA) at relevant low-exposure concentrations (<1 mg/L). It was found that ZnO NPs in single and combined systems exhibited severe inhibition effects on a freshwater microalgae Scenedesmus obliquus. However, the presence of DOM slightly alleviated the growth inhibition toxicity induced by the binary mixtures of ZnO NPs and TBBPA. Ultrastructure analysis revealed that ZnO NPs caused structural damage to cells, including plasmolysis, membrane destruction, and the disruption of thylakoid in the chloroplast, regardless of the presence of coexisting substances. Oxidative stress biomarker quantitative analysis and in situ observations indicated that the massive accumulation of reactive oxygen species in the binary mixtures of ZnO NPs and TBBPA caused severe oxidative damage, but the presence of DOM significantly mitigated the damage.

This study investigated the impact of dissolved organic matters (DOM) on the ecological toxicity of aluminum oxide nanoparticles (Al2O3NPs) at a relatively low exposure concentration (1 mg L-1). The unicellular green alga Scenedesmus obliquus was exposed to Al2O3NP suspensions in the presence of DOM (fulvic acid) at various concentrations (1, 10, and 40 mg L-1). The results show that the presence of DOM elevated the growth inhibition toxicity of Al2O3NPs towards S. obliquus in a dose-dependent manner. Moreover, the combination of DOM at 40 mg L-1 and Al2O3NPs resulted in a synergistic effect. The relative contribution of Al-ions released from Al2O3NPs to toxicity was lower than 5%, indicating that the presence of the particles instead of the dissolved ions in the suspensions was the major toxicity sources, regardless of the presence of DOM. Furthermore, DOM at 10 and 40 mg L-1 and Al2O3NPs synergistically induced the upregulation of intercellular reactive oxygen species levels and superoxide dismutase activities. Analysis of the plasma malondialdehyde concentrations and the observation of superficial structures of S. obliquus indicated that the mixtures of DOM and Al2O3NPs showed no significant effect on membrane lipid peroxidation damage. In addition, the presence of both DOM and Al2O3NPs contributed to an enhancement in both the mitochondrial membrane potential and the cell membrane permeability (CMP) in S. obliquus. In particular, Al2O3NPs in the presence of 10 and 40 mg L-1 DOM caused a greater increase in CMP compared to Al2O3NPs and DOM alone treatments. In conclusion, these findings suggest that DOM at high concentrations and Al2O3NPs synergistically interrupted cell membrane functions and triggered subsequent growth inhibition toxicity.

Standard static-exposure acute lethality tests were conducted with Daphnia magna neonates exposed to binary or ternary mixtures of Cd, Cu, and Zn in moderately hard reconstituted water that contained 3 mg dissolved organic carbon/L added as Suwannee River fulvic acid. These experiments were conducted to test for additive toxicity (i.e., the response to the mixture can be predicted by combining the responses obtained in single-metal toxicity tests) or nonadditive toxicity (i.e., the response is less than or greater than additive). Based on total metal concentrations (>90% dissolved) the toxicity of the tested metal mixtures could be categorized into all 3 possible additivity categories: less-than-additive toxicity (e.g., Cd-Zn and Cd-Cu-Zn mixtures and Cd-Cu mixtures when Cu was titrated into Cd-containing waters), additive toxicity (e.g., some Cu-Zn mixtures), or more-than-additive toxicity (some Cu-Zn mixtures and Cd-Cu mixtures when Cd was titrated into Cu-containing waters). Exposing the organisms to a range of sublethal to supralethal concentrations of the titrated metal was especially helpful in identifying nonadditive interactions. Geochemical processes (e.g., metal-metal competition for binding to dissolved organic matter and/or the biotic ligand, and possibly supersaturation of exposure waters with the metals in some high-concentration exposures) can explain much of the observed metal-metal interactions. Therefore, bioavailability models that incorporate those geochemical (and possibly some physiological) processes might be able to predict metal mixture toxicity accurately. © 2014 SETAC.

The protective effect of dissolved organic matter (DOM) on metal toxicity to aquatic organisms has been reported by numerous authors. Bioavailability models such as the biotic ligand model (BLM) thus account for this factor to predict metal toxicity to aquatic organisms. Until now, however, few attempts have been made to assess the effect of the DOM source on metal speciation and toxicity and, accordingly, on BLM predictions. The aims of this study were to investigate to what extent DOMs differ in their ability to decrease acute copper toxicity to the cladoceran Daphnia magna and to evaluate if ultraviolet (UV) absorbance measurements may be a simple and effective method to incorporate DOM variability into the acute Cu-BLM for D. magna. Acute toxicity tests were carried out in artificial test water enriched with DOMs isolated from six locations in Europe and North America and in seven natural European surface waters. The acute Cu-BLM for D. magna was then used to estimate the copper complexing capacity of each DOM (expressed as % active fulvic acid, %AFA). A factor of 6 difference was observed between the lowest and the highest copper complexing capacity. A significant linear relationship was observed between the UV-absorbance coefficient at 350 nm (epsilon350) and the %AFA. Linking this relationship to the acute Cu-BLM resulted in a significant improvement of the predictive capacity of this BLM. Without accounting for this relationship, 90% of the predicted 48-h 50% effective concentrations (EC50) were within a factor of 2 of the observed EC50s; taking this relationship into account, 90% of the EC50s were predicted with an error of less than factor 1.3. The present study and other studies seem to indicate that UV absorbance may be a good measure of biologically and toxicologically relevant differences in copper binding behavior of DOM.

Accumulation and growth inhibition of Cu to fresh water alga (Scenedesmus subspicatus 86.81 SAG) and the influences of ethylenediaminetetraacetic acid (EDTA) and fulvic acid (FA) were examined. These results demonstrated that both EDTA and FA could reduce toxicity of Cu to alga by the way of preventing Cu from being adsorbed by cell wall of alga. When dissolved Cu (Cu(dissolved)), extracellular Cu (Cu(extracellular)), and intracellular Cu (Cu(intracellular)) were differentiated, our results showed that the concentration level of extracellular Cu ([Cu(extracellular)]) was a good indicator for measuring the toxic effects of Cu on alga growth in complex matrix. Either in the absence or in the presence of EDTA and FA, the concentration of intracellular Cu increased to 0.6-1.5 x 10(-8) microM per cell when the growth inhibition reached to about 50%. We found that the acute toxicity of copper on unicellular alga could be interpreted by its accumulation at a discrete site or biotic ligand at alga cell wall and critical accumulation of Cu associated with EC(50) was determined to be 1 x 10(-8) microM per cell. Therefore, the Biotic Ligand Model (BML) could be extended to predict the influence of copper on growth inhibition of alga.

The hypothesis, that metal toxicity is dominated by free ion activity, was tested by comparing calculated metal activities with measured toxic responses to a genetically modified, luminescent bacterium, Escherichia coli. The toxicity of Cd, Cu, and Zn sulphate salts in the presence of EDTA and fulvic acid in well-defined solutions was measured. Good agreement between free metal activity and toxicity was found for Cu but not for Zn and Cd. The toxicity relationships were altered by glucose addition to the organism. Stable chloride complexes may have contributed to the toxicity of Cd under the test conditions. The results suggest that there is not always a simple relationship between toxicity and free-ion metal concentration and that further account should be taken of competitive interactions between living cells and ligands and the physiological status of the organism.

Protocatechuic acid can be oxidized and polymerized to from humic substances (humic acid and fulvic acid). Should AS2O3 occur in the process of oxidative polymerization, humic acid output can increase by 1.5 - 2.3 times and, in the case of fulvic acid, at least 10 times. After protocatechuic acid is oxidized and polymerized, the resultant humic and fulvic acids both exhibit the ability to shorten the prothrombin time of human pool plasma in vitro. This ability becomes more apparent when AS2O3 serves as a promoter in the course of oxidative polymerization as described above. However, AS2O3 or protocatechuic acid alone is unable to shorten the prothrombin time of human pool plasma.

101. Mutat Res. 1987 Feb;176(2):199-204. doi: 10.1016/0027-5107(87)90050-9. Mechanism of the desmutagenic effect of humic acid. Sato T, Ose Y, Nagase H, Hayase K. The mechanism of an apparent desmutagenic effect of humic acid was investigated. Firstly, components of humic acid (resorcinol, vanillin, vanillic acid, ferulic acid, protochatechuic acid and benzoic acid) were tested and were not found to show a desmutagenic effect. By contrast, lignin did show a desmutagenic effect. The desmutagenic effect of humic acid was decreased by ozone treatment, and the degree of decrease corresponded with a decrease in KMnO4 consumption. Benzo[a]pyrene and humic acid were incubated at 37 degrees C for 1 h and extracted by ethyl acetate and the extract was investigated by gas chromatography (GC). The peak of the decomposition product did not appear, but the amount of benzo[a]pyrene was decreased. This suggests that the desmutagenic effect of humic acid was caused by adsorption of benzo[a]pyrene by humic acid rather than by decomposition of benzo[a]pyrene. Humic acid had the largest adsorption activity at its critical micelle concentration (CMC), while adsorbed benzo[a]pyrene could be released by ultrasonication. Fulvic acid and water-soluble humic substance showed a slight inhibitory effect on the mutagenicity of benzo[a]pyrene.

Alzheimer's disease (AD) is a brain disorder displaying a prevalence and impact in constant expansion. This expansive and epidemic behavior is concerning medical and public opinion while focusing efforts on its prevention and treatment. One important strategy to prevent this brain impairment is based on dietary changes and nutritional supplements, functional foods and nutraceuticals. In this review we discuss the potential contributions of shilajit and complex B vitamins to AD prevention. We analyze the status of biological studies and present data of a clinical trial developed in patients with mild AD. Studies suggest that shilajit and its active principle fulvic acid, as well as a formula of shilajit with B complex vitamins, emerge as novel nutraceutical with potential uses against this brain disorder.

Rainbow trout (Oncorhynchus mykiss) is an important fish species raised in aquaculture, but it is susceptible to stress, infections diseases. The present study aimed to determine the effects of fulvic acid feed addition on the systemic and mucosal protective mechanisms of juvenile rainbow trout and to elucidate the underlying molecular mechanisms of changes in the gut. Rainbow trout (4.30 ± 0.6 g) diet was supplemented with different levels of fulvic acid: 0% (Control), 0.5%, 1% and 2%. At the end of 8-week feeding trial, growth parameters such as final weight gained weight (%), SGR (F1%) increased, and FCR (all levels) decreased significantly compared to the control group. We found that the activity of lysozyme, glutathione peroxidase, and catalase in the serum were significantly improved, especially after the addition of 0.5% and 1% of fulvic acid. At the same time, the immunoglobulin concentration in the skin mucus was increased with 0.5% supplementation. However, the expression of tnf-α, il-6 and gpx in the intestine was strongly upregulated after supplementation with 2%, indicating oxidative stress and inflammation with this level of fulvic acid inclusion. Furthermore, the mucus lysozyme activity was reduced at this concentration, which can increase the susceptibility to pathogen invasion. The results suggest that adding 0.5%-1% of fulvic acid to the feed of juvenile rainbow trout can help to improve their immune and antioxidative defenses and thereby support the wellbeing of fish. © 2025 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.

To study the effects of mineral fulvic acid (FuA) on broiler performance, slaughter performance, blood biochemistry index, antioxidant function, immune performance, and intestinal microflora, 360 Arbor Acres (AA) broiler chickens with similar body weights were randomly divided into 5 groups with 6 replicates in each group and 12 chickens in each replicate in the current study. Chickens in the control group (C) were fed with the basal diet, and chickens in the test groups (I, II, III, and IV) were fed with the diet supplemented with 0.05%, 0.1%, 0.2%, and 0.3% mineral FuA, respectively. The indicators were measured on the hatching day, d 21 and d 35. From the whole experimental period, FuA supplement significantly increased average body weight (ABW) (P < 0.05), average daily gain (ADG) of broilers (P < 0.05), and thymus weight (P < 0.05) in II and IV groups, but bascially reduced the pH value of thigh meat. FuA supplement significantly improved aspartate aminotransferase (AST) activity in the group III on d 35 (P < 0.05) and the serum levels of IgA and IgG on d 21 and d 35 (P < 0.05), but reduced glutathione peroxidase (GSH-Px) level on d 21 (P < 0.05) and malondialdehyde (MDA) level in serum on d 35 (P < 0.05). FuA supplement significantly affected the abundance of Barnesiella, Lachnospiraceae, Alistipes, Lactobacillus, and Christensenellaceae on genus level. Differences between group III and other groups were significant in the genera microflora composition on d 21 and d 35. Functional analysis showed that the cecum microbiota were mainly enriched in carbohydrate metabolism, amino acid metabolism, and energy metabolism. In conclusion, FuA may potentially have significant positive effects on the growth performance and immune function of AA chickens through the modulation of the gut microbiota, and the 0.1% FuA was the best in broiler diet based on the present study.

Two experiments were conducted to investigate the effects of sodium sulfate water and the efficacy of nonnutritive feed additives in nursery pig diets. In Exp. 1, 320 barrows (5.4 ± 0.1 kg BW and 21 d of age) were allotted to 1 of 8 treatments for 24 d in a 2 × 4 factorial with 2 levels of sodium sulfate water (control or 3,000 mg sodium sulfate/L added), and 4 dietary zeolite (clinoptilolite) levels (0, 0.25, 0.50, or 1%). Fecal samples were collected on d 5, 9, 16, and 23; visually scored for consistency (1 = firm and 5 = watery); and analyzed for DM. No interactions of sodium sulfate × zeolite were observed for any response criteria. Overall (d 0 to 24), pigs drinking sodium sulfate water had decreased (P < 0.01) ADG, ADFI, and G:F compared with pigs drinking control water. Pigs drinking sodium sulfate water also had increased (P < 0.01) fecal scores and lower (P < 0.04) fecal DM on d 5, 9, and 16 compared with pigs drinking control water. Increasing dietary zeolite increased (linear; P < 0.05) ADG and ADFI but had no effect on G:F. In Exp. 2, 350 barrows (5.7 ± 0.1 kg BW and 21 d of age) were allotted to 1 of 10 treatments in a 2 × 5 factorial for 21 d with 2 levels of sodium sulfate water (control or 2,000 mg sodium sulfate/L added) and 5 dietary treatments (control, 1 or 2% zeolite, 1% humic acid substance [HA], and 1% humic and fulvic acid substance [HFB]). Fecal samples were collected on d 5, 8, 15, and 21; visually scored for consistency (1 = firm and 5 = watery); and analyzed for DM. Overall (d 0 to 21), a water source × diet interaction was observed for ADG and G:F because pigs fed the 1% HA had decreased (P < 0.01) ADG and G:F when drinking sodium sulfate water compared with other treatments but increased ADG and G:F when drinking control water. Pigs drinking sodium sulfate water had decreased (P < 0.01) ADG and G:F and tended (P < 0.08) to have decreased ADFI compared with pigs drinking control water. Pigs drinking sodium sulfate water had increased (P < 0.01) fecal scores and decreased (P < 0.01) fecal DM on d 5 and 8. In conclusion, water high in sodium sulfate concentrations decreased growth performance and increased fecal moisture in newly weane

OBJECTIVE: To examine the effects of a dietary humic and fulvic acid complex, FeedMAX 15, on the health, growth rate, feed conversion ratio, and carcase characteristics of feedlot cattle. DESIGN: Cattle, in eight pens of 125 animals each, were fed either a diet containing a humic and fulvic acid complex (FeedMAX 15, FeedMAX Industries, Toowoomba, Queensland) or the same diet without the additive. Control or FeedMAX 15 diets were allocated to each pen at random. Individual cattle were allocated alternately to control or treatment pens based on order of presentation. Comparisons of disease incidence, mortality, feed intake, growth rate, feed conversion ratio, fat depth, dressing percentage, meat colour, fat colour and marbling were made at the conclusion of the feeding period. RESULTS: No differences were found between cattle fed FeedMAX 15 and cattle not fed the additive in entry body weight (P = 0.99), exit body weight (P = 0.91), dressing percentage (P = 0.66), P8 fat depth (P = 0.57), meat colour (P = 0.67), marbling (P = 0.70), all diseases (P = 0.64), bovine respiratory disease (P = 0.91), or mortalities (P = 1.0). Cattle fed FeedMAX 15 reached the market specifications for body weight and fat depth in fewer mean days (P = 0.0001), had a greater average daily gain (P = 0.05), a lower feed conversion ratio (P = 0.05) and whiter fat (P < 0.0001). CONCLUSIONS: Feeding the humic and fulvic acid complex, FeedMAX 15, at 0.055 g per kg body weight per day, can increase growth rate and feed conversion efficiency in feedlot cattle.