A study on the effect of deoxynivalenol on serotonin receptor binding in fig brain membranes

Abstract

Central serotoninergic (5‐hydroxytryptamine, 5HT) pathways are believed to be involved in the mechanisms of anorexia and/or emesis evoked by the trichothecene mycotoxin deoxynivalenol (DON). Using an in vitro membrane receptor binding assay, the competitive potency of DON was investigated against several radioactive ligands that have a high affinity for selective 5HT‐receptor subgroups. Receptor site densities and displacement profiles in twelve selected regions of pig brain were investigated. Overall, DON possessed only minimal efficacy to competently block any of the 5HT‐ligands tested. IC₅₀ values (50% inhibitory concentration) of at least 5 mM DON were required to inhibit binding, and in certain regions concentrations of 100 mM were ineffective. In comparison, several standard 5HT‐antagonists showed 10³‐10⁵ times greater capability than DON to displace binding of these ligands. Because these results indicated DON possesses only weak affinity for the 5HT‐receptor subtypes investigated here, this suggested that in vivo, unless relatively high concentrations of the toxin are present, its pharmacological effects may be mediated by mechanisms other than a functional interaction with serotoninergic receptors at the central level.     

Effect of the appetite stimulant cyproheptadine on deoxynivalenol ‐ induced reductions in feed consumption and weight gain in the mouse 1

Abstract

Deoxynivalenol (DON, vomitoxin), a Fusarium mycotoxin, is suspected of inducing its anorectic/feed refusal activity through a serotoninergic (5HT) mechanism, possible via 5HT₂‐receptors. In this study the efficiency of cyproheptadine (CYP), a serotonin antagonist and known appetite stimulant, to attenuate the adverse effect of DON was investigated in mice. CYP was administered in the feed for two days before animals began receiving the DON, which was also added to the feed. Both agents were administered concurrently thereafter for a 12‐day period. Dosing levels included various combinations of the two compounds, ranging from 0–16 ppm DON and 0–20 ppm CYP.

Results showed that CYP could effectively offset the reduction in feed intake caused by dietary DON, but only when dose levels were optimized (CYP appeared to have a narrow effective dose range, which was also dependent on the DON concentration). In fact, optimum CYP doses were able to enhance feed intake in DON‐fed mice above control levels, indicating that more than just a direct block of the toxin's effect was occurring. Conversely though, the effect of CYP on weight gain (WG) was ambiguous. At the lower CYP doses (≤ 5 ppm), alone or in combination with the lowest DON level tested (4 ppm), a modest positive effect was noted, but at the higher DON concentrations (≥ 8 ppm) the overall WG generally remained depressed, and tended to be reduced further by increasing doses of CYP.

These results provide additional support that serotoninergic mechanisms probably play a role in mediating DON‐induced reduction in feed intake. Where and how DON actually initiates its anorectic effect, however, has not been resolved.     

The role of tryptophan in don‐induced feed rejection

Abstract

Deoxynivalenol (DON, vomitoxin) commonly produced by Fusarium fungi can alter feeding behaviour of pigs and other farm animals. The effects of dietary tryptophan (TRP, precursor of brain amine serotonin) in combination with DON were examined in mice to determine if TRP can modulate DON toxicity. Results indicated that brain TRP can be influenced by dietary TRP, but no evidence of TRP potentiating DON toxicity was observed. Higher TRP levels likely induced amino acid imbalance leading to weight gain suppression.     

Distribution of deoxynivalenol in cerebral spinal fluid following administration to swine and sheep 1

Abstract

Deoxynivalenol (DON) is one of the major mycotoxins produced by Fusarium fungi. In evaluating DON as a potent CNS (emetic, anorexic) agent, its cerebral spinal fluid (CSF) and plasma pharmacokinetics were studied in pigs, a species very sensitive to the effects of DON, and sheep, a more tolerant animal. After intravenous administration, DON was detected very rapidly (<2.5 min) in the CSF of both species, but whereas peak levels (t‐max) occurred at 5–10 min in sheep, in swine it was 30–60 min. It would appear that the very rapid and extensive tissue distribution of DON in swine (Vdγ = 1.13 1 kg^‐1) may be slowing the rate of diffusion of the toxin into the CSF compared to sheep (Vd_β = 0.19 1 kg^‐1) where the toxin is confined essentially to the extracellular compartment. Area under curve calculations indicate approximately 2 1/2 times the amount of toxin eventually reaches the pig CSF compared to sheep CSF.

A good relationship between blood‐CSF DON levels was apparent in both species, although limitations in detection methods made it impossible to resolve a slow terminal phase (γ) in swine CSF which was evident in the plasma profile after iv administration.

Following oral administration of DON to pigs, a close correlation between plasma and CSF DON levels was observed. The toxin could be detected in CSF for up to 20 hr post‐dosing.     

Effect of the trichothecene deoxynivalenol on brain biogenic monoamines concentrations in rats and chickens

Male Sprague-Dawley rats (180 g) and 28-day-old Single Comb White Leghorn Cockerels (300 g) were orally dosed with deoxynivalenol (DON) at 2.5 mg kg-1 body weight. In the first experiment, whole brains were collected at 2, 6, 12, 24 and 48 hours after the toxin treatment and analyzed for brain biogenic monoamines by high-performance liquid chromatography with electrochemical detection. Although several interesting trends were observed, DON did not influence whole brain concentrations of monoamine neurotransmitters or their metabolites in either species, at any time. In a second experiment, brains were collected 24 hours postdosing, dissected into 5 brain regions (pons and medulla oblongata, cerebellum, hypothalamus, hippocampus and cerebral cortex), and analyzed. DON treatment resulted in significantly elevated concentrations of serotonin (HT) and 5-hydroxyindole-3-acetic acid (HIAA) in all brain regions of the rat. However, this was not seen in poultry, where DON treatment resulted in a decrease in norepinephrine (NE) in the hypothalamus and hippocampus, and a decrease in dopamine (DA) in the pons and medulla oblongata region. These results suggest that DON influences brain biogenic amine metabolism, and that there may be intraspecies differences in the central effects of this mycotoxin.     

Capsaicin-induced dysregulation of acid-base status in the American cockroach

Abstract

Members of TRP receptor family are involved in response to acidification. Here, we determined the effect of capsaicin, one of the TRP receptor activators, on hemolymph acid-base status in the American cockroach. Periplaneta americana adult individuals were injected with lactic acid (5% or 10%) and exposed to 100?µM capsaicin solution. Hemolymph pH was measured 15?min, 1, 4, 8 and 24?h after lactic acid and capsaicin application with a glass microelectrode. The results demonstrated that cockroaches recover from acidosis within 4?h from acid injection. Capsaicin impaired the buffering capacity of insects’ hemolymph, resulting in significant drop of hemolymph pH observed even 24?h after application. Joint action of capsaicin and acidosis reveals new insight into possible mechanism of capsaicin action on TRP receptors in insects.     

Delayed neurotoxicity of cyanofenphos in chickens

Abstract

Delayed neurotoxic ataxia, similar to that caused by neurotoxic organophosphorous compounds, has been shown to occur in hens after oral administration of Cyanofenphos (O‐ethyl‐O‐Cyanophenyl phenyl phosphonothionate) following either single or repeated oral doses. Axonal and myelin degeneration affecting the long tracts in spinal cord, peripheral nerves and medulla was demonstrated. The distal fibers with large diameters were particularly affected. This finding is a new contribution which has not been previously recorded. It implies that a thorough study of the structure‐activity relationships of phosphonothionates regarding their delayed neurotoxic effect is warranted.     

Investigation of the Ultraviolet Photolysis Method for the Determination of Organic Nitrogen in Aerosol Samples

Abstract

The research objective was to adapt the ultraviolet (UV)photolysis method to determine dissolved organic nitrogen (DON) in aqueous extracts of aerosol samples. DON was assumed to be the difference in total concentration of inorganic nitrogen forms before and after sample irradiation. Using a 2² factorial design the authors found that the optimal conversion of urea, amino acids (alanine, aspartic acid, glycine, and serine), and methylamine for a reactor temperature of 44 °C occurred at pH 2.0 with a 24-hr irradiance period at concentrations < µM of organic nitrogen. Different decomposition mechanisms were evident: the photolysis of amino acids and methylamine released mainly ammonium (NH₄ ⁺), but urea released a near equimolar ratio of NH₄ ⁺ and nitrate (NO₃ ^?). The method was applied to measure DON in the extracts of aerosol samples from Tampa, FL, over a 32-day sampling period. Average dissolved inorganic (DIN) and DON concentrations in the particulate matter fraction PM₁₀ were 78.1 ± 29.2 nmol-Nm^?3and 8.3 ± 4.9 nmol-Nm^?3, respectively. The ratio between DON and total dissolved nitrogen ([TDN] = DIN + DON) was 10.1 ± 5.7%, and the majority of the DON (79.1 ± 18.2%) was found in the fine particulate matter (PM_2.5) fraction. The average concentrations of DIN and DON in the PM_2.5 fraction were 54.4 ± 25.6 nmol-Nm^?3 and 6.5 ± 4.4 nmol-Nm^?3, respectively.     

Plasma pharmacokinetics of the mycotoxin deoxynivalenol following oral and intravenous administration to sheep

The pharmacokinetics of deoxynivalenol (DON) were studied in sheep after administrating intravenous and oral doses (0.5 and 5.0 mg/kg, respectively). The plasma concentrations were measured using an electron-capture gas chromatographic method. After iv administration DON plasma levels were found to decrease biexponentially, showing a rapid distribution phase (t 1/2 alpha = 12-23 min), followed by a slower elimination phase (t 1/2 beta = 57-78 min). Only trace levels of DON could be detected in plasma 7 hr post-dosing. Further pharmacokinetic data suggest that DON was confined mainly to extracellular fluid, and did not appear to undergo any significant binding or uptake by tissue. After oral dosing, DON was quickly absorbed (t-max 4.0-5.3 hr), but had a systemic bioavailability of only 7.5%; due in part to its rapid and efficient metabolism by rumen microorganisms. Half-life of elimination (t 1/2 beta) was 100-125 min following oral administration, and depending on the animal, required 20-30 hr to be cleared from the system. The metabolic formation of the glucuronide conjugate after iv and oral administration of DON appeared to occur quite efficiently (iv, 21%; oral, 75%), and its elimination half-lives (iv, 150-200 min; oral 6.1-7.1 hr) were considerably longer than that of the parent toxin. Detection in plasma of the de-epoxide metabolite, DOM-1, accounted for only a minor portion of the dose after either dosing regimen (iv, less than 2.0%; oral, less than 0.3%), occurring predominantly as the glucuronide conjugate.     

Effect of Isoflavones on Reproductive Performance,Testosterone Levels,Lipid Peroxidation,and Seminal Plasma Biochemistry of Male Rabbits

Abstract

The objective of this study was to determine the effect of either 2.5 mg/kg Body Weight or 5 mg/kg Body Weight (BW) doses of isoflavones on semen quality, testosterone levels, lipid peroxidation and semen biochemistry of male New Zealand White rabbits. Animals were given both 2.5 mg/kg BW and 5 mg/kg BW doses of isoflavones. The tested doses were given to rabbits orally every other day for 13 weeks. Treatment with isoflavones caused an increase (p < 0.05) in libido (by decreasing the reaction time), sperm concentration, sperm motility (%), total motile sperm per ejaculate (TMS), packed sperm volume (PSV), total functional sperm fraction (TFSF), total sperm output, initial fructose concentration and normal sperm, while dead sperm was reduced compared to control animals. On the other hand, ejaculate volume, initial hydrogen ion concentration (pH) and plasma testosterone levels did not change in treated animals with both doses of isoflavones as compared to control. Concentrations of thiobarbituric acid-reactive substances (TBARS), total lipids, and low density lipoprotein were significantly (p < 0.05) reduced in seminal plasma of rabbits treated with either 2.5 mg/kg BW or 5 mg/kg BW doses of isoflavones. While, the activities of glutathione S-transferase (GST), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), acid phosphatase (AcP), and alkaline phosphatase (AlP) were significantly (p < 0.05) increased in seminal plasma of treated animals. Also, total cholesterol, percentage cholesterol (out of total lipids), and high density lipoprotein were significantly (p < 0.05) increased, while triglyceride did not change in seminal plasma of treated animals. Supplementation at either level of isoflavones did not cause changes in live body weight (LBW), dry matter intake (DMI), and relative weights of testes and epididymis. The present results showed that either 2.5 mg/kg BW or 5 mg/kg BW doses of isoflavones caused an improvement of some semen characteristics and did not have negative effects on male fertility.     

Effect of quinalphos on blood enzymes and its acute toxicity in bubalus bubalis

Abstract

The acute toxic effects of quinalphos (0,0‐diethyl 0–2‐quinoxalyl phosphorothioata) uere investigated in male buffalo calves. Quinalphos was administered in single oral doses of 5, 7.5, 8.5 and 10 mg/kg body wt. and its effects on erythrocyte and plasma cholinesterases, serum aspartate aminotransferase and blood glucose were studied at various time intervals. The lowest dose (5 mg/kg) produced no apparent toxic symptoms. All the animals given highest dose (10 mg/kg) died within 60–82 hours after dosing. Quinalphos at all the dose levels markedly inhibited the erythrocyte and plasma cholinesterases (68–100%) and significantly elevated the levels of serum aspartate aminotransferase and blood glucose. Seven days after the administration of quinalphos, the blood cholinesterases in survivors remained inhibited to the extent of 41–77% whereas the levels of serum aspartate aminotransferase and blood glucose were comparable to control values.     

Hydroxyquinol Pathway for Microbial Degradation of Halogenated Aromatic Compounds

Several peripheral metabolic pathways can be used by microorganisms to degrade toxic aromatic compounds that are known to pollute the environment. Hydroxyquinol (1,2,4-trihydroxybenzene) is one of the central intermediates in the degradative pathway of a large variety of aromatic compounds. The present review describes the microorganisms involved in the degradative pathway, the key enzymes involved in the formation and splitting of the aromatic ring of (chloro)hydroxyquinol as well as the central intermediates formed. An attempt was also made to provide some estimation for genetic basis of the hydroxyquinol pathway.     

Application of a LC–MS/MS method for multi-mycotoxin analysis in infant formula and milk-based products for young children commercialized in Southern Brazil

ABSTRACT

An analytical method based on liquid chromatography–tandem mass spectrometry (LC–MS/MS) was validated and applied for the analysis of aflatoxin M₁ (AFM₁), ochratoxin A (OTA) and deoxynivalenol (DON) in infant formula and milk-based products for young children commercialized in Brazil. A total of 38 samples were evaluated, including 12 infant formula, 14 follow-on formula and 12 samples of milk-based products. AFM₁ was detected in 12 (32%) samples, and seven (18%) samples contained AFM₁ levels above the method limit of quantification in a concentration range between 0.013 and 0.067 ng mL^?1 (0.026 ± 0.019). Two samples of milk-based products exceeded the maximum level (ML) fixed by the European Union for AFM₁ in baby foods, however, all samples were in agreement with the levels established by the Brazilian regulation. OTA and DON were not detected in any of the analyzed samples.     

Microwave Plasma Conversion of Volatile Organic Compounds

Abstract

A microwave-induced, steam/Ar/O₂ , plasma “torch” was operated at atmospheric pressure to determine the feasibility of destroying volatile organic compounds (VOCs) of concern. The plasma process can be coupled with adsorbent technology by providing steam as the fluid carrier for desorbing the VOCs from an adsorbent. Hence, N₂ can be excluded by using a relatively inexpensive carrier gas, and thermal formation of oxides of nitrogen (NO_x ) is avoided in the plasma.

The objectives of the study were to evaluate the technical feasibility of destroying VOCs from gas streams by using a commercially available microwave plasma torch and to examine whether significant byproducts were produced. Trichloroethene (TCE) and toluene (TOL) were added as representative VOCs of interest to a flow that contained Ar as a carrier gas in addition to O₂ and steam.The O₂ was necessary to ensure that undesirable byproducts were not formed in the process. Microwave power applied at 500–600 W was found to be sufficient to achieve the destruction of the test compounds, down to the detection limits of the gas chromatograph that was used in the analysis. Samples of the postmicrowave gases were collected on sorbent tubes for the analysis of dioxins and other byproducts. No hazardous byproducts were detected when sufficient O₂ was added to the flow. The destruction efficiency at a fixed microwave power improved with the addition of steam to the flow that passed through the torch.     

The effect of deoxynivalenol on the secretion activity,proliferation and apoptosis of porcine ovarian granulosa cells in vitro

The aim of this in vitro study was to examine the secretion activity, markers of proliferation and apoptosis in porcine ovarian granulosa cells (GCs) after deoxynivalenol (DON) addition. Ovarian granulosa cells were incubated with DON for 24h: 10, 100 and 1000 ng/mL, while the control group received no DON. The secretion of insulin-like growth factor I (IGF–I) and progesterone was determined by radioimmunoassay (RIA) and expression of cyclin B1, PCNA and caspase-3 by immunocytochemistry. IGF–I release by GCs was inhibited by DON, while progesterone release and the expression of cyclin B1 was stimulated by DON (at 1000 ng/mL but not at 10 and 100 ng/mL). PCNA expression was stimulated by DON (at 100 and 1000 ng/mL but not at 10 ng/mL). Caspase-3 expression was not influenced by DON treatment (at all doses). In conclusion, our results indicate, (1) a direct effect of DON on secretion of growth factor IGF-I and steroid hormone progesterone, (2) expression of markers of proliferation (cyclin B1 and PCNA) but not on the (3) expression of marker of apoptosis (caspase-3) in porcine ovarian granulosa cells. This in vitro study suggests the dose-dependent association of DON on porcine ovarian functions.     

Decomposition of volatile organic compounds using gliding arc discharge plasma

ABSTRACT

This work provides a systematic review on the decomposition of volatile organic pollutants in flue gas through the gliding arc (GA) plasma technology. To begin with, the basic mechanisms of GA plasma generation are summarized and three characteristic stages existed during the GA plasma generation process are revealed: gas breakdown stage, equilibrium stage, and non-equilibrium stage. Then, the types of GA reactors are comparatively illustrated. Possible destruction mechanisms of volatile organic compounds (VOCs) by GA plasma are discussed by taking chloroform, benzene, and methanol as examples. Furthermore, the effects of many operating parameters on the VOCs destruction efficiency are comprehensively analyzed. Simultaneously, the product distribution, energy cost, technical and economic during the whole decomposition process are considered. Finally, the advantages and disadvantages of GA plasma and its further development trend are concluded from the academic and industrial application of GA plasma in VOCs decomposition.

Implications: This paper comprehensively describes the principle, characteristics, research progress and engineering application examples of the degradation of volatile organics by gliding arc discharge plasma, so that readers can fully understand the degradation of volatile organics by gliding arc discharge plasma and provide theoretical basis for the industrial application of the degradation of volatile organics by gliding arc discharge plasma.     

Determination of T‐2 toxin in grain and grain products by HPLC and TLC

Abstract

The purpose of this study was to investigate the T‐2 toxin contaminated grain and grain products consumed especially by Turkish population. The T‐2 toxin was detected using the high performance liquid chromatography (HPLC) with UV detector at 208 nm and the identify of T‐2 was further confirmed by thin layer chromatography (TLC). The recovery was 91 ±4.24% for corn flour fortified with the known amount of T‐2 toxin (1 ppm). The detection limits of T‐2 toxin for the HPLC and the TLC were 25 ng and 50 ng, respectively. A total of 30 commercially available grain and grain product samples were analyzed. Two corn flour samples were found to contain detectable levels of T‐2 toxin at a level of 1.60 ppm and 4.08 ppm.     

Metabolic fate and elimination in milk, urine and bile of deoxynivalenol following administration to lactating sheep

Using a combination of radioisotopic counting and chromatographic detection techniques, the kinetics and metabolic fate of deoxynivalenol (DON) in plasma, urine and bile were studied in lactating sheep, as was the transmission of residues to milk. Following intravenous administration, the plasma clearance of 14C-DON-derived radioactivity was rapid and followed a tri-phasic decay curve comprised of a bi-exponential decrease in DON (rapid distribution phase, t1/2 alpha = 16.2 min; slower elimination phase t1/2 beta = 66.5 min) and the formation and elimination (t1/2 beta = 188.0 min) of its major plasma metabolite, DON-glucuronide conjugate, which accounted for 13% of the plasma radioactivity levels. DON was rapidly cleared from the body by metabolism to 7 possible metabolites, which were excreted essentially in the urine (91%) and to a lesser extent in the bile (6%). Most (67%) of the recovered radioactivity was in the form of the glucuronide conjugates of DON (54%) and the de-epoxide metabolite, DOM-1 (13%). Excretion of unmetabolized DON accounted for 11%. The remaining recovered dose (18%) comprised of minor amounts of DOM-1 (6%), DON-sulfate conjugate (2%) and 3 unidentified radioactive components (10%). Studies on the presence of DON-derived residues in milk indicated that, relative to the dose, only trace amounts were transmitted following either oral or iv administration of the toxin.     

Chemistry of fog waters in California's Central Valley—Part 3: concentrations and speciation of organic and inorganic nitrogen

Although organic nitrogen (ON) has been found to be a ubiquitous and significant component in wet and dry deposition, almost nothing is known about its concentration or composition in fog waters. To address this gap, we have investigated the concentration and composition of ON in fog waters collected in Davis, in California's Central Valley. Significant quantities of dissolved organic nitrogen (DON) were found in these samples, with a median concentration of 303 μM N (range=120–1630 μM N). DON typically represented approximately 16% of the total dissolved nitrogen (inorganic+organic) in Davis fog waters. The median concentration of nitrogen in free amino acids and alkyl amines was 16 μM N (range=3.8–120 μM N), which accounted for 3.4% of the DON in Davis fogs. Thus, although the absolute concentrations of free amino compounds were significant, they were only a minor component of the DON pool. Combined amino nitrogen (e.g., proteins and peptides) was present at higher concentrations and accounted for 6.1–29% (median=16%) of DON. Overall, free and combined amino compounds typically accounted for a median value of 22% of DON in the fog waters.The high concentrations of DON found, and the fact that amino and other N-containing organic compounds can serve as nitrogen sources for microorganisms and plants, indicate that atmospheric ON compounds likely play an important role in nitrogen cycling in the Central Valley. In addition, due to the basicity of some N functional groups, ON compounds likely contribute to the previously observed acid buffering capacity of Central Valley fog waters. Finally, a comparison of fog waters with fine particles (PM_2.5) collected from the same site during the same period of time indicated that the median concentrations (mol N m⁻³-air) of total water-soluble ON, free amino nitrogen and total amino nitrogen were very similar in the fog water and PM_2.5. Given the high water solubility of many organic N compounds, this result suggests that ON might contribute to the hygroscopic properties of atmospheric particles.     

Evaluation of cationic polyacrylamide-based hybrid coagulation for the removal of dissolved organic nitrogen

Dissolved organic nitrogen (DON) is an important component of aquatic environment of which amount impacts water quality. Thus, removal of DON has attracted wide attention. At present, it is difficult for common coagulation to remove DON from the aquatic environment. The cationic polymers can help to improve the removal efficiency of DON to some extent, but the underlying mechanism of the ascension is not clear. In order to grasp its removal behavior and further improve the removal efficiency of DON in the future, we evaluated the effect of a hybridized coagulant of polyacrylamide with iron-based coagulant on removal of aquatic DON. A higher floc growth rate (119.82 μm/min) and recovery factors (26.96) were found in the hybrid coagulation. The parameters affecting the DON and the dissolved organic carbon (DOC) included the molar ratio of Zn to Fe (n_Zn/n_Fe), CPAM content, and molar ratio of OH to Fe (n_OH/n_Fe): n_Zn/n_Fe had a larger influence in DON removal than CPAM content; CPAM had a larger influence in the DOC removal; n_OH/n_Fe played a moderate effect between CPAM and n_Zn/n_Fe. Mutual effect of hybrid coagulants indicated the colloidal species to be helpful in enhancing DOC and DON removal. Other parameters affecting coagulation performance included the pH: the estimated maximum DON removal efficiency occurred at pH 6, DOC removal efficiency at pH 8. The above results found in this study showed that DON removal was affected by the ingredient and the species composition of the hybrid coagulant, and the water environmental parameter. The enhanced efficiency of DON removal in the presence of CPAM was mainly attributed to the increased adsorption-bridging and sweep-floc.