The Toxicokinetics, Excretion Patterns, and Milk Transmission of Ochratoxin A in Lactating Sows.

Ochratoxin A (OTA), a mycotoxin commonly found in feedstuffs, is known for its detrimental effects on the kidneys and liver, posing significant health risks to animals and humans. This study investigated the toxicokinetics, excretion patterns, and milk transmission of Ochratoxin A (OTA) in lactating sows. The sows were administered a single oral dose of 500 µg/kg BW (body weight), followed by the systematic sampling of plasma, feces, urine, and milk. Plasma samples were collected at 0, 5, 15, and 30 min, and 1, 2, 3, 6, 9, 12, 24, 48, 72, 88, 96, and 120 h post administration. Feces samples were collected at 6 h intervals for the first 12 h, then at 12 h intervals until 120 h, while urine samples were collected at 6 h intervals up to 120 h. Milk samples were collected at 0, 6, 12, 24, 36, 48, 72, 96, and 120 h. The concentration of OTA and its primary metabolite OTα were quantitatively analyzed using ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The results revealed that the peak plasma concentrations of OTA (920.25 ± 88.46 µg/L) were observed at 9 h following administration. The terminal elimination half-life was recorded at 78.47 ± 7.68 h, with a volume of distribution of 0.16 ± 0.003 L/kg. Moreover, this study documented the excretion of OTA and OTα across a span of 120 h, revealing that feces and urine accounted for 18.70 ± 0.04% and 8.40 ± 0.002% of the total intake amounts, respectively (calculated based on substance amounts). Furthermore, this experiment detected OTA residues in the milk of lactating sows, with the milk-to-plasma (M/P) ratio initially increasing from 0.06 to 0.46 within the first 24 h following OTA ingestion. These findings offer an exhaustive temporal analysis of OTA's toxicokinetics in lactating sows, emphasizing its pervasive distribution and elimination through various bodily excreta.

Toxicokinetics of Zearalenone following Oral Administration in Female Dezhou Donkeys.

Zearalenone (ZEN) is a mycotoxin produced by various Fusarium strains, that is present in food and feed raw materials worldwide, causing toxicity effects in animals and humans. This research aimed to explore the toxicokinetics of ZEN on female Dezhou donkeys following a single oral exposure dosage of 2 mg/kg BW (body weight). The sample collection of donkeys plasma was carried out at 0, 5, 10, 15, 20, 30, 45, 60, 90 min, 2 h, 2.5 h, 3 h, 3.5 h, 4 h, 4.5 h, 6 h, 9 h, 12 h, 24 h, 48 h, 72 h, 96 h and 120 h via intravenous catheter, and fecal and urinary samples were severally collected at 0 h and every 6 h until 120 h. The concentrations of ZEN, α-zearalenol (α-ZOL), ß-zearalenol (ß-ZOL), α-zearalanol (α-ZAL), ß-zearalanol (ß-ZAL), zearalanone (ZAN) in plasma, urine, and feces were detected by UPLC-MS/MS. Only ZEN was detected in plasma, and the maximum was 15.34 ± 5.12 µg/L occurred at 0.48 h after gavage. The total plasma clearance (Cl) of ZEN was 95.20 ± 8.01 L·kg·BW-1·h-1. In addition, the volume of distribution (Vd) was up to 216.17 ± 58.71 L/kg. The percentage of total ZEN (ZEN plus the main metabolites) excretion in feces and urine was 2.49% and 2.10%, respectively. In summary, ZEN was fast absorbed and relatively slowly excreted in female donkeys during 120 h after a single gavage, indicating a trend of wider tissue distribution and longer tissue persistence.

Toxicokinetics of Deoxynivalenol in Dezhou Male Donkeys after Oral Administration.

Deoxynivalenol (DON) is detected in different types of foods and feeds, inducing toxicity in humans and animals. After entering the organism, DON first appears in the plasma; then, it is rapidly absorbed and distributed in various organs and tends to accumulate in the body to exert its toxic effects. This study was performed to investigate the toxicokinetics of DON on Dezhou male donkeys after a single oral dose of 500 µg/kg·BW (body weight). The plasma of donkeys was collected at 0, 5, 10, 15, 20, 30, 45 min, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 6, 9, 12, 24, 48, 72, 96 and 120 h after administration, and the feces and urine were collected at 0 h and at 6 h intervals up to 24 h, followed by 4 h intervals up to 120 h. The concentrations of DON in plasma, urine and feces were determined by HPLC. The peak concentration of DON in plasma was 174.30 µg/L, which occurred at 1.07 h after oral gavage. The recovery of unchanged DON in urine and feces amounted to 19.98% and 6.74%, respectively. Overall, DON was rapidly absorbed and slowly eliminated in donkeys within 120 h following a single oral dose, which can lead to DON accumulation in the body if ingested for a long time.

Toxicokinetics of a Single Oral Dose of OTA on Dezhou Male Donkeys.

Ochratoxin (OTA) is widely present in a wide range of foods and feeds, causing adverse effects on animals and humans. This study aims to explore the toxicokinetics of OTA-contaminated materials on the Dezhou male donkey. Donkeys received a single orally dose of 2500 µg OTA/kg BW, obtained from Aspergillus ochraceus culture material. The concentrations of OTA in plasma collected at 0, 5, 10, 15, 20, 30, 45 min, and at 1, 1.5, 2, 3, 6, 9, 12, 24, 48, 72, 96 and 120 h were detected by HPLC. OTA eliminated in urine and feces were quantified at 6-h intervals up to 24 h and then at 4-h intervals up to 120 h. The results suggested that the maximum concentration of OTA in plasma was observed at 12 h after administration, with a mean value of 10.34 µg/mL. The total excretion in both urine and feces was about 10% of the intake until 120 h.

Pharmacokinetics of florfenicol and its metabolite florfenicol amine in the plasma, urine, and feces of fattening male donkeys following single oral administration.

Florfenicol (FF) is a commonly used antibacterial agent in animals. We investigated the pharmacokinetics of FF and its metabolite florfenicol amine (FFA) in donkeys. Donkeys were administered FF (30 mg/kg bodyweight, p.o.). Pharmacokinetic parameters were calculated using a non-compartmental model. The FF (FFA) pharmacokinetics parameters were characterized by along elimination half-life (t1/2 kz) of 5.92 h (15.95 h), plasma peak concentration (Cmax) of 0.13 µg/mL (0.08 µg/mL), and the time taken to reach Cmax (Tmax) of 0.68 h (0.72 h). The area under plasma concentration-time curve and mean residence time of FF (FFA) in plasma were 1.31 µg·mL-1·h (0.47 µg·mL-1·h) and 10.37 h (18.40 h), respectively. The t1/2 kz of FF and FFA in urine was 21.93 and 40.26 h, and the maximum excretion rate was 10.56 and 4.03 µg/h reached at 25.60 and 32.20 h, respectively. The respective values in feces were 0.02 and 0.01 µg·h-1 reached at 33.40 h. The amount of FF and FFA recovered in feces was 0.52 and 0.22 µg, respectively. In conclusion, FF (FFA) is rapidly absorbed and slowly eliminated after a single oral administration to donkeys. Compared to FF, FFA was more slowly eliminated. FF (FFA) is mostly excreted through urine.

Effects of maternal T-2 toxin exposure on microorganisms and intestinal barrier function in young mice.

T-2 toxin belongs to the trichothecenes group A compound, mainly produced by Fusarium fungi. It has been shown that T-2 toxin could cross the placental barrier and breast milk, thus endangering the health of offspring. The present study aimed to explore the effects of maternal T-2 toxin exposure on the integrity of the intestinal barrier and the intestinal microflora of young mice. From late pregnancy (GD 14) to lactation (LD 21), pregnant mice were given T-2 toxin daily at 0, 0.005, or 0.05 mg T-2 toxin/kg BW. Postnatal day 21 (PND21), PND28, and PND56 young mice were chosen as objects to detect the influences of maternal T-2 toxin exposure to mice on the offspring. The results showed that maternal exposure to T-2 toxin disturbed the balance of the intestinal microbial flora of the young mice. Villous adhesions and fusion of ileum were observed in T-2-treated groups. In addition, supplementation of T-2 toxin significantly decreased the gene expressions of Claudin 1, Occludin, Tjp1, Il10, Il6, and Tnf in PND 21. However, in PND 28, the expressions of Tnf were significantly increased. The expressions of Claudin 1, Occludin, Tjp1, Il10, Il6 and Tnf were significantly increased after T-2 toxin treatment in PND 56. These results suggested that maternal exposure to T-2 toxin has negative influences on the intestine of young mice, which may be due to the alterations of microbial composition.

Dietary selenium sources alleviate immune challenge induced by Salmonella Enteritidis potentially through improving the host immune response and gut microbiota in laying hens.

The aim of this study was to evaluate the effects of different selenium (Se) sources on the immune responses and gut microbiota of laying hens challenged with Salmonella enteritidis (S. Enteritidis). A total of 240 45-week-old layers were randomly divided into eight groups with six replicates per group according to a 4 × 2 factorial design, including a blank diet without Se supplementation (CON group) and three diets with 0.3 mg/kg Se supplementation from sodium selenite (IS group), yeast Se (YS group), and selenium-enriched yeast culture (SYC group), respectively. After 8 weeks of feeding, half of them were orally challenged with 1.0 ml suspension of 109 colony-forming units per milliliter of S. Enteritidis daily for 3 days. The serum was collected on days 3, 7, and 14, and the cecum content was collected on day 14 after challenge. There was no significant difference in laying performance among the eight groups before challenge. The S. Enteritidis challenge significantly decreased the laying performance, egg quality, GSH-Px, IgG, and IgM and increased the ratio of feed and egg, malondialdehyde (MDA), Salmonella-specific antibody (SA) titers, IL-6, IL-2, IL-1ß, and INF-γ. However, SYC increased the level of GSH-Px and IgG and decreased IL-6, while YS decreased the level of IL-2 and IL-1ß. What is more, Se supplementation decreased the SA titers to varying degrees and reduced the inflammatory cell infiltration in the lamina propria caused by S. Enteritidis infection. In addition, the S. Enteritidis challenge disrupted the intestinal flora balance by reducing the abundance of the genera Clostridium innocuum, Lachnospiraceae, and Bifidobacterium and increasing the genera Butyricimonas and Brachyspira, while Se supplementation increased the gut microbial alpha diversity whether challenged or not. Under the S. Enteritidis challenge condition, the alteration of microbial composition by the administration of different Se sources mainly manifested as IS increased the relative abundance of the genera Lachnospiraceae and Christensenellaceae, YS increased the relative abundance of the genera Megamonas and Sphingomonas, and SYC increased the genera Fusobacterium and Lactococcus. The alteration of gut microbial composition had a close relationship with antioxidant or immune response. To summarize, different Se sources can improve the egg quality of layers challenged by S. Enteritidis that involves elevating the immunity level and regulating the intestinal microbiota.

Effects of Different Selenium Sources on the Laying Performance, Egg Quality, Antioxidant, and Immune Responses of Laying Hens under Normal and Cyclic High Temperatures.

The aim of this study was to evaluate the effects of different selenium (Se) sources on the laying performance, egg quality, antioxidant, and immune responses of laying hens under different temperatures. In an 8-week experiment, a total of 480 44-week-old laying hens were randomly divided into 8 groups, with 6 replicates for each group and 10 hens per replicate, and fed with a basal diet (BK), basal diet with 0.3 mg/kg of Se from sodium selenite (SS), from Se yeast (SY), or from selenium-enriched yeast culture (SYC) under normal temperature (NT, 26 ± 2 °C) and cyclic high temperature (CHT, 26 ± 2 °C~33 ± 2 °C). CHT decreased the laying performance and serum levels of Se, immunoglobulin G (IgG), and interleukin-10 (IL-10), and significantly increased the serum free triiodothyronine (FT3), deiodinase-I (DI-I), and heat stress protein (HSPs) (p < 0.05). In addition, SYC increased the egg yolk color, and SS increased serum IgG level. SS, SY, and SYC reduced the level of interleukin-6 (IL-6) (p < 0.05). In conclusion, Se can increase egg yolk color, antioxidant capacity, and immune capacity under heat stress, and the effect of organic Se is better than that of inorganic Se.

Effects of maternal T-2 toxin exposure on the hepatic glycolipid metabolism in young mice.

T-2 toxin is a kind of group A trichothecenes mycotoxins, frequently detected in various foods and feeds, having high toxic effects on both humans and animals. The present study aims to investigate the toxic effects of T-2 toxin exposure to ICR mice during pregnancy and lactation on liver glycolipid metabolism of young mice. The pregnant mice were given 0, 0.005 and 0.05 mg of T-2 toxin/kg bw daily through oral gavage from late gestation (GD 14) to the lactation (LD 21). Liver and serum samples of the young mice were collected on postnatal day 21 (PND 21), PND 28 and PND 56. The results showed that T-2 toxin increased the contents of triglycerides (TG), total cholesterol (T-CHO) and glucose in serum of young mice on PND 21 and PND 28. In addition, obvious lipid droplets of liver in T-2 toxin treatment groups were observed, especially in 0.05 mg group of PND 21and PND 28. Compared with the control group, T-2 treatment also increased the expressions of genes associated with liver glycolipid metabolism, such as PEPCK, Glut2, Fas, Acox1, Hmgcr, PPARα, Srebp1 and CD36. These results demonstrated T-2 toxin exposure to pregnant mice could cause liver glycolipid metabolism disruption in the young mice and the toxic effects weakened on PND 56.

Disruption of cytochrome P450 enzymes in the liver and small intestine in chicken embryos in ovo exposed to glyphosate.

Glyphosate is the active component of several commercial formulations as in Roundup®. The present study was investigated the toxic effects of pure glyphosate or Roundup® on the liver and small intestine of chick embryos. On day 6, a total of 180 fertile eggs injected with deionized water (control group), 10 mg pure glyphosate, or 10 mg of the active ingredient glyphosate in Roundup®/kg egg mass. The results showed an increase in relative weights of the liver in embryos that treated with Roundup®. Furthermore, oxidative stress was observed in the embryos treated with glyphosate or Roundup®, increased total superoxide dismutase, and content of malondialdehyde in the liver and intestine; moreover, decrease of glutathione peroxidase in the liver with increased in the intestine compared with the control. Besides, glutamic-pyruvic transaminase was increased in Roundup® group compared with other groups. Moreover, histopathological alterations in the liver and intestine tissues were observed in treated groups. Suppression of hepatic CYP1A2, CYP1A4, CYP1B1, and MDR1 mRNA expression after exposed to Roundup®. Furthermore, inhibition of CYP1A4 in the duodenum, CYP1A4, and MRP2 in the jejunum in embryos exposed to glyphosate or Roundup®. In addition, glyphosate treatment caused an increase of CYP3A5, CYP1C1, and IFNY mRNA expression in the jejunum and CYP1A2 expression in the ileum, while IFN-Y gene increase in embryos treated with Roundup®. In conclusion, in ovo exposure to glyphosate caused histopathological alterations and induced oxidative stress in the liver and small intestines. Moreover, the expression of cytochrome P450, MDR1, and MRP2 transporters was also modulated in the liver and small intestines for chick embryos.

Deoxynivalenol induced apoptosis and inflammation of IPEC-J2 cells by promoting ROS production.

Deoxynivalenol (DON) frequently detected in a wide range of foods and feeds, inducing cytotoxicity to animals and humans. To investigate the underlying mechanism of DON-induced apoptosis and inflammation in porcine small intestinal epithelium, intestinal porcine epithelial cells (IPEC-J2 cells) were chosen as objects, and were treated by different concentrations (0 µg/mL, 0.2 µg/mL, 0.5 µg/mL, 1.0 µg/mL, 2.0 µg/mL, 4.0 µg/mL, 6.0 µg/mL) of DON. The results showed that DON induced cytotoxicity of IPEC-J2 cells in a dose-dependent manner, which is demonstrated by decreasing cell viability. Compared with the control group, DON treatment increased the expressions of genes associated with inflammation and apoptosis, such as interleukin-1 beta (IL-1ß), cyclooxgenase-2 (COX-2), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), caspase-3, caspase-8, caspase-9, and decreased the cell anti-oxidative status. Protein immunofluorescence showed increased expression of caspase-3, nuclear factor kB (NF-κB) and phosphorylated NF-κB in IPEC-J2 cells. DON increased the content of intracellular reactive oxygen species (ROS) of IPEC-J2 cells. N-Acetyl-L-cysteine (NAC), a commonly used antioxidant, blocked DON-induced ROS generation, alleviated the DON-induced apoptosis and inflammation. These results suggested that DON-induced impairment of IPEC-J2 cells is possibly due to increased ROS production, and expressions of genes and proteins associated with apoptosis and inflammation.