High Sensitivity of Aged Mice to Deoxynivalenol  (Vomitoxin)-Induced Anorexia Corresponds to Elevated Proinflammatory Cytokine and Satiety Hormone Responses

Clark, Erica; Flannery, Brenna M.; Gardner, Elizabeth M.; Pestka, James J.

doi:10.3390/toxins7104199

Cited by 19 publications

(14 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Key adjustments to increase sensitivity included dilution of enzyme conjugate, increased incubation time and inclusion of after-market DON standards ranging from 1 to 200 ng/mL. DON was reported as DON equivalents because this ELISA was 100% cross-reactive with DON-3-GlcA, the major glucuronide DON metabolite in the mouse [ 35 ]. Cross-reactivity with other DON glucuronides was not determined because of lack of available standards.…”

Section: Methodsmentioning

confidence: 99%

Sex Is a Determinant for Deoxynivalenol Metabolism and Elimination in the Mouse

Pestka

Clark

Schwartz-Zimmermann

et al. 2017

Toxins

Self Cite

View full text Add to dashboard Cite

Based on prior observations that deoxynivalenol (DON) toxicity is sex-dependent, we compared metabolism and clearance of this toxin in male and female mice. Following intraperitoneal challenge with 1 mg/kg bw DON, the dose used in the aforementioned toxicity study, ELISA and LC–MS/MS analyses revealed that by 24 h, most DON and DON metabolites were excreted via urine (49–86%) as compared to feces (1.2–8.3%). Females excreted DON and its principal metabolites (DON-3-, DON-8,15 hemiketal-8-, and iso-DON-8-glucuronides) in urine more rapidly than males. Metabolite concentrations were typically 2 to 4 times higher in the livers and kidneys of males than females from 1 to 4 h after dosing. Trace levels of DON-3-sulfate and DON-15-sulfate were found in urine, liver and kidneys from females but not males. Fecal excretion of DON and DON sulfonates was approximately 2-fold greater in males than females. Finally, decreased DON clearance rates in males could not be explained by glucuronidation activities in liver and kidney microsomes. To summarize, increased sensitivity of male mice to DON’s toxic effects as compared to females corresponds to decreased ability to clear the toxin via urine but did not appear to result from differences in toxin metabolism.

show abstract

Section: Methodsmentioning

confidence: 99%

Sex Is a Determinant for Deoxynivalenol Metabolism and Elimination in the Mouse

Pestka

Clark

Schwartz-Zimmermann

et al. 2017

Toxins

Self Cite

View full text Add to dashboard Cite

show abstract

“…The mycotoxins doses were selected based on previously published research 30 , 31 . Briefly, 2 mg/kg DON, 20 mg/kg ZEN and the mixture of DON and ZEN (2 mg/kg DON, 20 mg/kg ZEN), were implemented to mice through intragastrical administration for three weeks, referring to the duration in sub-chronic toxicity test 32 , as well as the change of physical and chemical indicators in mice.…”

Section: Discussionmentioning

confidence: 99%

Explaining combinatorial effects of mycotoxins Deoxynivalenol and Zearalenone in mice with urinary metabolomic profiling

Zhu

Blaženović

et al. 2018

Sci Rep

View full text Add to dashboard Cite

Urine metabolic profiling of mice was conducted utilizing gas chromatography-mass spectrometry (GC-MS) to investigate the combinatory effect of mycotoxins deoxynivalenol (DON) and zearalenone (ZEN) on the metabolism of the mice. Experiments were conducted by means of five-week-old mice which were individually exposed to 2 mg/kg DON, 20 mg/kg ZEN and the mixture of DON and ZEN (2 mg/kg and 20 mg/kg, respectively). The intragastric administration was applied for three weeks and urine samples were collected for metabolic analysis. Univariate and multivariate analysis were applied to data matrix processing along with respective pathway analysis by MetaMapp and CytoScape. The results showed that the combined DON and ZEN administration resulted in lower significant changes, compared to the individual mycotoxin treated groups verified by heatmap. Metabolic pathways network mapping indicated that the combined mycotoxins treated groups showed a little effect on the metabolites in most pathways, especially in glucose metabolism and its downstream amino acid metabolism. In glucose metabolism, the content of galactose, mannitol, galactonic acid, myo-inositol, tagatose was drastically down-regulated. Furthermore, the organic acids, pyruvate, and amino acids metabolism displayed the same phenomenon. In conclusion, the combined DON/ZEN administration might lead to an “antagonistic effect” in mice metabolism.

show abstract

“…Gut satiety hormones are well-characterized in anorexia induction by trichothecenes. DON could elevate the levels of gut satiety hormones in the plasma, including cholecystokinin (CCK), peptide YY 3-36 (PYY 3-36 ), glucagon-like peptide-1 (GLP-1), and glucose dependent insulinotropic polypeptide (GIP) in mice [ 39 , 40 , 41 , 42 ]. Inhibiting the receptors of these hormones could attenuate DON-induced anorexia, suggesting that these hormones are involved in DON-induced anorexia.…”

Section: Discussionmentioning

confidence: 99%

“…Trichothecenes are well known to upregulate the expression of pro-inflammatory cytokines, including interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) [ 39 ]. Such a cytokine storm could cause sickness, with anorexia as a hallmark [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Comparison of Anorectic Potencies of Type A Trichothecenes T-2 Toxin, HT-2 Toxin, Diacetoxyscirpenol, and Neosolaniol

Zhang

Liu³

et al. 2018

Toxins

View full text Add to dashboard Cite

Trichothecene mycotoxins are common contaminants in cereal grains and negatively impact human and animal health. Although anorexia is a common hallmark of type B trichothecenes-induced toxicity, less is known about the anorectic potencies of type A trichothecenes. The purpose of this study was to compare the anorectic potencies of four type A trichothecenes (T-2 toxin (T-2), HT-2 toxin (HT-2), diacetoxyscirpenol (DAS), and neosolaniol (NEO)) in mice. Following oral exposure to T-2, HT-2, DAS, and NEO, the no observed adverse effect levels (NOAELs) and lowest observed adverse effect levels (LOAELs) were 0.01, 0.01, 0.1, and 0.01 mg/kg body weight (BW), and 0.1, 0.1, 0.5, and 0.1 mg/kg BW, respectively. Following intraperitoneal (IP) exposure to T-2, HT-2, DAS, and NEO, the NOAELs were 0.01 mg/kg BW, except for DAS (less than 0.01 mg/kg BW), and the LOAELs were 0.1, 0.1, 0.01, and 0.1 mg/kg BW, respectively. Taken together, the results suggest that (1) type A trichothecenes could dose-dependently elicit anorectic responses following both oral gavage and IP exposure in mice; (2) the anorectic responses follow an approximate rank order of T-2 = HT-2 = NEO > DAS for oral exposure, and DAS > T-2 = HT-2 = NEO for IP administration; (3) IP exposure to T-2, HT-2, DAS, and NEO evoked stronger anorectic effects than oral exposure. From a public health perspective, comparative anorectic potency data should be useful for establishing toxic equivalency factors for type A trichothecenes.

show abstract

High Sensitivity of Aged Mice to Deoxynivalenol (Vomitoxin)-Induced Anorexia Corresponds to Elevated Proinflammatory Cytokine and Satiety Hormone Responses

Cited by 19 publications

References 46 publications

Sex Is a Determinant for Deoxynivalenol Metabolism and Elimination in the Mouse

Sex Is a Determinant for Deoxynivalenol Metabolism and Elimination in the Mouse

Explaining combinatorial effects of mycotoxins Deoxynivalenol and Zearalenone in mice with urinary metabolomic profiling

Comparison of Anorectic Potencies of Type A Trichothecenes T-2 Toxin, HT-2 Toxin, Diacetoxyscirpenol, and Neosolaniol

Contact Info

Product

Resources

About