Evaluation of insulin-like growth factor acid-labile subunit as a potential biomarker of effect for deoxynivalenol-induced proinflammatory cytokine expression

Abstract

Consumption of the trichothecene deoxynivalenol (DON) suppresses growth in experimental animals - an adverse effect that was used to establish the tolerable daily intake for this toxin. DON ingestion has been recently found to suppress plasma insulin-like growth factor acid-labile subunit (IGFALS), a protein essential for growth. Studies were conducted to explore the feasibility of using plasma IGFALS as a biomarker of effect for DON. In the first study, weanling mice were fed 0, 1, 2.5, 5 and 10 ppm DON and weight and plasma IGFALS determined at intervals over 9 wk. Reduced body weight gains were detectable beginning at wk 5 in the 10 ppm dose and wk 7 at the 5 ppm dose. Plasma IGFALS was significantly depressed at wk 5 in the 5 and 10 ppm groups at wk 9 in the 10 ppm group. Depressed IGFALS significantly correlated with reduced body weight at wk 5 and 9. Benchmark dose modeling revealed the BMDL and BMD for plasma IGFALS reduction were 1.1 and 3.0 ppm DON and for weight reduction were 2.1 and 4.5 ppm DON. In the second study, it was demonstrated that mice fed 15 ppm DON diet had significantly less plasma IGFALS than mice fed identical amounts of control diet. Thus DON’s influence on IGFALS likely reflects the combined effects of reduced food intake as well as its physiological action involving suppressors of cytokine signaling. Taken together, these findings suggest that plasma IGFALS might be a useful biomarker for DON’s adverse effects on growth.

Effects and biotransformation of the mycotoxin deoxynivalenol in growing pigs fed with naturally contaminated pelleted grains with and without the addition of Coriobacteriaceum DSM 11798

“…Some studies have shown that DON can cross the blood-brain barrier, leading to activation of central structures and affecting glial cell viability and function (Behrens et al 2015;Razafimanjato et al 2011). Other experiments have suggested a DONinduced reduction in plasma insulin-like growth factor acid-labile subunit (IGFALS) (Flannery et al 2013) and an increased pro-inflammatory cytokine expression (Pestka and Amuzie 2008), effects that initiate anorexia and poor growth performance. In addition, it has been reported that acute ipexposure of mice to DON (1-5 mg kg -1 ) may elevate levels of the gut satiety hormones peptide YY (PYY) and cholecystokinin (CCK) and that this may be related to DON-induced feed refusal and growth suppression (Flannery et al 2012).…”

Risks to human and animal health related to the presence of deoxynivalenol and its acetylated and modified forms in food and feed

“…A few studies have been published on a biomarker of effect for DON (Hopton et al., ; Amuzie and Pestka, ; Flannery et al., ) but because this area is still under development no studies on humans were identified.…”

Nitric oxide mediates apoptosis and mitochondrial dysfunction and plays a role in growth hormone deficiency by nivalenol in GH3 cells

“…Previous results from our laboratory found that both T-2 toxin and DON had an inhibitory effect on the GH gene expression and GH secretion in GH3 cells 12 . DON was reported to perturb the GH axis by suppressing two relevant growth-related proteins, IGF-1 and IGF-ALS, to induce growth retardation 9 , 51 . Pro-inflammatory cytokine expression was suggested to affect growth through the induction of several SOCSs in the mice exposed to DON 52 .…”