Immunochemical assessment of deoxynivalenol tissue distribution following oral exposure in the mouse

Abstract

Deoxynivalenol (DON or vomitoxin) is a trichothecene mycotoxin commonly found in cereal grains that adversely affects growth and immune function in experimental animals. A competitive enzyme-linked immunosorbent assay (ELISA) was used to monitor the kinetics of distribution and clearance of DON in tissues of young adult B6C3F1 male mice that were orally administered 25mg/kg bw of the toxin. DON was detectable from 5 min to 24h in plasma, liver, spleen and brain and from 5 min to 8h in heart and kidney. The highest DON plasma concentrations were observed within 5-15 min (12 microg/mL) after dosing. There was rapid clearance following two-compartment kinetics (t(1/2)alpha=20.4 min, t 1/2 beta=11.8h) with 5% and 2% maximum plasma DON concentrations remaining after 8 and 24h, respectively. DON distribution and clearance kinetics in other tissues were similar to that of plasma. At 5 min, DON concentrations in mug/g were 19.5+/-1.9 in liver, 7.6+/-0.5 in kidney, 7.3+/-0.8 in spleen, 6.8+/-0.9 in heart and 0.8+/-0.1 in the brain. DON recoveries in tissues by ELISA were comparable to a previous study that employed (3)H-DON and 25mg/kg bw DON dose. The ELISA was further applicable to the detection of DON in plasma of mice exposed to the toxin via diet. This approach provides a simple strategy that can be used to answer relevant questions in rodents of how dose, species, age, gender, genetic background and route/duration of exposure impact DON uptake and clearance.

The ribotoxin deoxynivalenol affects the viability and functions of glial cells

“…Importantly, some of these alterations, including glutamate uptake, microglial viability, and modulation of the neuroinflammation, are observed at very low doses of toxin (50-200 nM). Pestka et al (2008b) have elegantly shown in mice that after oral exposure the amount of DON able to cross the blood-brain barrier corresponds approximately to 10% of its blood concentration. Based on that study and on the actual provisional maximum tolerable daily intake (PMTDI) of DON fixed at 1 lg/kg of body weight that gives a maximum blood concentration of 14 lg/L or 47 nM, it could be extrapolated that the brain concentration of DON could reach 4.7 nM in human exposed to DON at its PMTDI.…”

“…Previous studies have demonstrated that satratoxins possess direct neurotoxic effects, resulting in neuronal cell death and neuroinflammation (Corps et al, 2010;Pestka et al, 2008a). Although studies have demonstrated that trichothecenes, including DON, could cross the blood-brain barrier, accumulate in the brain and cause neurologic disorders (Pestka et al, 2008b;Ravindran et al, 2011), no evaluations of their effect on astrocytes or microglia have been conducted. In the present study, we investigated the effect of the ribotoxin DON on the viability and functions of astrocytic and microglial cells of animal and human origin.…”

Analytical methods for determination of mycotoxins: A review

“…Other mycotoxins detected were zearalenone and AFT B1. In other work ELISA was used to monitor the kinetics of distribution and clearance of DON in tissues of young adult B6C3F1 male mice that were orally administered with toxin [180]. DON was detectable from 5 min to 24 h in plasma, liver, spleen and brain and from 5 min to 8 h in heart and kidney.…”

Body composition and hormonal effects following exposure to mycotoxin deoxynivalenol in the high‐fat diet‐induced obese mouse

“…Notably, there is a strong inverse relationship between food consumption and brain levels of serotonin (5-hydroxytryptamine, 5-HT), an important upstream regulator of aforementioned peptides [7]. Since DON is detectable in brain following oral administration [8], the toxin has the potential to interfere with normal appetite regulation. In support of this contention, exposure to DON at 2.5 mg/kg - bw significantly increases serotonin levels in cerebellum and hypothalamus in rats at 24 hr after administration [9, 10].…”