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

Erica Clark,Brenna Flannery,James Pestka,Elizabeth Gardner

doi:10.3390/toxins7104199

Abstract

Deoxynivalenol (DON), a trichothecene mycotoxin that commonly contaminates cereal grains, is a public health concern because of its adverse effects on the gastrointestinal and immune systems. The objective of this study was to compare effects of DON on anorectic responses in aged (22 mos) and adult (3 mos) mice. Aged mice showed increased feed refusal with both acute i.p. (1 mg/kg and 5 mg/kg) and dietary (1, 2.5, 10 ppm) DON exposure in comparison to adult mice. In addition to greater suppression of food intake from dietary DON exposure, aged mice also exhibited greater but transient body weight suppression. When aged mice were acutely exposed to 1 mg/kg bw DON i.p., aged mice displayed elevated DON and DON3GlcA tissue levels and delayed clearance in comparison with adult mice. Acute DON exposure also elicited higher proinflammatory cytokine and satiety hormone responses in the plasma of the aged group compared with the adult group. Increased susceptibility to DON-induced anorexia in aged mice relative to adult mice suggests that advanced life stage could be a critical component in accurate human risk assessments for DON and other trichothecenes.

Highlights

Deoxynivalenol (DON, vomitoxin), a trichothecene mycotoxin produced by the fungusFusarium graminearum, is a common cereal grain contaminant that is highly resistant to heat processing, leading to contamination of human and animal food [1]
The discovery that anorectic responses to DON are greater in old animals is critical because advanced age in humans leads to a phenomenon known as the “anorexia of aging” in which elderly individuals show unintended weight loss [9,12,13]
The results presented indicate that aged mice are more susceptible than their young adult counterparts to DON-induced anorexia following either acute i.p. or dietary DON exposure

Summary

Introduction

Deoxynivalenol (DON, vomitoxin), a trichothecene mycotoxin produced by the fungusFusarium graminearum, is a common cereal grain contaminant that is highly resistant to heat processing, leading to contamination of human and animal food [1]. Adverse effects of acute exposure to DON include anorexia, diarrhea, and vomiting in experimental animals [2]. Chronic DON exposure can lead to immunotoxic effects and growth retardation. Commonly used in experimental studies for DON risk assessment, are incapable of vomiting but exhibit feed refusal and body weight suppression following exposure to the toxin [3]. Previous studies have investigated sex differences and the susceptibility of young animals to DON-induced anorexia [4,5,6,7,8]; the effects of this toxin on aged animals are largely unaddressed. Studying the adverse effects of DON in advanced life stage animals is important because approximately

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