Dietary aflatoxin-induced stunting in a novel rat model: evidence for toxin-induced liver injury and hepatic growth hormone resistance

Abstract

Background Despite a strong statistical correlation between dietary aflatoxin B1 (AFB1)-exposure and childhood stunting, the causal mechanism remains speculative. This issue is important because of emerging interest in reduction of human aflatoxin exposure to diminish the prevalence and complications of stunting. Pediatric liver diseases cause growth impairment, and AFB1 is hepatotoxic. Thus, liver injury might mediate AFB1-associated growth impairment. We have developed a rat model of dietary AFB1-induced stunting to investigate these questions. Methods Newly-weaned rats were given AFB1-supplemented- or control-diets from age 3-9 weeks, and then euthanized for serum- and tissue-collection. Food intake and weight were serially assessed, with tibial-length determined at the experimental endpoint. Serum AFB1-adducts, hepatic gene and protein expression, and liver injury markers were quantified using established methodologies. Results AFB1-albumin adducts correlated with dietary toxin contamination, but such contamination did not affect food consumption. AFB1-exposed animals exhibited dose-dependent wasting and stunting, liver pathology, and suppression of hepatic targets of growth hormone (GH) signaling, but did not display increased mortality. Conclusion These data establish toxin-dependent liver injury and hepatic GH-resistance as candidate mechanisms by which AFB1-exposure causes growth impairment in this mammalian model. Interrogation of modifiers of stunting using this model could guide interventions in at-risk and affected children.

The Binding Efficiency and Interaction of Lactobacillus casei Shirota Toward Aflatoxin B1

“…The ability is owed to the expression of CYPs by the intestinal epithelial cells. Exposure to dietary AFB1 has been associated with weight loss and environmental enteropathy such as histological changes in the small intestine includes abnormal growth and inflamed intestinal cells ( Knipstein et al, 2015 ). Several studies have evaluated the toxicity of AFB1 in the intestine using colonic cell line (Caco-2).…”

Effect of High Protein Diet and ProbioticLactobacillus caseiShirota Supplementation in Aflatoxin B1-Induced Rats

“…Similar to hepatocytes, intestinal epithelial cells express CYPs capable of converting AFB 1 into the reactive epoxide; therefore AFB 1 exposure might also promote weight loss through enteropathic effects. It is likely that environmental enteropathy is common in areas where dietary AFB 1 exposure is endemic [ 58 ]. Such enteropathy is associated with histological changes in the small intestine, particularly inflammation and abnormal growth of intestinal cells.…”

Elucidating Adverse Nutritional Implications of Exposure to Endocrine-Disrupting Chemicals and Mycotoxins through Stable Isotope Techniques

“…Commonly used biomarkers for aflatoxin exposure are aflatoxin albumin adduct in serum and aflatoxin M1, a less toxic metabolite of AFB1, in body fluids such as urine and breast milk [ 44 , 51 ]. Aflatoxin exposure has been linked to impaired growth [ 14 , 22 ] and kwashiorkor [ 50 ], and may also have a role in the modification of the aetiology of hepatitis B [ 52 , 53 ] in African children. A longitudinal study from Benin assessed the association between aflatoxin exposure and growth, vitamin A and zinc plasma levels in 200 children 16–37 months of age [ 14 ].…”