Impact of chronic oral aflatoxin B1 (AFB1) exposure on iron metabolism in pig model.

Aflatoxin B1 (AFB1) is a widespread food and feed contaminant with well-established hepatotoxic effects, yet its influence on iron metabolism remains poorly understood. Chronic aflatoxin exposure often coexists with anemia and disturbed micronutrient status. The present study investigated the impact of chronic oral low-dose AFB1 exposure on systemic and tissue iron homeostasis in pigs, with particular emphasis on the hepcidin–ferroportin regulatory axis and IRP/IRE-mediated mechanisms. Twenty 6-week-old commercial crossbred TN70 pigs (Norsvin Landrace x Large White) pigs were assigned to control and AFB1-treated groups; AFB1 was administered orally at 120 µg/kg body weight for the 14 consecutive days.Hematological, biochemical, molecular, and protein analyses were performed in plasma, liver, and duodenum. AFB1 exposure did not impair growth performance nor induce overt systemic iron deficiency. However, significant alterations in iron-regulatory pathways were observed. Paradoxically, increased plasma and hepatic hepcidin levels were accompanied by elevated ferroportin protein abundance in both liver and duodenum despite unchanged Fpn mRNA expression, indicating disruption of canonical hepcidin–ferroportin signaling. Hepatic DMT1 protein expression was markedly reduced, whereas TfR1 remained largely unchanged. AFB1 also increased IRP1-IRE binding activity and altered ferritin subunit expression in a tissue-specific manner: hepatic H-ferritin decreased, whereas duodenal H-ferritin increased, while L-ferritin showed only modest, non-significant changes. Collectively, these findings demonstrate that chronic low-dose AFB1 exposure selectively modifies iron transport, storage, and post-transcriptional iron-sensing pathways without overt disruption of systemic iron balance. The increase in ferroportin together with reduced hepatic DMT1 protein may represent a protective shift toward limiting intracellular iron retention during aflatoxin-induced hepatic stress, although the precise mechanisms require further investigation.