Fumonisin B1 induces endoplasmic reticulum damage and inflammation by activating the NXR response and disrupting the normal CYP450 system, leading to liver damage in juvenile quail

Abstract

Fumonisin B₁ (FB₁) is a mycotoxin affecting animal health through the food chain and has been closely associated with several diseases such as pulmonary edema in pigs and diarrhea in poultry. FB₁ is mainly metabolized in the liver. Although a few studies have shown that FB₁ causes liver damage, the molecular mechanism of liver damage is unclear. This study aimed to evaluate the role of liver damage, nuclear xenobiotic receptor (NXR) response and cytochrome P450 (CYP450)-mediated defense response during FB₁ exposure. A total of 120 young quails were equally divided into two groups (control and FB₁ groups). The quails in the control group were fed on a normal diet, while those in the FB₁ group were fed on a quail diet containing 30 mg/kg for 42 days. Histopathological and ultrastructural changes in the liver, biochemical parameters, inflammatory factors, endoplasmic reticulum (ER) factors, NXR response and CYP450 cluster system and other related genes were examined at 14 days, 28 days and 42 days. The results showed that FB₁ exposure impaired the metabolic function and caused liver injury. FB₁ caused ER stress and decreased adenosine triphosphatease activity, induced the expression of inflammation-related genes such as interleukin 6 and nuclear factor kappa-B, and promoted inflammation. In addition, FB₁ disrupted the expression of multiple CYP450 isoforms by activating nuclear xenobiotic receptors (NXRs). The present study confirms that FB₁ exposure disturbs the homeostasis of cytochrome P450 systems (CYP450s) in quail liver by activating NXR responses and thereby causing liver damage. This study's findings provide insight into the molecular mechanisms of FB₁-induced hepatotoxicity.