Alginate Oligosaccharides Attenuate Ochratoxin A‐Induced Liver Injury through Regulating the Interaction of Nrf2 and NF‐κB Signaling Pathways

ABSTRACT Ochratoxin A (OTA) is one of the common contaminants in food and livestock feed. Chronic intake of OTA induces the oxidative stress and inflammation in liver, thus endangering the hepatic metabolic function and causing liver injury. Alginate oligosaccharides (AOS) are extracted from seaweeds with antioxidant and anti‐inflammatory capacities, whether AOS can alleviate OTA‐induced liver injury still needs to be further investigated. The aim of this study was to explore the effects of AOS on OTA‐induced hepatic oxidative damage and inflammation and the underlying mechanisms. The in vivo results showed that AOS alleviates OTA‐induced histological damage and inflammatory cell infiltration in the liver. Moreover, AOS mitigates OTA‐induced hepatic oxidative and inflammatory damage and improves liver metabolic function. The in vitro validation study suggested that AOS activates Nrf2 signaling through phosphorylation modification, thereby up‐regulating the expression of downstream antioxidant‐related genes and enhancing the antioxidant enzyme activities, subsequently reducing the hepatic oxidative damage by scavenging of reactive oxygen species (ROS) and inhibiting the activation of NF‐κB signaling by ROS and the production of inflammatory cytokines, ultimately alleviating the inflammatory injury in OTA‐exposed mice. Taken together, the findings demonstrate that AOS can inhibit ROS accumulation by activating the Nrf2 signaling pathway, thus suppressing the inflammatory damage mediated by the NF‐κB signaling pathway, playing a hepatoprotective role in OTA‐induced liver damage.