Assessing the mechanisms and adjunctive therapy for arsenic‐induced liver injury in rats

Environmental arsenic exposure is a significant global public health concern. Previous studies have demonstrated the association between arsenic-induced liver injury and oxidative stress as well as ferroptosis. However, the knowledge of the interactions among these mechanisms remains limited. Moreover, there is a lack of research on potential therapeutic interventions for liver injury resulting from arsenic exposure. To address these limitations, we established a rat model with liver injury caused by arsenic exposure and investigated the impact of the nuclear factor E2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPx4) signaling pathway and ferroptosis on arsenic-induced liver injury. Our findings revealed that arsenic increased Nrf2 expression and decreased GPx4 expression in the rat liver. This was accompanied by a substantial generation of reactive oxygen species and disruption of the antioxidant defense system, ultimately promoting liver injury through ferroptosis. Subsequently, we conducted intervention experiments using Rosa roxburghii Tratt (RRT) in rats exposed to arsenic. The results showed that the detrimental effects mentioned earlier were partially alleviated following RRT intervention. This study offers preliminary evidence that persistent activation of Nrf2 by arsenic triggers an adaptive antioxidant response, leading to liver injury through the promotion of ferroptosis. Additionally, we discovered that RRT inhibits Nrf2-mediated adaptive antioxidant responses by reducing hepatic ferroptosis, thereby mitigating liver injury caused by arsenic exposure in rats. Our study contributes to a deeper understanding of the molecular mechanisms underlying liver injury resulting from arsenic exposure. Furthermore, our findings may facilitate the identification of a potential edible and medicinal plant extracts that could be utilized to develop a more effective adjunctive treatment approach.