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Arsenic poisoning is a geochemical disease that seriously endangers human health. The liver is one of the important target organs for arsenic poisoning, several studies have shown that oxidative stress plays an important role in arsenic-induced liver damage. However, the specific mechanism of arsenic-induced oxidative stress has not yet been fully elucidated, and currently, there are no effective intervention measures for the prevention and treatment of arsenic-induced liver damage. In this study, the effect of the Nrf2/GPX4 signaling pathway and oxidative stress in the arsenic-induced liver damage was first evaluated. The results show that arsenic can activate the Nrf2/GPX4 signaling pathway and increase the oxidative stress, which in turn promotes arsenic-induced liver damage in MIHA cells. Moreover, when we applied the Nrf2 inhibitor, the promoting effect of arsenic on liver damage was alleviated by inhibiting the activation of the Nrf2/GPX4 signaling pathway. Subsequently, the Rosa roxburghii Tratt [Rosaceae] (RRT) intervention experiments in cells and arsenic poisoning population were designed. The results revealed that RRT can inhibit Nrf2/GPX4 signaling pathway to reduce oxidative stress, thereby alleviates arsenic-induced liver damage. This study provides some limited evidence that arsenite can activate Nrf2/GPX4 signaling pathway to induce oxidative stress, which in turn promotes arsenic-induced liver damage in MIHA cells. The second major finding was that Kaji-ichigoside F1 may be a potential bioactive compound of RRT, which can inhibit Nrf2/GPX4 signaling pathway to reduce oxidative stress, thereby alleviates arsenic-induced liver damage. Our study will contribute to a deeper understanding of the mechanisms in arsenic-induced liver damage, these findings will identify a possible natural medicinal food dual-purpose fruit, RRT, as a more effective prevention and control strategies for arsenic poisoning., Competing Interests: The authors declare they have no actual or potential competing financial interests., (Copyright © 2022 Yuyan Xu et al.)

Exposure to arsenic-contaminated air and food caused by the burning of coal in unventilated indoor stoves is a major environmental public health concern in Guizhou Province, China. The liver is one of the main target organs for coal-fired arsenic exposure; however, there is little information about the risk assessment between cumulative arsenic exposure and the prevalence of liver damage. This study first evaluated the chronic daily intake (CDI) for two exposure pathways (inhalation and ingestion) and five environmental media (i.e., indoor and outdoor air, drinking water, rice, corn, and chili peppers) in 1998, 2006, 2014, and 2017. Then, the dose-effect and dose-response relationship between hair arsenic (HA) and cumulative arsenic (CA) levels and liver damage was analyzed. The results clearly show that the CDI in 1998 was 34.9 μg·kg -1 ·d -1 , 22.9 μg·kg -1 ·d -1 in 2006, 11.7 μg·kg -1 ·d -1 in 2014, and 6.7 μg·kg -1 ·d -1 in 2017 in the arsenic exposure area. All of these values were higher than the daily baseline level of 3.0 μg·kg -1 ·d -1 as recommended by the Joint FAO/WHO Expert Committee on Food Additives (JECFA), and the increased HA and CA can increase the risk of coal-fired arsenic-induced liver damage. In addition, we analyzed the possible maximum acceptable CA exposure level for coal-fired arsenic-induced liver damage using the Bayesian benchmark dose. The recommended maximum acceptable CA exposure level for liver damage caused by coal-burning arsenic is 7120 mg. This study provides scientific insight into understanding the dose-response relationship of liver damage caused by coal-burning arsenic exposure and the monitoring and prevention of arsenic poisoning., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Environmental exposure to arsenic is a major public health challenge worldwide. Growing evidence indicates that coal-burning arsenic can cause hepatic oxidative damage. However, the value of Rosa roxburghii Tratt (RRT) with antioxidant properties on arsenic-caused hepatic oxidative damage has never been elucidated yet. In this study, the animals were exposed to coal-burning arsenic (10 mg/kg bw) for 90 days and the result showed a loss of body weight, impaired liver function and liver diseases, increased hepatic oxidative damage and metabolic disorder of multiple elements including selenium, copper, zinc which were related to synthesis of antioxidant enzymes. Another finding is that RRT restored the abnormal liver function and alleviated the procedures of liver diseases of arsenic poisoning rats. In addition, it could also effectively reduce the degree of oxidative damage in serum and liver, and restore the activity of some antioxidant enzymes. Importantly, RRT reversed the content of most disordered elements caused by arsenic in liver and reduced the excretion of several essential elements in urine, including selenium, copper and zinc. Our study provides some limited evidence that RRT can alleviate coal-burning arsenic-induced liver damage induced by regulating elemental metabolic disorders and liver oxidation and antioxidant balance. The study provides a scientific basis for further studies of the causes of the arsenic-induced liver damage, and effective intervention strategies.

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. [ABSTRACT FROM AUTHOR]

Chronic exposure to combined fluoride (F) and arsenic (As) continues to be a major public health problem worldwide, attracting the attention of an increasing number of researchers. While bone is the main target organ of syndrome of endemic arsenic poisoning and fluorosis (SEAF), the specific mechanism and targeted intervention remains uncertain. The first question in this study sought to determine the interaction of F and As on the Wnt signaling pathway and its role in osteogenic differentiation in the SEAF population. As can be seen from the data, with the increase in exposure to F, the content of Wnt signaling inhibitor Dickkopf-related protein 1 (DKK1) gradually decreased, but the expression of glycogen synthase kinase-3β (GSK3β), β-catenin and the osteogenic differentiation indicators pro-collagen I alpha 1 (COL1A1) and bone alkaline phosphatase (BALP) were increased. Next, we grouped the SEAF population according to urinary As and found that As can upregulate the GSK3β, β-catenin level and the bone formation bio-marker BALP in serum. But the experiments did not detect any evidence that As can change the content of DKK1 in serum. To better understand the combined effects of F and As on the Wnt signaling pathway, we performed further interaction analysis. These results suggest that the interaction of F and As can inhibit the GSK3β, β-catenin, COL1A1 and BALP. And DKK1 is mainly manifested by the independent effect of F. To further study the role of DKK1 and GSK3β in fluoride-arsenic pollution combined with osteogenic differentiation, we attempted to silence the DKK1 and GSK3β gene in hFOB 1.19 cells. The results show that F, As alone and in combination exposure can up-regulate GSK catenin transcription and protein expression levels and down-regulate DKK1, and COL1A1 and ALP are significantly increased, after silenced the DKK1. The same results did not appear after silenced the GSK3β. F and As alone and in combination exposure did not reverse the inhibition of GSK3β and β-catenin by GSK3β silencing, and COL1A1 and ALP are significantly decreased. The results indicate that silencing GSK3β instead of DKK1 can inhibit osteogenic differentiation caused by co-exposure to fluoride and arsenic. This study can provide a scientific basis for further understanding the causes of bone formation caused by F and As and the improvement of targeted intervention strategies. Unlabelled Image • Wnt signaling is involved in the osteogenic differentiation caused by co-exposure to F and As. • Silencing GSK3β can inhibit osteogenic differentiation caused by co-exposure to F and As. • Silencing DKK1 cannot inhibit osteogenic differentiation caused by co-exposure to F and As. • The interaction between F and As of the Wnt signaling occurs mainly as antagonism. [ABSTRACT FROM AUTHOR]