Carbamazepine induces hepatotoxicity in zebrafish by inhibition of the Wnt/β-catenin signaling pathway

Bai, Zhonghui; Jia, Kun; Chen, Guilan; Liao, Xinjun; Cao, Zigang; Zhao, Yangqi; Zhang, Chunping; Lu, Huiqiang

doi:10.1016/j.envpol.2021.116688

Cited by 29 publications

(10 citation statements)

References 34 publications

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“…The downregulation of cell cycle key genes ccne1, cdk2, cdk6, and the upregulation of ccnd1 suggested that cell proliferation was also seriously affected by the disordered expression of these genes. According to previous publications, excessive accumulation of ROS leads to oxidative stress, affects mitochondrial function, hinders cell proliferation, and further promotes cell apoptosis (Bai et al, 2021;Wan et al, 2021). Therefore, the apoptosis of zebrafish skeletal cells exposed to cysteamine was probably mediated by oxidative stress.…”

Section: Discussionmentioning

confidence: 91%

Cysteamine affects skeletal development and impairs motor behavior in zebrafish

Chen

Zheng²,

Li³

et al. 2022

Front. Pharmacol.

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Cysteamine is a kind of feed additive commonly used in agricultural production. It is also the only targeted agent for the treatment of cystinosis, and there are some side effects in clinical applications. However, the potential skeletal toxicity remains to be further elucidated. In this study, a zebrafish model was for the first time utilized to synthetically appraise the skeletal developmental defects induced by cysteamine. The embryos were treated with 0.35, 0.70, and 1.05 mM cysteamine from 6 h post fertilization (hpf) to 72 hpf. Substantial skeletal alterations were manifested as shortened body length, chondropenia, and abnormal somite development. The results of spontaneous tail coiling at 24 hpf and locomotion at 120 hpf revealed that cysteamine decreased behavioral abilities. Moreover, the level of oxidative stress in the skeleton ascended after cysteamine exposure. Transcriptional examination showed that cysteamine upregulated the expression of osteoclast-related genes but did not affect osteoblast-related genes expression. Additionally, cysteamine exposure caused the downregulation of the Notch signaling and activating of Notch signaling partially attenuated skeletal defects. Collectively, our study suggests that cysteamine leads to skeletal developmental defects and reduces locomotion activity. This hazard may be associated with cysteamine-mediated inhibition of the Notch signaling and disorganization of notochordal cells due to oxidative stress and apoptosis.

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Section: Discussionmentioning

confidence: 91%

Cysteamine affects skeletal development and impairs motor behavior in zebrafish

Chen

Zheng²,

Li³

et al. 2022

Front. Pharmacol.

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“…These results demonstrated that P 29 is the most active promoter in Lm at 28 °C. A suitable growth temperature for carps and zebrafish is 28 °C [ 21 , 22 ]. Therefore, it has great potential to be used in aquatic vaccines based on Lm live vector to express target antigens.…”

Section: Resultsmentioning

confidence: 99%

“…The most common growth temperature for Lm EGD-e in lab settings is 37 °C [ 14 , 18 – 20 ]. A suitable growth temperature for fish, including carps and zebrafish, is 28 °C [ 21 , 22 ]. The strong promoters selected under this temperature would have the potential to be used in the application of aquatic vaccine vectors.…”

Section: Introductionmentioning

confidence: 99%

Systematic identification of a panel of strong promoter regions from Listeria monocytogenes for fine-tuning gene expression

Wang

et al. 2021

Microb Cell Fact

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Background Attenuated Listeria monocytogenes (Lm) has been widely used as a vaccine vector in the prevention and treatment of pathogen infection and tumor diseases. In addition, previous studies have proved that the attenuated Lm can protect zebrafish from Vibrio infections, indicating that the attenuated Lm has a good application prospect in the field of aquatic vaccines. However, the limitation mainly lies in the lack of a set of well-characterized natural promoters for the expression of target antigens in attenuated Lm. Results In our study, candidate strong promoters were identified through RNA-seq analysis, and characterized in Lm through enhanced green fluorescent protein (EGFP). Nine native promoters that showed stronger activities than that of the known strong promoter P36 under two tested temperatures (28 and 37 °C) were selected from the set, and P29 with the highest activity was 24-fold greater than P36. Furthermore, we demonstrated that P29 could initiate EGFP expression in ZF4 cells and zebrafish embryos. Conclusions This well-characterized promoter library can be used to fine-tune the expression of different proteins in Lm. The availability of a well-characterized promoter toolbox of Lm is essential for the analysis of yield increase for biotechnology applications.

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“…Similarly, some studies showed that after carbamazepine treatment, the mRNA of dkk1 and dkk2 was significantly up-regulated, which led to the inhibition of the Wnt/ßcatenin signaling pathway and finally induced zebrafish hepatotoxicity (Bai et al, 2021).…”

Section: Discussionmentioning

confidence: 97%

Transcriptome Analysis Reveals Hepatotoxicity in Zebrafish Induced by Cyhalofop-Butyl

Zhou¹,

Liu²,

Yang³

et al. 2022

Preprint

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Cyhalofop-butyl is a highly effective aryloxyphenoxypropionate herbicide and widely used for weed control in paddy fields. With the increasing residue of herbicides, it poses a threat to the survival of aquatic organisms. Here, we evaluated the effect of cyhalofop-butyl on zebrafish to explore its potential hepatotoxic mechanism. The results showed that cyhalofop-butyl (0.1, 0.2 and 0.4 mg/L) induced hepatocyte degeneration, vacuolation and necrosis of larvae after embryonic exposure for 4 days and caused liver atrophy after exposure for 5 days. Meanwhile, the activities of enzymes related to liver function named alanine transaminase (ALT), aspartate transaminase (AST) were significantly increased by 0.2 mg/L cyhalofop-butyl and higher. And the contents of triglyceride (TG) involved in lipid metabolism was significantly decreased by 0.4 mg/L cyhalofop-buty. The effects of cyhalofop-butyl on zebrafish larvae were further demonstrated by GO (Gene Ontology) and KEGG pathway analysis. Cyhalofop-butyl (0.1, 0.2, 0.4 mg/L) altered the expression of 116, 154, 397 genes in liver，these genes are mainly enriched in metabolism (such as lipid metabolism, amino acid metabolism), immune system (Toll-like receptor signaling pathway) and endocrine system (PPAR signaling pathway). Furthermore, the expression of key genes related to liver development combined with RNA-Seq results, indicated that cyhalofop-butyl might damage the liver development of zebrafish larvae and cause metabolic disorders. To sum up, our research results reveal the physiological and molecular responses of zebrafish liver to cyhalofop-butyl and provide new insights for further studying the mechanism of cyhalofop-butyl toxicity to aquatic organisms.

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Carbamazepine induces hepatotoxicity in zebrafish by inhibition of the Wnt/β-catenin signaling pathway

Cited by 29 publications

References 34 publications

Cysteamine affects skeletal development and impairs motor behavior in zebrafish

Cysteamine affects skeletal development and impairs motor behavior in zebrafish

Systematic identification of a panel of strong promoter regions from Listeria monocytogenes for fine-tuning gene expression

Transcriptome Analysis Reveals Hepatotoxicity in Zebrafish Induced by Cyhalofop-Butyl

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