INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2023
·Vol. 24
·期 13
·10898
·
IF 5.6
Zhiying Liang,Yafen Guo,Duan Pi,Xiang Li,Bingying Li,Yongsi Huang,Xiaohong Song,Ramji Kumar Bhandari,Xuegeng Wang
Bisphenol F (BPF) has been used in the syntheses of polymers, which are widely used in coatings, varnishes, adhesives, and other plastics. During the past decades, BPF contamination in the aquatic environment has dramatically increased due to its release from manmade products. Concerns have driven much attention to whether it may adversely impact aquatic lives or human beings. The present study performed an acute toxic exposure experiment and a 15 d developmental exposure of BPF at environmental concentrations (20, 200, and 2000 ng/L) using Chinese medaka (Oryzias sinensis). In the acute toxic exposure, the LC50of BPF to Chinese medaka is 87.90 mg/L at 96 h. Developmental exposure induced a significant increase in the frequency of larvae with abnormalities in the 2000 ng/L BPF group compared to the control group. Transcriptomic analysis of the whole larvae revealed 565 up-regulated and 493 down-regulated genes in the 2000 ng/L BPF exposure group. Analysis of gene ontology and KEGG pathways enrichments indicated endocrine disorders to be associated with BPF-induced developmental toxicity. The present results suggest that BPF is developmentally toxic at 2000 ng/L concentration in Chinese medaka and causes endocrine-related aberrations in the transcriptional network of genes.Keywords:Bisphenol F;Chinese medaka;toxicity;developmental defects;endocrine disruptor
研究领域:
环境科学
·
毒理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2023
·
IF 6.8
Xiaorong Wu,Shiqi Li,Yangyue Ni,Caoyan Qi,Shengjun Bai,Qiaoqiao Xu,Yun Fan,Xuan Ma,Chuncheng Lu,Guizhen Du,Zhipeng Xu,Yufeng Qin
Bisphenol A (BPA) has been widely restricted, leading to a significant increase in the production of bisphenol AF (BPAF), one of the most common bisphenol analogs use as a substitute for BPA. However, there is limit evidence on the neurotoxicity of BPAF, especially the potential effects of maternal exposed to BPAF on offspring. A maternal BPAF exposure model was used to evaluate its effects on long-term neurobehaviors in offspring. We found that maternal BPAF exposure resulted in immune disorders, characterized by abnormal CD4 + T cell subsets, and their offspring exhibited anxiety- and depression-like behaviors, as well as impairments in learning-memory, sociability and social novelty. Further, brain bulk RNA-sequencing (RNA-seq) and hippocampus single-nucleus RNA-sequencing (snRNA-seq) of offspring showed that differentially expressed genes (DEGs) were enriched in pathways related to synaptic and neurodevelopment. Synaptic ultra-structure of offspring was damaged after maternal BPAF exposure. In conclusion, maternal BPAF exposure induced behavior abnormality in adult offspring, together with synaptic and neurodevelopment defects, which might be related to maternal immune dysfunction. Our results provide a comprehensive insight into the neurotoxicity mechanism of maternal BPAF exposure during gestation. Given the increasing and ubiquitous exposure to BPAF, especially during sensitive periods of growth and development, the safety of BPAF requires urgent attention.
研究领域:
毒理学
·
神经科学
·
发育生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
·
2025
·
IF 4.3
Fang Chen,Haiyan Wei,Dalong Liao,Yong Huang,Yijian Chen,Huiqiang Lu,Rong Xu
Colchicine is a type of alkaloid commonly used clinically for treating diseases such as gouty arthritis. Studies suggest that colchicine is toxic to the kidneys. However, the specific mechanisms are unclear. Herein, we used zebrafish to validate the renal toxicity of colchicine and investigate the underlying mechanisms. Zebrafish larvae at 3 days post-fertilization were exposed to various concentrations (15, 20, and 25 mg/L) of colchicine solution for 72 h. Results showed that colchicine caused death, slowed heart rate, slowed growth, increased interpupillary distance, caused periorbital and renal capsule edema, caused swelling of glomerular podocytes, and disrupted the development of distal convoluted tubules of renal tubules. ROS staining revealed that colchicine increased oxidative in the glomerular. Mature zebrafish adults were exposed to colchicine solution concentrations of 0.15 and 1.5 mg/L for 4 weeks. Hematoxylin eosin staining of the kidney showed that the glomerular podocyte structure was disordered, renal tubular nuclei were irregularly arranged, and cell density was reduced. A significant increase in oxidative stress kinase activity was observed. Additionally, there was abnormal expression of genes related to kidney development and function. Abnormalities in kidney injury biomarkers were also observed in zebrafish, including urea nitrogen (BUN), creatinine (CR), and β- N -acetylglucosaminidase (NAG). These findings suggest that colchicine induced developmental defects and caused renal toxicity in zebrafish. Interestingly, treatment with astaxanthin (ASTA) partially reversed the structural and physiological damage in the kidney. Conclusively, colchicine induces developmental and renal toxicity in zebrafish by upregulating oxidative stress.
研究领域:
毒理学
·
发育生物学
·
肾脏病学
·
药理学
·
氧化应激研究
·
分子生物学
·
斑马鱼模型
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cell Death Discovery
·
2021
·Vol. 7
·期 1
·1-10
·
IF 5.241
Bian Wan-Ping,Pu Shi-Ya,Xie Shao-Lin,Wang Chao,Deng Shun,Strauss Phyllis R.,Pei De-Sheng
MVP17 encodes a mitochondrial inner-membrane protein, and mutation of human MVP17 can cause mitochondria DNA depletion syndrome (MDDS). However, the underlying function of mpv17 is still elusive. Here, we developed a new mutant with mpv17 knockout by using the CRISPR/Cas9 system. The mpv17 −/− zebrafish showed developmental defects in muscles, liver, and energy supply. The mpv17 −/− larvae hardly survived beyond a month, and they showed abnormal growth during the development stage. Abnormal swimming ability was also found in the mpv17 −/− zebrafish. The transmission electron microscope (TEM) observation indicated that the mpv17 −/− zebrafish underwent severe mitochondria dysfunction and the disorder of mitochondrial cristae. As an energy producer, the defects of mitochondria significantly reduced ATP content in mpv17 −/− zebrafish, compared to wild-type zebrafish. We hypothesized that the disorder of mitochondria cristae was contributed to the dysfunction of muscle and liver in the mpv17 −/− zebrafish. Moreover, the content of major energy depot triglycerides (TAG) was decreased dramatically. Interestingly, after rescued with normal exogenous mitochondria by microinjection, the genes involved in the TAG metabolism pathway were recovered to a normal level. Taken together, this is the first report of developmental defects in muscles, liver, and energy supply via mitochondria dysfunction, and reveals the functional mechanism of mpv17 in zebrafish.
研究领域:
发育生物学
·
分子遗传学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2025
·
IF 8
Chuan Liang,Yang Chen,Yunzhe Ling,Peirun Li,Jiahao Liu,Xuantian Li,Yanhua Xu,Zhiying Liu
Non-steroidal anti-inflammatory drugs (NSAIDs), though designed to target specific molecular pathways, pose significant environmental risks to non-target organisms, particularly marine fish. This study investigated the toxicity mechanisms and adaptive responses to diclofenac (DCF) and meloxicam (MEX) during the early life stages (ELS) of Oryzias melastigma at environmentally relevant concentrations over a 31-day period. Mechanistic investigations of sub-lethal effects were conducted using Enzyme-Linked Immunosorbent Assay (ELISA), RNA sequencing (RNA-Seq) and quantitative PCR (qPCR). The results revealed that cyclooxygenase (COX) inhibition disrupted the renin-angiotensin system, leading to an accumulation of angiotensin II and cardiovascular developmental defects. Additionally, downregulation of the pla2 gene reduced substrates essential for COX enzyme activity, exacerbating the effects. Although NSAIDs are known to affect the digestive system, no significant effects on developmental factors were observed. RNA-Seq and qPCR analyses revealed an adaptive upregulation of key genes, including ace2 and cyp7a1 , involved in cardiovascular and metabolic regulation. Furthermore, 16S rRNA sequencing identified shifts in the microbial community, particularly in g_Rubritalea and g_Sphingomonas genera. Both the upregulated genes and the altered microbial taxa likely played a role in mitigating toxic effects and promoting homeostasis. Moreover, molecular docking suggested that MEX exhibited stronger sub-lethal effects than DCF, likely due to its higher binding affinity to COX. These findings provide valuable insights into NSAID toxicity mechanisms in marine fish, highlighting the importance of adaptive responses in countering environmental stress and underscoring the long-term ecological risks of chronic NSAID exposure.
研究领域:
海洋毒理学
·
环境科学
·
药理学
·
分子生物学
·
发育生物学
·
生态毒理学
·
微生物学
·
生物信息学
·
药物发现
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）