Oxyfluorfen induces hepatotoxicity through lipo-sugar accumulation and inflammation in zebrafish (Danio rerio)

Li, Zekun; Guo, Jianbin; Jia, Kun; Zheng, Zhong; Chen, Xiaomei; Bai, Zhonghui; Yang, Yu-Jun; Chen, Bin; Yuan, Wei; Yang, Jian

doi:10.1016/j.ecoenv.2021.113140

Cited by 16 publications

(7 citation statements)

References 39 publications

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“…In agreement, OFN, FPB, and PFE kill weeds through the overproduction of ROS which causes lipid peroxidation and damage to the cell membrane and finally cell death [20,29,30]. Similar oxidative stress dependant cytotoxic effects were also reported in fish for OFN [22][23][24][25][26][27], and in rat liver, kidney and testis for FPB [32]. However, no cytotoxic potential has been reported for PFE on animals or humans so far [29].…”

Section: Discussionmentioning

confidence: 55%

“…It also has ROS-dependent cyto-and geno-toxic effects on fish and other aquatic invertebrates [22][23][24][25][26]. In zebrafish, OFN disrupts hepatic lipid and glucose metabolism during embryonic development and causes hepatocyte mortality by increasing inflammatory factors [27]. OFN induces promotes cell cycle arrest through the regulation of MAPK, PI3K, and autophagy in bovine mammary epithelial cells [28].…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of Four Herbicides Cytotoxicity on Normal Liver THLE2 Cells

Al-Mathal,

Khaffagy,

Abu El-Magd

2024

Egyptian Journal of Veterinary Sciences

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HE widespread increase in pesticide use is a source of pollution worldwide. Although herbicides have various applications, they nonetheless represent a risk to human health due to their tendency to bioaccumulate in many different environments. The purpose of this research was to investigate the cytotoxic effects of pendimethalin (PEN), oxyfluorfen (OFN), fluazifop-p-butyl (FPB), and pyraflufen ethyl (PFE) herbicides on human normal liver (THLE2) cells through the evaluation of the cell viability (using the MTT assay), apoptosis (using qPCR), cell cycle (using flowcytometry), and oxidative stress status (using biochemical assays). The four herbicides induced cytotoxic effects on THLE2 cells as evidenced by suppressed cell viability with IC50 values as follows: PEN (60.50±3.19 μM), OFN (100.36±4.66 μM), FPB (174.90±6.54 μM) and PFE (186.72±6.82 μM). They also increased apoptosis (high Bax and caspase 3, and low Bcl2 gene expression). However, only PEN and OFN induced cell cycle arrest in G0/G1 and both S and G2/M phases, respectively, with subsequent downregulated expression of cyclin D1, cyclin A2, and cyclindependent kinase 4 (CDK4). Among the four herbicides, only OFN, PFE, and FPB induced oxidative stress damage as revealed by higher levels of intracellular reactive oxygen species (ROS) and malondialdehyde (MDA), inhibited activities of antioxidant enzymes [catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx)], and downregulated expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) genes. FPB and PFE had a greater safety margin on human normal THLE2 cells and might be used with less adverse consequences on human and animal health.

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Section: Discussionmentioning

confidence: 55%

Section: Introductionmentioning

confidence: 99%

Evaluation of Four Herbicides Cytotoxicity on Normal Liver THLE2 Cells

Al-Mathal,

Khaffagy,

Abu El-Magd

2024

Egyptian Journal of Veterinary Sciences

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“…The higher sensitivity of bivalve species to Cu than to organic pesticides, such as oxyfluorfen, can be explained by the pesticide action mode, which is designed to act essentially on vegetal cells, while Cu is non-selective, and regardless of its essential role in the biological functions of organisms at trace levels, it becomes toxic at high levels. Additionally, by comparing the oxyfluorfen lethality between C. edule and other studies with fish species, the chemical showed to be more toxic to fish species, such as Clarias gariepinus (LC 50 = 11.698 mg L −1 ), Danio rerio (LC 50 = 6.654 mg L −1 ) and Oreochromis niloticus (LC 50 = 3 mg L −1 ) [ 17 , 64 , 65 ].…”

Section: Resultsmentioning

confidence: 99%

Effects of Inorganic and Organic Pollutants on the Biomarkers’ Response of Cerastoderma edule under Temperature Scenarios

Mesquita,

Gonçalves,

Gonçalves

2023

Antioxidants

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Currently, there is increased chemical pollution, and climate change is a major concern to scientific, political and social communities globally. Marine systems are very susceptible to changes, and considering the ecological and economic roles of bivalve species, like Cerastoderma edule, studies evaluating the effects of both stressors are of great importance. This study intends to (a) determine the toxicity of copper (Cu) and oxyfluorfen at the lethal level, considering the temperature; (b) assess the changes in the antioxidant defence enzymes as a consequence of the simultaneous exposure to chemical and warming pressures; and (c) determine if lipid peroxidation (LPO) and neurotoxic effects occur after the exposure to chemical and temperature stressors. C. edule was exposed to Cu and oxyfluorfen at different temperatures (15 °C, 20 °C and 25 °C) for 96 h. The ecotoxicological results reveal a higher tolerance of C. edule to oxyfluorfen than to Cu, regardless of the temperature. The antioxidant defence system revealed efficiency in fighting the chemicals’ action, with no significant changes in the thiobarbituric reactive species (TBARS) levels to 15 °C and 20 °C. However, a significant inhibition of acetylcholinesterase (AChE) was observed on the organisms exposed to oxyfluorfen at 20 °C, as well as a decreasing trend on the ones exposed to Cu at this temperature. Moreover, the catalase (CAT) showed a significant increase in the organisms exposed to the two highest concentrations of Cu at 15 °C and in the ones exposed to the highest concentration of oxyfluorfen at 20 °C. Looking at the temperature as a single stressor, the organisms exposed to 25 °C revealed a significant increase in the TBARS level, suggesting potential LPO and explaining the great mortality at this condition.

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“…For example, thiophanate-methyl induces hepatotoxicity through zebrafish apoptosis and oxidative stress, and then leads to a metabolic imbalance of zebrafish liver (Jia et al, 2020). Oxyfluorfen damaged the lipid and sugar metabolism in the liver of zebrafish larvae, and the liver injury caused by metabolic dysfunction eventually affected the early development of zebrafish (Li et al, 2021). The combined hepatotoxicity in imidacloprid and microplastics caused the changes of glucose and lipid metabolism and the expression of inflammation-related genes in zebrafish (Luo et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Transcriptome analysis reveals hepatotoxicity in zebrafish induced by cyhalofop-butyl

Zhou

Yang

Liu

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.Graphical AbstractHighlightsCyhalofop-butyl induced liver damage of zebrafish larvae and caused liver atrophyCyhalofop-butyl affected liver function by increasing the activities of ALT and AST.Cyhalofop-butyl disturbed the lipid metabolism of liver in zebrafish via inhibition TG levels.Cyhalofop-butyl exposure induced metabolism and immune system disturbance at transcriptional levels.

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Oxyfluorfen induces hepatotoxicity through lipo-sugar accumulation and inflammation in zebrafish (Danio rerio)

Cited by 16 publications

References 39 publications

Evaluation of Four Herbicides Cytotoxicity on Normal Liver THLE2 Cells

Evaluation of Four Herbicides Cytotoxicity on Normal Liver THLE2 Cells

Effects of Inorganic and Organic Pollutants on the Biomarkers’ Response of Cerastoderma edule under Temperature Scenarios

Transcriptome analysis reveals hepatotoxicity in zebrafish induced by cyhalofop-butyl

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