Environmentally relevant concentrations of di(2-ethylhexyl)phthalate exposure alter larval growth and locomotion in medaka fish via multiple pathways

Yang, Wenkai; Chiang, Li-Fen; Tan, Shih-Wei; Chen, Pei‐Jen

doi:10.1016/j.scitotenv.2018.05.312

Cited by 60 publications

(9 citation statements)

References 86 publications

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“…We observed downregulation of sod1 , sod2 and sod3 by all the doses of DINCH. It has previously been indicated that these genes were affected by several plasticizers such as DEHP, dimethyl phthalate (DMP), and butyl benzyl phthalate (BBP) in zebrafish and medaka fish ( Cong et al., 2020 ; Yang et al., 2018 ; Zhang et al., 2014 ). It has also been shown that SOD1 enzyme activity was overexpressed in response to subacute exposure to DINCH at post-natal day 21 of dams, while it was repressed upon in utero exposure to DINCH at post-natal day 60 in a dose-dependent manner ( Campioli et al., 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH) alters transcriptional profiles, lipid metabolism and behavior in zebrafish larvae

Saad

Bereketoğlu

Pradhan

2021

Heliyon

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Plasticizers are commonly used in different consumer goods and personal care products to provide flexibility, durability and elasticity to polymers. Due to their reported toxicity, the use of several plasticizers, including phthalates has been regulated and/or banned from the market. Di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH) is an alternative plasticizer that was introduced to replace toxic plasticizers. Increasing global demand and lack of toxicity data and safety assessment of DINCH have raised the concern to human and animal health. Hence, in the present study, we investigated the adverse effects of DINCH (at concentrations ranging from 0.01 to 10 μM) in early developmental stages of zebrafish using different endpoints such as hatching rate, developmental abnormalities, lipid content, behavior analysis and gene expression. We found that DINCH caused hatching delay in a dose-dependent manner and altered the expression of genes involved in stress response. Lipid staining using Oil Red O stain showed a slight lipid accumulation around the yolk, brain, eye and neck with increasing concentration. Genes associated with lipid transport such as fatty acid synthesis, β-oxidation, elongation, lipid transport were significantly altered by DINCH. Genes involved in cholesterol biosynthesis and homeostasis were also affected by DINCH indicating possible developmental neurotoxicity. Behavioral analysis of larvae demonstrated a distinct locomotor activity upon exposure to DINCH. The present data shows that DINCH could induce physiological and metabolic toxicity to aquatic organisms. Hence, further analyses and environmental monitoring of DINCH should be conducted to determine its safety and toxicity levels.

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Section: Discussionmentioning

confidence: 99%

Di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH) alters transcriptional profiles, lipid metabolism and behavior in zebrafish larvae

Saad

Bereketoğlu

Pradhan

2021

Heliyon

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“…Each concentration in the DMP groups had 4 replicates with 80 fish each, and the control groups had the same replicates. For each time endpoint (24,48, and 96 h), liver samples were dissected from 20 living fish (2.5 ± 0.3 cm and weight 0.22 ± 0.05 g) in each group via a stereomicroscope washing twice with phosphate buffer saline (PBS) on an ice-cold plate and divided into 2 samples: 15 individuals were used to assay MDA and antioxidant enzyme activity, and 5 individuals were used for real-time polymerase chain reaction (RT-PCR).…”

Section: Exposure Experiments and Sample Collectionmentioning

confidence: 99%

“…Zhang et al (2014) discovered that low concentrations of benzyl butyl phthalate (BBP) could stimulate superoxide dismutase (SOD) activity, while high concentrations inhibited this activity and the mRNA levels of SOD inhibition decreased and then increased in the muscles of zebrafish after 7 days of exposure [23]. Yang et al (2018) demonstrated that di (2-ethylhexyl) phthalate (DEHP) exposure at 20, 100 and 200 µg/L over 21 days suppressed the activity and transcriptional expression of the antioxidant enzymes SOD, catalase (CAT) and glutathione s-transferase (GST) in the fry of medaka fish [24]. More recently, Qu et al (2015) and Zheng et al (2013) reported that in Carassius auratus, when the fish were injected with 17 different PAEs at a concentration of 10 mg/kg for several days, respectively, the activities of antioxidant enzymes (SOD and CAT) were inhibited by DMP with an increasing treatment time [19,25].…”

mentioning

confidence: 99%

The Impact on Antioxidant Enzyme Activity and Related Gene Expression Following Adult Zebrafish (Danio rerio) Exposure to Dimethyl Phthalate

Cong

Liu

Wang

et al. 2020

Animals

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Dimethyl phthalate (DMP) is a widespread environmental contaminant that poses potential toxicity risks for animals and humans. However, the toxicological effects of DMP on fish have not been adequately examined. In this study, the acute toxicity, oxidative damage, antioxidant enzyme activities, and relative gene expression patterns were investigated in the liver of adult zebrafish (Danio rerio) exposed to DMP. We found that the lethal concentration (LC50) of DMP for zebrafish after 96 h of exposure was 45.8 mg/L. The zebrafish that were exposed to low, medium and high concentrations of DMP (0.5, 4.6, and 22.9 mg/L, respectively) for 96 h had an increased malondialdehyde (MDA) content and a lower antioxidant capacity compared with the control solvent group. The total superoxide dismutase (SOD) activity was significantly higher than 0 h after initial exposure for 24 h at low concentrations, and then decreased at high concentrations after exposure for 96 h. The catalase (CAT) and glutathione S-transferase (GST) activities were significantly reduced after 96 h of exposure to high concentrations of DMP, with the up- or down-regulation of the related transcriptional expression. These findings indicated that DMP could cause physiological effects in zebrafish by disturbing the expression levels of antioxidant enzymes. These results might contribute to the identification of biomarkers to monitor phthalate pollution.

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“…We observed downregulation of sod1, sod2 and sod3 by all the doses of DINCH. It has previously been indicated that these genes were affected by several plasticizers such as DEHP, dimethyl phthalate (DMP), and butyl benzyl phthalate (BBP) (Cong et al, 2020;Yang et al, 2018;Zhang et al, 2014). It has also been shown that SOD1 enzyme activity was overexpressed in response to subacute exposure to DINCH at post-natal day 21 of dams, while it was repressed upon in utero exposure to DINCH at post-natal day 60 in a dose-dependent manner (Campioli et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH) Alters Transcriptional Profiles, Lipid Metabolism and Behavior in Zebrafish Larvae

Saad

Bereketoğlu

Pradhan

2021

Preprint

View full text Add to dashboard Cite

Plasticizers are commonly used in different consumer goods and personal care products to provide flexibility, durability and elasticity to polymers. Due to their reported toxicity, the use of several plasticizers including phthalates has been regulated and/or banned from the market. Di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH) is an alternative plasticizer that was introduced to replace toxic plasticizers. Increasing global demand and lack of information regarding toxicity and safety assessment of DINCH have raised the concern to human and animal health. Hence, in the present study, we investigated the adverse effects of DINCH (at concentrations ranging from 0.01 to 10 μM) in early developmental stages of zebrafish using different endpoints such as hatching rate, developmental abnormalities, lipid metabolism, behavior analysis and gene expression. We found that DINCH caused hatching delay in a dose-dependent manner and altered the expression of genes involved in stress response. Lipid staining using Oil Red O stain showed a slight lipid accumulation around the yolk, brain, eye and neck with increasing concentration. Genes associated with lipid metabolism such as fatty acid synthesis, β-oxidation, elongation, lipid transport were significantly altered by DINCH. Behavioral analysis of larvae demonstrated a distinct locomotor activity including distance and acceleration upon exposure to DINCH both in light and dark. Genes involved in cholesterol biosynthesis and homeostasis were also affected by DINCH indicating possible developmental neurotoxicity. The present data shows that DINCH could induce physiological and metabolic toxicity to aquatic organisms. Hence, further analyses and environmental monitoring on DINCH should be conducted to determine its safety and toxicity levels.

show abstract

Environmentally relevant concentrations of di(2-ethylhexyl)phthalate exposure alter larval growth and locomotion in medaka fish via multiple pathways

Cited by 60 publications

References 86 publications

Di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH) alters transcriptional profiles, lipid metabolism and behavior in zebrafish larvae

Di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH) alters transcriptional profiles, lipid metabolism and behavior in zebrafish larvae

The Impact on Antioxidant Enzyme Activity and Related Gene Expression Following Adult Zebrafish (Danio rerio) Exposure to Dimethyl Phthalate

Di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH) Alters Transcriptional Profiles, Lipid Metabolism and Behavior in Zebrafish Larvae

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