Effects of di-(2-ethylhexyl) phthalate (DEHP) on behavior and dopamine signaling in zebrafish (Danio rerio). 2022

Wenlong Huang, and Jiefeng Xiao, and Xiaoling Shi, and Shukai Zheng, and Haiyi Li, and Caixia Liu, and Kusheng Wu
Department of Preventive Medicine, Shantou University Medical College, Shantou 515041, Guangdong, PR China.

Di (2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer, also known as a developmental toxicant, but its neurobehavioral toxicity remains elusive. This study evaluated the neurobehavioral toxicity and its possible mechanism in larval zebrafish. Embryos at gastrula period (~6 h post fertilization, hpf) were exposure to DEHP (0, 1, 2.5, 5 and 10 mg/L) for 7 days. Spontaneous tail movement in embryos and swimming activity in larvae were monitored. Alterations in the mRNA expression of genes involved in dopamine signaling and apoptosis pathway were assessed. In situ apoptotic cells were assessed by Acridine orange staining, and oxidative damage were measured using enzymatic assay. The behavior results showed that DEHP inhibited spontaneous tail movement and decreased locomotor activities in the light/dark behavioral test. Meanwhile, behavioral changes were accompanied by increased apoptosis and malondialdehyde (MDA) content, decreased superoxide dismutase (SOD) activity and dopamine (DA) content, and perturbed the expression of genes associated with the synthesis (th), reuptake (dat) and metabolism (mao) of DA, with dopamine receptors (DRs), and with the apoptosis pathway (p53, bax, bcl2, caspase-3, caspase-8, caspase-9). The findings will help to illuminate the possible neurobehavioral toxicity mechanisms of organism exposure to DEHP.

UI MeSH Term Description Entries
D007814 Larva Wormlike or grublike stage, following the egg in the life cycle of insects, worms, and other metamorphosing animals. Maggots,Tadpoles,Larvae,Maggot,Tadpole
D010795 Phthalic Acids A group of compounds that has the general structure of a dicarboxylic acid-substituted benzene ring. The ortho-isomer is used in dye manufacture. (Dorland, 28th ed) Acids, Phthalic
D010968 Plasticizers Materials incorporated mechanically in plastics (usually PVC) to increase flexibility, workability or distensibility; due to the non-chemical inclusion, plasticizers leach out from the plastic and are found in body fluids and the general environment. Plasticizer
D004051 Diethylhexyl Phthalate An ester of phthalic acid. It appears as a light-colored, odorless liquid and is used as a plasticizer for many resins and elastomers. Dioctyl Phthalate,Bis(2-ethylhexyl)phthalate,DEHP,Di(2-ethylhexyl)phthalate,Di-2-Ethylhexylphthalate,Di 2 Ethylhexylphthalate,Phthalate, Diethylhexyl,Phthalate, Dioctyl
D004298 Dopamine One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action. Hydroxytyramine,3,4-Dihydroxyphenethylamine,4-(2-Aminoethyl)-1,2-benzenediol,Dopamine Hydrochloride,Intropin,3,4 Dihydroxyphenethylamine,Hydrochloride, Dopamine
D000072105 Superoxide Dismutase-1 A superoxide dismutase (SOD1) that requires copper and zinc ions for its activity to destroy SUPEROXIDE FREE RADICALS within the CYTOPLASM. Mutations in the SOD1 gene are associated with AMYOTROPHIC LATERAL SCLEROSIS-1. Cu-Zn Superoxide Dismutase,Cuprozinc Superoxide Dismutase,SOD-1 Protein,SOD1 Protein,Superoxide Dismutase 1,Cu Zn Superoxide Dismutase,SOD 1 Protein,Superoxide Dismutase, Cu-Zn,Superoxide Dismutase, Cuprozinc
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015027 Zebrafish An exotic species of the family CYPRINIDAE, originally from Asia, that has been introduced in North America. Zebrafish is a model organism for drug assay and cancer research. Brachydanio rerio,Danio rerio,B. rerio,D. rerio,Zebra Fish,Zebra Fishes,Zebra danio,Zebrafishes,D. rerios,Fishes, Zebra,Zebra danios,danio, Zebra
D018384 Oxidative Stress A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). Anti-oxidative Stress,Antioxidative Stress,DNA Oxidative Damage,Nitro-Oxidative Stress,Oxidative Cleavage,Oxidative DNA Damage,Oxidative Damage,Oxidative Injury,Oxidative Nitrative Stress,Oxidative Stress Injury,Oxidative and Nitrosative Stress,Stress, Oxidative,Anti oxidative Stress,Anti-oxidative Stresses,Antioxidative Stresses,Cleavage, Oxidative,DNA Damage, Oxidative,DNA Oxidative Damages,Damage, DNA Oxidative,Damage, Oxidative,Damage, Oxidative DNA,Injury, Oxidative,Injury, Oxidative Stress,Nitrative Stress, Oxidative,Nitro Oxidative Stress,Nitro-Oxidative Stresses,Oxidative Cleavages,Oxidative DNA Damages,Oxidative Damage, DNA,Oxidative Damages,Oxidative Injuries,Oxidative Nitrative Stresses,Oxidative Stress Injuries,Oxidative Stresses,Stress Injury, Oxidative,Stress, Anti-oxidative,Stress, Antioxidative,Stress, Nitro-Oxidative,Stress, Oxidative Nitrative,Stresses, Nitro-Oxidative

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