Toxicological Assessment of Trace β-Diketone Antibiotic Mixtures on Zebrafish (Danio rerio) by Proteomic Analysis

Yin, Xiaohan; Wang, Huili; Zhang, Yuna; Dahlgren, Randy A.; Zhang, Hongqin; Gao, Ming; Wang, Xuedong

doi:10.1371/journal.pone.0102731

Cited by 23 publications

(23 citation statements)

References 35 publications

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“…Each sample in each group was measured in triplicate, and each experiment was repeated at least three times. Because the expression of β‐actin does not vary with the change of environmental conditions, it is often used as a stable reference gene (Piorkowski et al, ; Yin et al, ). The quantification was normalized to endogenous control β‐actin (levels of this transcript were consistent across all samples).…”

Section: Methodsmentioning

confidence: 99%

“…The primer pairs were designed to span introns to prevent amplification of any contaminating genomic DNA. The details of these fragments are summarized in (Piorkowski et al, 2014;Yin et al, 2014). The quantification was normalized to endogenous control b-actin (levels of this transcript were consistent across all samples).…”

Section: Qrt-pcr Analysis Of Candidate Genesmentioning

confidence: 99%

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Toxicity assessment of combined fluoroquinolone and tetracycline exposure in zebrafish (Danio rerio)

et al. 2014

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Fluoroquinolones (FQs) and tetracyclines (TCs), the two b-diketone antibiotics (DKAs), are two frequently detected pollutants in the environment; however, little data are available on their combined toxicity to zebrafish (Danio rerio). This study reports that toxicologic effects of combined DKA (FQs-TCs) exposure on zebrafish were comparable with or slightly less than those of TCs alone, showing that TCs played a major toxicologic role in the mixtures. The effects of FQs, TCs, and DKAs on malformation rates of zebrafish were dose dependent, with EC 50 values of 481.3, 16.4, and 135.1 mg/L, respectively. According to the combined effects of DKAs on zebrafish hatching, mortality, and malformation rates, the interaction between FQs and TCs was shown to be antagonistic based on three assessment methods: Toxic Unit, Additional Index, and Mixture Toxic Index. The 1.56 mg/L TC and 9.38 mg/L DKA treatments resulted in higher zebrafish basal swimming rate compared with the control group at 120 hours postfertilization (hpf). in both light and light-to-dark photoperiod experiments. Under conditions of no obvious abnormality in cardiac development, the heart beats were decreased significantly because of DKA exposure, such as decreasing by 20% at 150 mg/L DKAs. Transmission electron microscopy observation of myocytes from DKA-exposed hearts displayed prominent interruptions and myofibrillar disorganization of the normal parallel alignment of thick and thin filaments, and partial edematous and dissolved membranes of cell nuclear tissues. At 90 mg/L DKAs, the transcriptional levels of the acta1a, myl7, and gle1b genes, related to heart development and skeletal muscle formation, were significantly changed. This is consistent with the swimming behavior and histopathologic results obtained by transmission electron microscopy. In summary, the toxicity of the combined DKAs to zebrafish was comparable with or less than that of TCs

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Section: Methodsmentioning

confidence: 99%

Section: Qrt-pcr Analysis Of Candidate Genesmentioning

confidence: 99%

Toxicity assessment of combined fluoroquinolone and tetracycline exposure in zebrafish (Danio rerio)

et al. 2014

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“…Previous studies have primarily focused on the toxicity of single DKA species to explore the relevant toxicological mechanisms. However, in real-world aquatic environments, mixtures of several different DKA species may have entirely different toxicological mechanisms, which can lead to complex, combined toxicity actions by DKAs mixtures [ 9 – 10 ]. For in vivo experiments, changes in metabolic transformation and distribution of DKAs make the toxicological research more complicated [ 11 – 12 ].…”

Section: Introductionmentioning

confidence: 99%

“…Zhang and coworkers [ 14 ] found that tetracycline produced oxidative stress and induced apoptosis, which brought about significant developmental delay in zebrafish embryos. Yin and coworkers [ 9 ] used proteomic analysis of zebrafish to evaluate long-term trace exposure to DKAs, and found that 47 differential expression proteins compared to the control, and the number of positive proteins was 26 with up-regulation of 14 and down-regulation of 12. Our group previously demonstrated that DKAs were developmentally toxic in the early life stages of zebrafish and impaired individual behaviors [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Immunotoxicity of β-Diketone Antibiotic Mixtures to Zebrafish (Danio rerio) by Transcriptome Analysis

Wang

Liu

et al. 2016

PLoS ONE

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Fluoroquinolones and tetracyclines are known as β-diketone antibiotics (DKAs) because of bearing a diketone group in their molecular structure. DKAs are the most widely used antibiotics to prevent generation of disease in humans and animals and to suppress bacterial growth in aquaculture. In recent years, overuse of DKAs has caused serious environmental risk due to their pseudo-persistence in the environment, even though their half-lives are not long. So far, no reports were concerned with the joint immunotoxicity of DKAs. Herein, we reported on the immunotoxicity of DKAs on zebrafish after a 3-month DKAs exposure using transcriptomic techniques. According to transcriptome sequencing, 10 differentially expressed genes were screened out among the genes related to KEGG pathways with high enrichment. The identified 7 genes showed to be consistent between RNA-seq and qRT-PCR. Due to DKAs exposure, the content or activity for a series of immune-related biomarkers (Complement 3, lysozyme, IgM and AKP) showed the inconsistent changing trends as compared with the control group. Histopathological observations showed that the number of goblet cells increased sharply, the columnar epithelial cells swelled, the nucleus became slender in intestinal villi, and numerous brown metachromatic granules occurred in spleens of DKAs-exposed groups. Overall, both detection of biomarkers and histopathological observation corroborated that chronic DKAs exposure could result in abnormal expression of immune genes and enzymes, and variable levels of damage to immune-related organs. These complex effects of DKAs may lead to zebrafish dysfunction and occurrence of diseases related to the immune system.

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“…Zebrafish and mammals have high similarity in energy metabolism, and their locomotor behavior is a direct result of nerve conduction, muscle contraction, and energy transfer (Yin et al, 2014). Creatine kinase (CK) catalyzes the reversible transfer of phosphorylases between adenosine diphosphate (ADP) and creatine phosphate, which plays an important role in cell energy metabolism.…”

Section: Detection Of Biomarkers Era and Erbmentioning

confidence: 99%

Response mechanisms to joint exposure of triclosan and its chlorinated derivatives on zebrafish (Danio rerio) behavior

et al. 2018

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h i g h l i g h t sJoint toxicity of triclosan and its main products (TDTs) to zebrafish behavior. TDTs-stress produced larval abnormality and adult anxiety-or autism-like behavior. Behavioral effects focus on social interaction, preference, T-maze tests and so on. Abnormal behavior from changes in the related gene, biomarker and pathological tissue. TDTs produced vascular ablation in head and occurrence of massive apoptosis in brain. a r t i c l e i n f o b s t r a c tTriclosan (TCS), 2,4,6-trichlorophenol (2,4,6-TCP) and 2,4-dichlorophenol (2,4-DCP) frequently co-exist in real-world aquatic environments; the latter two contaminants contributing to TCS photolytic products or chlorinated derivatives. There is a paucity of information regarding their joint toxicity to aquatic organisms leading us to study their effects on the swimming behavior of zebrafish (Danio rerio). Herein, we reported that 0.28 mg/L TDT exposure (mixtures of TCS, 2,4,6-TCP and 2,4-DCP) enhanced 24-hpf embryonic spontaneous movement frequency, 96-hpf larval activity; however, the 0.56 and 1.12 mg/L TDT treatments decreased all of these behavioral endpoints. All adult behavioral tests demonstrated that chronic TDT exposure (0.14 mg/L) led to hyperactivity and restlessness in adult zebrafish. A 0.14 mg/L TD DATE /@ "M/d/yyyy" 11/21/2017T treatment led to anxiety-like behavior in a bottom dwelling test and excessive panic and low hedging capacity in a conditioned place preference test. Social interaction test demonstrated that zebrafish preferred quiet and isolated space in response to TDT stress. Zebrafish memory was significantly decreased in a T-maze experiment. Whole mount in situ hybridization of pax2a and bcl2l11 genes revealed that their differential expression in the brain and skeleton were related to the corresponding phenotypic behavioral abnormality. A series of biomarker and estrogen receptor assays demonstrated that TDT acute exposure caused abnormal energy metabolism and neurological diseases. AO staining revealed that TDT exposure produced vascular ablation in the head, as well as the occurrence of massive apoptosis in the brain. TEM observation showed pyknosis of nucleus following TDT exposure. These results allow assessment of mechanisms for zebrafish abnormal behavior in response to TDT exposure, and are useful for early intervention and gene therapy of contaminant-induced diseases.

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Toxicological Assessment of Trace β-Diketone Antibiotic Mixtures on Zebrafish (Danio rerio) by Proteomic Analysis

Cited by 23 publications

References 35 publications

Toxicity assessment of combined fluoroquinolone and tetracycline exposure in zebrafish (Danio rerio)

Toxicity assessment of combined fluoroquinolone and tetracycline exposure in zebrafish (Danio rerio)

Immunotoxicity of β-Diketone Antibiotic Mixtures to Zebrafish (Danio rerio) by Transcriptome Analysis

Response mechanisms to joint exposure of triclosan and its chlorinated derivatives on zebrafish (Danio rerio) behavior

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