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Naringenin (NGN), a flavonoid widely utilized in agricultural and pharmaceutical applications, has increasingly become a source of environmental concern. This study systematically evaluated the developmental toxicity of NGN in zebrafish embryos. Our results showed that NGN exposure caused dose-dependent increases in embryonic mortality and induced a range of developmental malformations, including reduced body length, impaired eye and ear development, and cardiac dysfunction. Behavioral analyses revealed significant deficits in locomotor activity and sensory responses at concentrations of 5 and 10 mg/L. Molecular assessments via RT-qPCR demonstrated that NGN disrupted the expression of multiple genes critical for cardiac (kcnh2a, kcnh2b, hand2, has2, myh7, tnnt2a), otic (col2a1a, sox9a, sox9b), liver (hhex, leg1.1), visual (gnat1, gnat2), apoptotic (bax, casp9, casp3), and neurodevelopmental (pomca, bdnf, gfap, mbpa, s100b) pathways. Notably, NGN at 10 mg/L inhibited apoptosis and altered liver function, whereas a concentration of 15 mg/L promoted apoptosis, and these results suggest that NGN may interfere with the developmental processes of zebrafish embryos through different mechanisms at low and high concentrations, exhibiting a non-monotonic dose-response relationship. These findings highlight the potential ecological hazards of NGN contamination in aquatic environments, emphasizing the need for stricter management and further research into its long-term and combined effects with other pollutants. Our research offers new perspectives into the molecular and phenotypic mechanisms of NGN toxicity and underscores the importance of comprehensive risk assessment for emerging environmental contaminants. Show less

2,4-Dichlorophenol (2,4-DCP) is a persistent and toxic metabolite derived from the degradation of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) and other chlorinated compounds, representing an emerging environmental concern. Despite evidence of its toxicity, its neurotoxic effects in adult organisms remain poorly understood. This study aimed to evaluate the behavioral, biochemical, and molecular responses of adult zebrafish (Danio rerio) following 14-day exposure to environmentally relevant (30 μg L Show less

Triclocarban (TCC), an antimicrobial agent used in personal care products, has been widely detected in aquatic ecosystems and has raised significant concerns for aquatic organisms and human health. This study aimed to investigate the neurotoxic effects of TCC exposure, a broad-spectrum bactericide, through behavioral, molecular, pathological, and metabolomic analyses. For this purpose, adult zebrafish were exposed to TCC at doses of 3, 10, and 30 μg/L for 96 h, and their brain tissues were removed. Subsequently, behavioral (anxiety and circadian rhythm tests), molecular (qPCR), histopathological, and metabolomic analyses were performed on these fish. The data obtained showed that TCC treatment increased anxiety-like behaviors in zebrafish and caused disruptions in the circadian rhythm. Additionally, it was determined that the expression levels of both core clock genes (Bmal and Gnat2) and genes associated with neuroplasticity, stress response, and neurotransmission (Bdnf, Crhr, 5-ht4, Ache) changed significantly in a dose-dependent manner compared to the control group. Additionally, it was observed that TCC increased degeneration and necrosis in the brain in parallel with the dose increase, while raising 8-OHdG and BDNF protein levels and decreasing NRF2 and SIRT1 protein levels. When metabolomic analysis data were evaluated, it was determined that TCC, especially at the highest dose, significantly altered metabolite levels. These results reveal that TCC, beyond being an environmental pollutant, may cause behavioral disorders and neurotoxic effects. Show less

Transcriptomics provides mechanistic insights into chemical toxicity and serves as a hypothesis-generating tool for prioritizing potential adverse outcomes. Here, we introduced a transcriptomics-guided outcome prediction (T-GOP) framework, a hypothesis-informed approach that uses transcriptomic enrichment to prioritize end points for targeted experimental validation. As a case study, the ecotoxicological effects of the PFOS alternative, sodium Show less

Microcystin-LR (MC-LR) is the most prevalent and toxic microcystin congeners, posing a significant threat to aquatic organisms as well as humans; however, its underlying toxic mechanisms remain incompletely elucidated. In this study, the negative impacts of MC-LR and the underlying mechanisms in zebrafish larvae were investigated. The results demonstrated that MC-LR could penetrate zebrafish larvae and induce developmental toxicity, characterized by reduced heart rate, decreased body length, and smaller eye area. H&E staining revealed that MC-LR exposure significantly reduced the thickness of retinal layers. qPCR analysis showed altered expression levels of phototransduction and retinoic acid metabolism related genes (rho, gnat1, gnat2, opn1sw1, opn1lw1, opn1mw1, rdh1, rbp4, cyp26a1, and aldh1a2). These findings suggest that MC-LR may disrupt retinal structure and impair normal visual function in larvae. Behavioral analyses indicated that MC-LR exposure weakened spontaneous movements in embryos and impaired swimming ability in larvae, potentially due to significant alterations in the levels of glutamate, γ-aminobutyric acid, and brain-derived neurotrophic factor. Additionally, MC-LR exposure reduced visuomotor responses, delayed reactions to external stimuli, and disrupted circadian rhythms, which may be attributed to altered expression levels of circadian rhythm-related genes (clock1a, bmal1a, per1b, cry1a, and per2), as well as changes in melatonin and arylalkylamine N-acetyltransferase 2 levels. Overall, these findings indicate that MC-LR exposure induces developmental neurotoxicity in zebrafish, and that impaired visual function and disrupted circadian rhythm may serve as key contributing factors to MC-LR-induced behavioral abnormalities, which warrant further emphasis in future ecological and health risk assessments. Show less

The transport of pharmaceutical compounds into aquatic ecosystems poses a significant environmental threat, particularly due to the presence of drugs that cannot be completely removed during wastewater treatment processes. Diclofenac (DCF), one of the most widely used nonsteroidal anti-inflammatory drugs worldwide, is among the pharmaceuticals frequently detected in aquatic environments due to its high consumption levels and persistence in the environment. It is known that this compound causes neurotoxicity, behavioral disorders, and physiological stress responses in aquatic organisms even at low concentrations. This study aimed to determine the effects of diclofenac exposure on oxidative stress, circadian rhythm, and behavioral parameters in zebrafish larvae. For this purpose, zebrafish embryos and early-stage larvae were exposed to DCF at concentrations of 0.5, 2.5, and 12.5 μg/L for 120 h. Subsequently, to investigate the effect of DCF on oxidative stress, SOD, CAT, GPX, and AChE enzyme activities and gene expression levels were analyzed. To examine its effects on behavior and circadian rhythm, thigmotaxis and locomotor activity analyses were performed. Additionally, to determine the molecular-level effects of behavioral changes, the expression levels of the bdnf, 5ht4, crhr, bmal1, per, and gnat2 genes were analyzed. Overall, our findings indicate that DCF affects behavioral activity, neurotransmitter metabolism, oxidative stress response, circadian rhythm, and retina-related molecular regulators in zebrafish larvae in a multilevel manner. These results highlight the potential risks of pharmaceutical contaminants on neurodevelopmental processes in aquatic ecosystems and demonstrate that even environmental doses can produce complex responses in biological systems. Show less

Alcohol consumption during pregnancy is a major public health concern, as prenatal exposure to ethanol can disrupt embryonic development and lead to Fetal Alcohol Spectrum Disorders (FASD). These disorders are characterized by a wide range of morphological, behavioral, and cognitive impairments, which variability across individuals is strongly influenced by genetic background and environmental conditions. Animal models, particularly zebrafish, offer a powerful tool to investigate how such factors modulate susceptibility to alcohol. In this study, we examined the effects of embryonic alcohol exposure in three zebrafish populations (AB, TU, and OB), assessing developmental parameters, behavior, and gene expression. Results showed that the OB population exhibited higher mortality and pronounced alterations in genes related to metabolism and neurotransmission; AB displayed reduced body and eye growth, along with increased social cohesion under alcohol exposure; while TU was more vulnerable to behavioral effects despite showing morphological resilience. Furthermore, the expression of key genes such as sox2, th1, drd1b, gabra1, and bdnf varied according to both population and alcohol concentration. These findings emphasize the relevance of genetic differences in modulating alcohol's impact and reinforce zebrafish as a valuable translational model for FASD research, paving the way for more refined diagnostic and therapeutic approaches. Show less

Sensory neurotoxicity involves damage to the sensory nerves, often resulting from exposure to chemicals, medications, toxins, infections, or neurological disorders. Benzalkonium chloride (BKC) is a widely used quaternary ammonium compound with antiseptic properties, commonly present in pharmaceuticals, household products, and cosmetics. While the potential neurotoxicity of BKC has been previously explored in ocular and nasal epithelia, its impact on other sensory systems and the underlying mechanisms remain largely unclear. In this study, we used zebrafish (Danio rerio) embryos to assess the developmental neurotoxicity of BKC. Embryonic exposure to 0.72, 1.28, and 2.24 mg/L BKC led to dose-dependent impairments in mechanosensory hair cells, reduced startle responses, and heightened nociceptive sensitivity upon noxious stimulation. BKC exposure induced pronounced oxidative stress, evidenced by increased reactive oxygen species levels, reduced antioxidant enzyme activity, and altered expression of redox-regulating genes. Moreover, BKC significantly upregulated inflammatory and pain-associated genes, including tnfa, il1b, cox2, bdnf, and trpa1b. Expression profiling of hair cell differentiation markers revealed increased pou4f3 and decreased tmc2a/tmc2b, suggesting that BKC disrupts both terminal differentiation and mechanotransduction processes in sensory hair cells. Collectively, these findings uncover a novel mechanistic link between oxidative stress, impaired hair-cell maturation, and sensory dysfunction, offering new insights into the mechanisms underlying BKC-induced sensory neurotoxicity. This study emphasizes the ecological and toxicological relevance of quaternary ammonium compounds in aquatic environments. Show less