Developmental neurotoxicity and toxic mechanisms induced by olaquindox in zebrafish

Abstract

Olaquindox (OLA) has been widely used as an animal feed additive in China for decades; however, its toxicity and toxic mechanisms have not been well investigated. In this study, the developmental neurotoxicity and toxic mechanisms of OLA were evaluated in zebrafish. Zebrafish embryos were exposed to different concentrations of OLA (25-1,000 mg/L) from 6 to 120 hours post fertilization (hpf). OLA exposure resulted in many abnormal phenotypes in zebrafish, including shortened body length, notochord degeneration, spinal curvature, brain apoptosis, damage of axon and peripheral motor neuron, and hepatotoxicity. Interestingly, OLA increased zebrafish spontaneous tail coiling, while reduced locomotor capacity. Quantitative polymerase chain reaction (Q-PCR) showed that the expression levels of nine marker genes for nervous system functions or development, namely, α1-tubulin, glial fibrillary acidic protein (gfap), myelin basic protein (mbp), synapsinII a (syn2a), sonic hedgehog a (shha), encoding HuC (elavl3), mesencephalic astrocyte-derived neurotrophic factor (manf) growth associated protein 43 (gap43), and acetylcholinesterase (ache) were all down-regulated significantly in zebrafish after treated with OLA. Besides, the antiapoptotic and pro-apoptotic genes bcl-2/bax ratio was reduced. These results show that OLA exposure could cause severe developmental neurotoxicity in the early stages of zebrafish life and OLA might induce neurotoxicity by inhibiting the expression of neuro-developmental genes and promoting apoptosis.

Qilong Capsule Alleviated MPTP‐Induced Neuronal Defects by Inhibiting Apoptosis, Regulating Autophagy in Zebrafish Embryo Model

“…Bdnf and gdnf genes increased the survival of dopaminergic neurons and promoted neuroprotection and nerve regeneration [39,40] . The protein encoded by mbp gene is important for maintaining myelin structure, and the loss of the myelin sheath leads to a variety of neurological diseases [41,42] . In this study, the expression of bdnf , gdnf and mbp , were downregulated by MPTP, and QLC prevented neuron loss, reduced inflammatory responses, and promoted the development of dopaminergic neurons.…”

Developmental toxicity of the emerging contaminant cyclophosphamide and the integrated biomarker response (IBRv2) in zebrafish

“…The available chemotherapeutic drug-toxicity on FET study also reported that LPO could also induce apoptosis. 79 The AO study reveals that CP could cause 80 Inhibition of AChE activity signies the disruption of neurotransmission of CP in zebrash embryos/ larvae. Chemicals could cause neurotoxicity by binding and inducing phosphorylation on the serine hydroxyl group at the active site-esterication of AChE during embryonic development.…”

“…AChE plays a significant role in embryonic neuronal and muscle development. 80 Inhibition of AChE activity signifies the disruption of neurotransmission of CP in zebrafish embryos/larvae. Chemicals could cause neurotoxicity by binding and inducing phosphorylation on the serine hydroxyl group at the active site-esterification of AChE during embryonic development.…”

The mechanism and effects of remdesivir‐induced developmental toxicity in zebrafish: Blood flow dysfunction and behavioral alterations

“…Zebrafish have a wide range of applications in ecotoxicology, pharmaceutical toxicology and developmental biology (Baraban et al, 2013; Y. Chen et al, 2021; Gu et al, 2021; Guo et al, 2021). Moreover, they are perfect animal models for observing the effects of drugs on embryo development, cardiogenesis, neurobehavior, and blood flow compared with other vertebrate models because they exhibit in vitro fertilization, in vitro development, body transparency and rapid growth and development of physiological functions (Chen et al, 2021; Serbanovic‐Canic et al, 2017).…”

“…Moreover, the zebrafish genome has been sequenced and is highly similar to the human genome (Meng et al, 2020). Due to these obvious advantages, zebrafish have been widely used in drug toxicology and safety evaluation, ecotoxicology, chemical toxicity, new drug screening, a good model studied for human disease and developmental biology research in recent years (Baraban et al, 2013; Chen et al, 2021; Gu et al, 2021; Guo et al, 2021).…”