Search

Valproic acid (VPA) is a widely prescribed antiepileptic drug with various medicinal efficacies. Accumulated evidence implied that prenatal exposure to VPA is highly associated with autism spectrum disorder (ASD). In this study, the zebrafish were exposed to a set of VPA concentrations (0, 5, 10, 20, 40, 80, 160, 320, 640, 1280, and 2560 μM) at 5 h post fertilization (hpf) to 120 hpf. The adverse effects of VPA were extensively studied through the evaluations on the mortality, heartbeats, spontaneous tail coiling, and hatching rate. Morphological observations were conducted at 120 hpf, following the exposure termination. Basic locomotor responses and anxiety-like behavioral alterations evaluated for behavioral impairments are the hallmark feature of ASD. The exposure to VPA at teratogenic concentrations reduced the aforementioned parameters in a dose-dependent manner (p ≤ .05). At the selected nonteratogenic concentrations of VPA, the treated larvae demonstrated profound alterations of basic locomotor responses. No significant changes of anxiety and thigmotactic behaviors were observed on the VPA-treated fish compared to the control (p ≥ .005). This study depicted that embryonic zebrafish exposure to VPA produced significant toxicity and teratogenicity effects as well as the alterations of basic behavioral responses. Overall, this study provides a fundamental insight of the toxicity effects at morphological and behavioral levels to facilitate the understanding of ASD mechanisms at different molecular levels. [ABSTRACT FROM AUTHOR]

Christia vespertilionis or butterfly wings is a traditional medicinal plant used to treat, among others, colds and bronchitis. The plant was also reported to be a remedy for cancer, with several products based on the plant becoming commercially available, raising some safety concerns on its consumption. The present study was carried out to assess the toxic and teratogenic effects of the plant on the embryonic development of zebrafish (Danio rerio) as the animal model. Zebrafish embryos were exposed to 50, 100, 200, 400, and 800 μg/mL of the methanolic leaf extract of C. vespertilionis, starting from 5 to 120 hours post-fertilization (hpf). The median lethal concentration (LC50) value of the extract was determined to be 419.84 μg/mL, which is within the safety limit stipulated by the Organisation for Economic Co-operation and Development (OECD) guideline. However, results from the teratogenicity evaluation revealed multiple signs of developmental defects in embryos exposed to 200 μg/ mL and higher concentrations of the extract. The magnitude of the defects was observed to be concentration-dependent. Moreover, no hatching and spontaneous movement of tail coiling were observed at 400 and 800 μg/mL concentrations due to the delayed growth and early mortality, respectively. A significant reduction in heartbeat rate was also reported for the surviving embryos at the 400 μg/ mL test concentration. The present study has provided preliminary results on the potentially toxic and teratogenic effects of the extract at high concentrations. [ABSTRACT FROM AUTHOR]

Valproic acid (VPA) is a widely prescribed antiepileptic drug with various medicinal efficacies. Accumulated evidence implied that prenatal exposure to VPA is highly associated with autism spectrum disorder (ASD). In this study, the zebrafish were exposed to a set of VPA concentrations (0, 5, 10, 20, 40, 80, 160, 320, 640, 1280, and 2560 μM) at 5 h post fertilization (hpf) to 120 hpf. The adverse effects of VPA were extensively studied through the evaluations on the mortality, heartbeats, spontaneous tail coiling, and hatching rate. Morphological observations were conducted at 120 hpf, following the exposure termination. Basic locomotor responses and anxiety-like behavioral alterations evaluated for behavioral impairments are the hallmark feature of ASD. The exposure to VPA at teratogenic concentrations reduced the aforementioned parameters in a dose-dependent manner (p ≤ .05). At the selected non-teratogenic concentrations of VPA, the treated larvae demonstrated profound alterations of basic locomotor responses. No significant changes of anxiety and thigmotactic behaviors were observed on the VPA-treated fish compared to the control (p ≥ .005). This study depicted that embryonic zebrafish exposure to VPA produced significant toxicity and teratogenicity effects as well as the alterations of basic behavioral responses. Overall, this study provides a fundamental insight of the toxicity effects at morphological and behavioral levels to facilitate the understanding of ASD mechanisms at different molecular levels., (© 2023 Wiley Periodicals LLC.)