Developmental neurotoxicity and immunotoxicity induced by graphene oxide in zebrafish embryos

Abstract

Graphene oxide (GO) has emerged as the worldwide promising candidate for biomedical application, such as for drug delivery, bio-sensing and anti-cancer therapy. This study was focused on the zebrafish and RAW264.7 cell line as in vivo and in vitro models to assess the potential developmental neurotoxicity and immunotoxicity of GO. No obvious acute developmental toxicity was observed upon treatments with 0.01, 0.1, and 1 μg/mL GO for five consecutive days.However, decreased hatching rate, increased malformation rate, heart beat rate and hypoactivity of locomotor behavior were detected when exposed to 10 μg/mL GO. Also, RT-PCR analysis revealed that expressions of genes related to the nervous system were up-regulated. The potential risk of GO for developmental neurotoxicity may be ascribed to the high level of oxidative stress induced by high concentration of GO. Most importantly, the mRNA levels of immune response associated genes, such as interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNFα), interferon-γ (IFN-γ) were significantly increased under environmental concentration exposure. The activation of pro-inflammatory immune response was also observed in macrophage cell line. Taken together, our results demonstrated that immunotoxicity is a sensitive indicator for assessment of bio-compatibility of GO. K E Y W O R D S embryotoxicity, graphene oxide, oxidative stress, Raw264.7 cells, zebrafish

Assessment of reproductive and developmental effects of graphene oxide on Japanese medaka (Oryzias latipes)

“…However, higher concentration showed significant impact on embryo mortality, hatching, and disorder in cardiovasculature (Bageppagari et al, 2019). Exposure of zebrafish embryos to GO for five consecutive days did not induce acute developmental toxicity, however, hatching and locomotor behavior were altered (Yang et al, 2019). Moreover, genes related to nervous and immune systems were upregulated (Yang et al, 2019).…”

“…Exposure of zebrafish embryos to GO for five consecutive days did not induce acute developmental toxicity, however, hatching and locomotor behavior were altered (Yang et al, 2019). Moreover, genes related to nervous and immune systems were upregulated (Yang et al, 2019). Proteomic analysis in zebrafish larvae identified down-regulation of several oxidative stress-related proteins by GO (Zou et al, 2018;Dasmahapatra et al, 2019).…”

“…The toxicity of GO in fish, especially in zebrafish (Danio rerio) was found to be concentration-dependent (Bageppagari et al, 2019;Dasmahapatra et al, 2019;Yang et al, 2019), and did not affect embryonic development at lower concentrations. However, higher concentration showed significant impact on embryo mortality, hatching, and disorder in cardiovasculature (Bageppagari et al, 2019).…”

How macrophages respond to two-dimensional materials: a critical overview focusing on toxicity

“…In addition, the content of malondialdehyde, glutathione and superoxide dismutase increased in a dose-dependent manner following treatment with GO. [107] The lateral size of GO is also important in cytokine expression. For example, small and thin GO (lateral dimensions ranged between 50 nm and 2 µm) dose-dependently inhibited the release of IL-1β and IL-6 but not TNF-α, while NLRP3 inflammasome and caspase-1 activation were not affected.…”

Graphene and Reproduction: A Love-Hate Relationship

“…As has been inferred from the scientometric analysis, the majority of the studies conducted to date regarding graphene and GDMs and reproduction have aimed to analyse the toxicological events involving the reproductive function, a powerful approach that allows examining not only the detrimental effects caused to the single individual but also the effects left in bequest to the offspring. In that way and from 2014 (see Figure 1), some researchers have focused their works on elucidating the effects induced directly to the developing embryos in different species [67][68][69][70]. Zebrafish, an aquatic vertebrate useful to assess toxicity in aquatic environments, is one of the species most frequently used to this aim.…”