Tuning Toxicity Profiles of Graphene Oxide Through Imidazole-Oxime Modification: Zebrafish as a Model System

Abstract

The increasing use of nanotechnology, especially in agriculture and the food industry, has raised concerns about the possible adverse effects of nanomaterials (NMs) on human health and the environment. This study investigates the effects of synthesized graphene oxide (GO) and its derivatives on zebrafish exposed for 96 hr, focusing on morphological changes in brain tissue, histopathology, and immunofluorescent markers such as 8-hydroxy-2'-deoxyguanosine (8-OHdG) and nucleolar protein 10 (NOP10). Exposure to GO resulted in malformations, DNA damage, and increased NOP10 expression, and it reduced hatching and survival rates. Our results demonstrated that exposure to GO, graphene oxide-oxime (GO-OX), and OX exerted dose-dependent inhibitory effects on hatching and promoted malformations in zebrafish larvae. Histopathological analysis revealed that higher doses led to more pronounced tissue damage, with GO 50 causing severe degeneration and necrosis, while high doses of GO-OX and OX resulted in moderate tissue changes. This was further supported by the increased expression levels of 8-OHdG (marker of oxidative DNA damage) and NOP10 (marker of nucleolar stress), which aligns with the histopathological findings and confirms the neurotoxic effects. Notably, GO-OX treatments consistently mitigated both morphological and neurotoxic effects at all doses, suggesting that oxime functionalization reduces the inherent toxicity of GO. In contrast, treatment with different concentrations of GO-OX derivatives mitigated these adverse effects, reducing them to mild or moderate levels.