title: Contributions of altered permeability of intestinal barrier and defecation behavior to toxicity formation from graphene oxide in nematode Caenorhabditis elegans.
abstract: Graphene oxide (GO) has been extensively studied for potential biomedical applications. Meanwhile, potential GO toxicity arises in both biomedical applications and non-biomedical products where environmental exposures may occur. In the present study, we examined the potential adverse effects of GO and the underlying mechanism using nematode Caenorhabditis elegans as the assay system. We compared the in vivo effects of GO between acute exposure and prolonged exposure, and found that prolonged exposure to 0.5-100 mg L(-1) of GO caused damage on functions of both primary (intestine) and secondary (neuron and reproductive organ) targeted organs. In the intestine, ROS production was significantly correlated with the formation of adverse effects on functions of both primary and secondary targeted organs. GO could be translocated into intestinal cells with loss of microvilli, and distributed to be adjacent to or surrounding mitochondria. Prolonged exposure to GO resulted in a hyper-permeable state of the intestinal barrier, an increase in mean defecation cycle length, and alteration of genes required for intestinal development and defecation behavior. Thus, our data suggest that prolonged exposure to GO may cause potential risk to environmental organisms after release into the environment. GO toxicity may be due to the combinational effects of oxidative stress in the intestinal barrier, enhanced permeability of the biological barrier, and suppressed defecation behavior in C. elegans.
authors.affiliation: Key Laboratory of Environmental Medicine Engineering in Ministry of Education, Medical School of Southeast University, Nanjing 210009, China. dayongw@seu.edu.cn.
authors.forename: Qiuli
authors.initials: Q
authors.lastname: Wu
authors.forename: Li
authors.initials: L
authors.lastname: Yin
authors.forename: Xing
authors.initials: X
authors.lastname: Li
authors.forename: Meng
authors.initials: M
authors.lastname: Tang
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.forename: Dayong
authors.initials: D
authors.lastname: Wang
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000502:physiology*; D003672:Defecation; D004781:Environmental Exposure; D006108:Graphite / Q000737:chemistry / Q000633:toxicity*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010087:Oxides / Q000737:chemistry; D010539:Permeability / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D010087:Oxides; D017382:Reactive Oxygen Species; D006108:Graphite