期刊
TOXICOLOGY
卷 474, 期 -, 页码 -出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.tox.2022.153226
关键词
Di(2-ethylhexyl) Phthalate; Microplastics; Oxidative stress; Apoptosis; Necroptosis
DEHP and MPs exposure alone or in combination can induce skeletal muscle cell injury by activating oxidative stress and down-regulating the PI3K/AKT/mTOR signaling pathway, and the combined exposure group exhibits higher toxicity.
The plastic decomposition product microplastics (MPs) and the plastic additive Di (2-ethylhexyl) phthalate (DEHP) in the environment can damage various organs of the organism by inducing oxidative stress. The PI3K/AKT/mTOR signaling pathway participate in toxin-induced apoptosis and necroptosis. However, the effects of DEHP/MPs alone and combined exposure on skeletal muscle cell injury in mice and the role of PI3K/AKT/mTOR axis remain unclear. To investigate the effect of DEHP or/and MPs on skeletal muscle in mice and its possible toxicological mechanism, 60 mice were randomly divided into control group, DEHP group (DEHP 200 mg/kg dissolved in 50 mL corn oil mixed with 2.5 kg diet), MPs group (10 mg/L MPs in drinking water) and combined exposure group. In vitro, C2C12 cells were exposed to DEHP 600 mu M/MPs 800 mu M alone or in combination for 24 h. The results showed that DEHP/MPs exposure alone or in combination increased MDA content, decreased activities of CAT, T-AOC, SOD and GSH-Px, increased mRNA and protein expressions of Caspase-3, BAX, RIPK1, RIPK3 and MLKL, and decreased BCL-2 expression. The expression of PI3K/AKT/mTOR signaling pathway was significantly down-regulated. All the above results showed that the combined exposure group was more toxic, and similar experimental results were obtained by DEHP/MPs exposure test of C2C12 cells in vitro. It is suggested that DEHP/MPs can induce apoptosis and necroptosis by activating oxidative stress and down-regulating PI3K/AKT/mTOR pathway. This study provides new evidence for clarifying the possible mechanism of toxicity of DEHP and MPs to skeletal muscle of mice.
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