Di-2-ethylhexyl phthalate (DEHP) induces apoptosis of mouse HT22 hippocampal neuronal cells via oxidative stress

Abstract

Di-2-ethylhexyl phthalate (DEHP) has been widely used as a plasticizer in industry and can affect memory; however, the underlying mechanism remains unclear. In the present study, mouse HT22 cells, an immortalized hippocampal neuronal cell line, was utilized as an in vitro model. We showed that DEHP dramatically inhibited cell viability and increased lactate dehydrogenase (LDH) release from the cells in a dose-dependent manner, suggesting that DEHP could cause cytotoxicity of mouse HT22 cells. The protein levels of cleaved Caspase-8, cleaved Caspase-3, and Bax markedly increased in the DEHP-treated cells, whereas there was a significant decrease in the Bcl-2 protein level, implying that DEHP could induce apoptosis of mouse HT22 cells. DEHP exposure significantly increased the content of malondialdehyde, whereas it markedly decreased the level of glutathione and the activities of glutathione peroxidase and superoxide dismutase, suggesting that DEHP induced oxidative stress of the cells. Compared with the DEHP-treated group, the inhibition of cell viability and the release of LDH were rescued in the N-acetyl-l-cysteine plus DEHP group. Furthermore, inhibition of oxidative stress could rescue the induction of apoptosis by DEHP. Collectively, our results indicated that DEHP could induce apoptosis of mouse HT22 cells via oxidative stress.

Taurine ameliorates cytotoxic effects of Di(2‐ethylhexyl) phthalate on Leydig cells

“…In parallel with our findings, Tu et al. (2020) have shown that DEHP induces apoptosis in the HT22 cells (a hippocampal cell line) via enhancing Bax expression, caspase‐3 activity and MDA contents and reducing Bcl‐2 expression and SOD activity. DEHP‐induced oxidative stress through increasing ROS level in spermatocytes of the rats (Kasahara et al., 2002).…”

TFEB ameliorates DEHP‐induced neurotoxicity by activating GAL3/TRIM16 axis dependent lysophagy and alleviating lysosomal dysfunction

“…11 This finding aligns with the work of Tu et al, who reported elevated levels of apoptotic proteins such as caspase-3 and Bax in HT22 cells following DEHP exposure. 12 In addition, we found that the percentage of apoptosis in neuronal cells was also significantly increased by DEHP exposure by flow cytometry, a method most commonly used when assessing the level of apoptosis, 35 which further supports our results.…”

Di(2‐ethylhexyl) phthalate and microplastics cause necroptosis and apoptosis in hepatocytes of mice by inducing oxidative stress

“…A large number of studies have confirmed that oxidative stress can further cause apoptosis. Tu et al showed that DEHP could lead apoptosis of mouse HT22 hippocampal neurons through oxidative stress 56 . The apoptosis induced by DEHP of mouse NE‐4C neural stem cells is also related to oxidative stress.…”

“…Tu et al showed that DEHP could lead apoptosis of mouse HT22 hippocampal neurons through oxidative stress. 56 The apoptosis induced by DEHP of mouse NE-4C neural stem cells is also related to oxidative stress. MPs can induce hepatocyte apoptosis and abnormal glycolysis flux through ROS driven calcium overload.…”