bims-aporos 2018-09-02 papers

Issue of 2018‒09‒02
three papers selected by
Gavin McStay
Staffordshire University

Toxicol In Vitro. 2018 Aug 23. pii: S0887-2333(18)30484-3. [Epub ahead of print]

N-acetylcysteine prevents cytotoxic effects induced by man-made mineral fibers in a human bronchial epithelial cell line.

Min Zhang, HaiLing Xia, Min Yu, LiJin Zhu, Li Ju, JunQiang Chen, JiaJun Zhao, Yun Xiao, Kun Chen.

Man-made mineral fibres (MMMFs) such as glass wool (GW), rock wool (RW) and refractory ceramic fibres (RCFs) are widely used as substitutes of asbestos. The present study aimed to investigate the cytotoxic effects on human bronchial epithelial cells (BEAS-2B) exposed to GW1, RW1 and RCF2, considering their properties similar to that of asbestos. We assessed cell viability; cell morphological changes; apoptotic rate; DNA damage; reactive oxygen species (ROS) generation; activities of caspase-3, caspase-8 and caspase-9; and expression levels of FasL, phosphorylated p38, and total p38 MAPK proteins. N-acetyl-l-cysteine (NAC) was used as an ROS scavenger. We observed that MMMFs, especially RCF2, evidently changed cellular morphology, promoted DNA damage, and induced apoptosis. In addition, the cytotoxicities of MMMFs were dependent on ROS generation, and NAC could decrease their toxicity. Furthermore, our results showed that apoptosis induced by MMMFs was mediated by the mitochondrial apoptotic pathway and Fas death receptor pathway. Moreover, the p38 MAPK signalling pathway was also involved in the cytotoxicities of MMMFs. NAC exerts a protective effect against apoptosis and DNA damage induced by GW1, RW1 and RCF2. This study provides important implications for understanding the potential toxic effects of GW1, RW1 and RCF2 exposure; it also indicates that NAC may prevent respiratory diseases induced by exposure to MMMFs.

Keywords: Apoptosis; DNA damage; Mineral fibres; Reactive oxygen species

DOI: https://doi.org/10.1016/j.tiv.2018.08.012

J Cell Physiol. 2018 Aug 26.

Ketamine induces reactive oxygen species and enhances autophagy in SV-HUC-1 human uroepithelial cells.

Zhengfei Shan, Liqin Wei, Shengqiang Yu, Shanling Jiang, Yue Ma, Chengjun Zhang, Jiantao Wang, Zhenli Gao, Fengchun Wan, Guimin Zhuang, Jitao Wu, Dongfu Liu.

This study was aimed at exploring the underlying mechanisms of ketamine in the SV-40 immortalized human ureteral epithelial (SV-HUC-1) cells. The viability and apoptosis of SV-HUC-1 cells treated with 0.01, 0.1, and 1 mM ketamine were respectively detected via cell counting kit-8 (CCK-8) assay and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) staining. Reactive oxygen species (ROS) level was measured through ROS probe staining. Apoptosis-related proteins (B-cell lymphoma 2 [Bcl-2] and Bax) and autophagy-associated proteins (light chain 3-I [LC3-I] and LC3-II) were determined by western blot or immunofluorescent assay. Additionally, transmission electron microscopy (TEM) was used to evaluate the formation of autophagosomes. After cotreatment of 3-methyladenine (3-MA) or N-acetyl-l-cysteine (NAC), the biological functions of SV-HUC-1 cells were analyzed to determine the association of ROS with cell viability and autophagy. CCK-8 assay and TUNEL staining indicated that ketamine effectively decreased the viability of SV-HUC-1 cells and accelerated apoptosis of SV-HUC-1 cells through regulating the expression level of IKBα (phospho), nuclear factor кB (P65), Bcl-2, and Bax proteins. Enhanced ROS production was also confirmed in ketamine-treated SV-HUC-1 cells treated with ketamine. Ketamine-induced autophagosomes in SV-HUC-1 cells were observed by means of TEM, and increased levels of LC3 II/I ratio and Beclin 1 were examined through western blot and immunofluorescent assay. Furthermore, ketamine exerted effects on SV-HUC-1 cells in a dose-dependent and time-dependent manner. Additionally, cotreatment of NAC with 3-MA significantly attenuated the ROS level and suppressed the cell autophagy. Ketamine promoted SV-HUC-1 cell autophagy and impaired the cell viability of SV-HUC-1 cells by inducing ROS.

Keywords: SV-HUC-1; autophagy; ketamine; reactive oxygen species

DOI: https://doi.org/10.1002/jcp.27094

Pharmacol Rep. 2018 May 17. pii: S1734-1140(17)30680-1. [Epub ahead of print]70(5): 1040-1046

Protective effects of curcumin on acrolein-induced neurotoxicity in HT22 mouse hippocampal cells.

Lan-Ying Shi, Li Zhang, Hui Li, Tao-Li Liu, Ji-Cai Lai, Zhi-Bing Wu, Jian Qin.

BACKGROUND: Aging is one of the most important inevitable risk factors of Alzheimer disease (AD). Oxidative stress plays a critical role in the process of aging. Curcumin has been proposed to improve neural damage, especially neurodegenerative injury, through its antioxidant and anti-inflammatory properties. Therefore, we investigated the effects of curcumin on acrolein-induced AD-like pathologies in HT22 cells.METHODS: HT22 murine hippocampal neuronal cells were treated with 25 μM acrolein for 24 h with or without pre-treating with curcumin at the selected optimum concentration (5 μg/mL) for 30 min. Cell viability and apoptosis were measured by CCK8 assay and flow cytometric analysis. Levels of glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) were detected by a GSH assay kit or commercial assay kits, respectively. Alterations in the expression of BDNF/TrkB and key enzymes involved in amyloid precursor protein (APP) metabolism were assessed by western blotting.
RESULTS: Data showed that curcumin significantly reversed acrolein-induced oxidative stress indicated by depletion of GSH and SOD, and elevation of MDA. The findings also suggested curcumin's potential in protecting HT22 cells against acrolein through regulating the BDNF/TrkB signaling. In addition, acrolein-induced reduction in A-disintegrin and metalloprotease, and the increase of amyloid precursor protein, β-secretase, and receptor for advanced glycation end products were reversed either, and most of them were nearly restored to the control levels by curcumin.
CONCLUSION: These findings demonstrate the protective effects of curcumin on acrolein-induced neurotoxicity in vitro, which further suggests its potential role in the treatment of AD.

Keywords: Acrolein; Alzheimer disease; BNDF/TrkB; Curcumin

DOI: https://doi.org/10.1016/j.pharep.2018.05.006