1,2-Dichloroethane (1,2-DCE) is a widely used chlorinated organic toxicant, but little is known about the cerebellar dysfunction induced by excessive exposure to it. To uncover 1,2-DCE-induced neurotoxicity in cerebellar granular cells (CGCs), and to investigate the underlying mechanisms, we explored this, both in vitro and in vivo. Our findings showed significant cell viability inhibition in human CGCs (HCGCs) treated with 1,2-DCE. Flow cytometry and mitochondrial membrane potential analyses discovered an increase in apoptotic-mediated cell death in HCGCs after 1,2-DCE treatment. This HCGC apoptosis was involved in the increases of protein expression in Cytochrome c, Caspase-3, Bad, Bim, transformation related protein 53, Caspase-8, tumor necrosis factor-α, and Survivin. Quantitative real-time PCR (qPCR) and western blot confirmed the increases in Cytochrome c, Caspase-3, cleaved Caspase-3, and Bad in HCGCs after 1,2-DCE treatment. Bax inhibitor peptide V5 rescued 1,2-DCE-induced HCGC apoptosis. Furthermore, 80 CD-1 male mice were exposed to 1,2-DCE by inhalation at 0, 100, 350, and 700 mg/m for 6 h/day for 4 weeks. An open field test found abnormal neurobehavioral changes in the mice exposed to 1,2-DCE. Histopathological examination showed significantly shrunken and hypereosinophilic cytoplasm with nuclear pyknosis in mouse CGCs from the 700 mg/m 1,2-DCE group. TdT-mediated dUTP nick-end labeling assay verified significant increases in apoptotic positive cells in the mouse CGCs after 1,2-DCE exposure. We confirmed the increases in the expressions of Cytochrome c, Caspase-3, cleaved Caspase-3 and Bad in the mice exposed to 1,2-DCE. These findings suggest that 1,2-DCE exposure can induce CGC apoptosis and cerebellar dysfunction, at least in part, through mitochondrial pathway.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.toxlet.2020.01.004 | DOI Listing |
Toxicol Res (Camb)
December 2024
Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Khorasan Razavi, Mashhad, Azadi Square, 9177948954, Iran.
Objective: Alzheimer's disease (ad) is a progressive and degenerative disorder of the central nervous system that is associated with cognitive and memory impairment. The main factors which have been implicated in neurodegeneration of ad are oxidative stress and cholinergic neurons dysfunction. Here, we examined the effects of auraptene, a novel acetylcholinesterase (AChE) inhibitor, on hydrogen peroxide (HO)-induced cell death in PC12 cells.
View Article and Find Full Text PDFWorld J Oncol
December 2024
Department of Radiation Oncology, University of Kansas Medical Center, Kansas City, KS, USA.
Background: Bladder cancer patients unable to receive cystectomy or who choose to pursue organ-sparing approach are managed with definitive (chemo)radiotherapy. However, this standard of care has not evolved in decades and disease recurrence and survival outcomes remain poor. Identifying novel therapies to combine with radiotherapy (RT) is therefore paramount to improve overall patient outcomes and survival.
View Article and Find Full Text PDFFood Chem
December 2024
State Key Laboratory of Marine Food Processing & Safety Control, College of Food Science and Engineering, Ocean University of China, No. 1299, Sansha Road, Qingdao, Shandong Province 266404, China; Qingdao Marine Science and Technology Center, Qingdao, Shandong Province 266235, China. Electronic address:
Apoptosis occurs in the myocyte of fish postmortem storage. Based on the important role of mitochondrial lipid molecules in regulating apoptosis, the study aims to investigate the potential impact of mitochondrial lipids on apoptosis and quality deterioration of large yellow croaker. A total of 1079 lipid molecule species in 13 classes were identified in mitochondria.
View Article and Find Full Text PDFRes Pharm Sci
October 2024
Department of Physiology and Pharmacology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, I.R. Iran.
Background And Purpose: Neuropathy is one of the common complications of diabetes mellitus. This study aimed to determine the analgesic and antiapoptotic effects of the aqueous extract of L. (Ach) in rats with experimental painful diabetic neuropathy by behavioral and molecular procedures.
View Article and Find Full Text PDFSci Total Environ
December 2024
State Environmental Protection Key Laboratory of Environmental Pollution Health Risk Assessment, South China Institute of Environmental Sciences, Ministry of Ecology and Environment, Guangzhou 510655, China.
Microplastics (MPs) are ubiquitous in the environment and have been identified as a potential threat to ecosystems. However, the mechanisms of toxicity of modified MPs remain unknown. This study investigated the developmental toxicity of amino-modified polystyrene microplastics (PS-NH) with environmentally relevant concentrations ranging from 0.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!