Toxic effects of combined treatment of 1,2‐dichloroethane and ethanol on mouse brain and the related mechanisms

Abstract

The aim of this study was to explore the mechanisms of brain damage induced by the combined treatment of mice with 1,2-dichloroethane (1,2-DCE) and ethanol. Mice were divided into control group; 1,2-DCE-intoxicated group; ethanol-treated group; and low-, medium-, and high-dose combined treatment groups. Histological observations along with brain organ coefficients and water content were used to measure the brain damage directly and indirectly. The levels of nonprotein sulfhydryls, malondialdehyde (MDA), and superoxide dismutase activity were used as parameters to evaluate oxidative stress in the brain. Protein and messenger RNA (mRNA) levels of cytochrome P450 2E1 (CYP2E1), zonula occludens-1 (occludin and zo-1), aquaporin-4 (AQP4), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase (HO)-1, and the γ-glutamyl cysteine synthetase catalytic and modulatory subunits (γ-GCSc, GR, and γ-GCSm) in the brain were examined by Western blot analysis and quantitative polymerase chain reaction analysis, respectively. Effects of the combined treatment of 1,2-DCE and ethanol were evaluated by analysis of variance with a factorial design. The results suggested that combined exposure to ethanol and 1,2-DCE synergistically increased CYP2E1 protein and mRNA levels, accelerated the metabolism of ethanol and 1,2-DCE in the brain tissue, induced high production of reactive oxygen species (ROS), and increased MDA levels, thereby damaging the blood-brain barrier and causing obvious pathological changes in brain tissue. However, the increased level of ROS activated the Nrf2 signal transduction pathway, promoting the expression of HO-1 and glutathione-related antioxidant enzymes in the brain to protect the cells from oxidative damage.

The Effectiveness of Hawthorn (Ws-1442 Standardized Crataegus oxycantha Extract) Against Alcohol-Induced Brain Injury In Rat; Its Underlying Potential Mechanisms

“…A new suggestion in our study was developed in favor of SCE in rats with brain injury undergoing alcohol detoxi cation. The evidence reviewed supported the continuation of a recommendation the use of the antioxidants for the prevention of traumatic brain damages in patients receiving high-dose alcohol [37].…”

Rac1/Wave2/Arp3 Pathway Mediates Rat Blood-Brain Barrier Dysfunction under Simulated Microgravity Based on Proteomics Strategy

“…Oxidative stress activates MMP-9, which contributes to the breakdown of ECM and directly degrades TJs proteins, leading to BBB damage [ 43 ]. One study suggested that the increased MDA levels induced a dramatic reduction of TJs-associated proteins, thereby disrupting rat BBB [ 44 ]. Another study discovered that increased MDA content and decreased SOD activity in rat brain tissue significantly induced BBB hyperpermeability in the rat ischemia-reperfusion injury model [ 45 ].…”

Identification and Risk Assessment of Priority Control Organic Pollutants in Groundwater in the Junggar Basin in Xinjiang, P.R. China

“…However, due to its slow volatilization in the vadose zone, 1,2-dichloroethane in the vadose zone tends to migrate downward into groundwater and subsequently move downstream with the groundwater flow, causing persistent organic pollution [81]. As for humans and animals, long-term contact with and/or intake of 1,2dichloroethane-containing groundwater could cause cranial nerve injury, gene mutations and cancer [82,83]. Once 1,2-dichloroethane-containing groundwater enters into and accumulates in plants/crops, the photosynthesis and growth of the plants/crops will be inhibited [84].…”