Cellular and molecular etiology of hepatocyte injury in a murine model of environmentally induced liver abnormality.
Cellular and molecular etiology of hepatocyte injury in a murine model of environmentally induced liver abnormality.
复制标题
环境诱导的肝脏异常模型中肝细胞损伤的细胞和分子病因。
DOI：
10.4314/ovj.v6i3.1
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发表时间：
2016
影响因子：
1.2
通讯作者：
Bennour EM
中科院分区：
文献类型：
--
作者：
Al-Griw MA;Alghazeer RO;Al-Azreg SA;Bennour EM
接触各种环境物质与人类和啮齿动物的许多生物细胞系统呈负相关。三氯乙烷 (TCE) 是一种普遍存在的环境毒物，被大量用作溶剂、金属脱脂剂、化学中间体和消费品的成分。这增加了人类通过皮肤、吸入和口服途径接触这些化合物的可能性。本体内研究旨在利用小鼠模型研究早期暴露于 TCE 引起的肝脏异常的可能细胞和分子病因。结果显示肝脏重量显着增加。组织病理学检查显示 TCE 诱导的肝毒性，表现为中央静脉和血窦严重充血以及白细胞浸润。还鉴定了有丝分裂图和细胞凋亡变化，例如染色质浓缩和核碎片。细胞死亡分析表明，与对照组相比，治疗小鼠的肝细胞凋亡明显。还发现 TCE 会诱导氧化应激，如氧化应激标志物脂质过氧化水平的增加所表明。与对照组相比，治疗组肝细胞的 DNA 含量也显着降低。琼脂糖凝胶电泳还通过显示肝细胞中的核小体间 DNA 断裂提供了细胞凋亡的进一步生化证据，表明氧化应激是 DNA 损伤的原因。这些结果表明，任何新化学品在进入消费市场之前都需要进行完整的风险评估。
Exposures to a wide variety of environmental substances are negatively associated with many biological cell systems both in humans and rodents. Trichloroethane (TCE), a ubiquitous environmental toxicant, is used in large quantities as a dissolvent, metal degreaser, chemical intermediate, and component of consumer products. This increases the likelihood of human exposure to these compounds through dermal, inhalation and oral routes. The present in vivo study was aimed to investigate the possible cellular and molecular etiology of liver abnormality induced by early exposure to TCE using a murine model. The results showed a significant increase in liver weight. Histopathological examination revealed a TCE-induced hepatotoxicity which appeared as heavily congested central vein and blood sinusoids as well as leukocytic infiltration. Mitotic figures and apoptotic changes such as chromatin condensation and nuclear fragments were also identified. Cell death analysis demonstrates hepatocellular apoptosis was evident in the treated mice compared to control. TCE was also found to induce oxidative stress as indicated by an increase in the levels of lipid peroxidation, an oxidative stress marker. There was also a significant decrease in the DNA content of the hepatocytes of the treated groups compared to control. Agarose gel electrophoresis also provided further biochemical evidence of apoptosis by showing internucleosomal DNA fragmentation in the liver cells, indicating oxidative stress as the cause of DNA damage. These results suggest the need for a complete risk assessment of any new chemical prior to its arrival into the consumer market.