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MECHANISM OF CARBON TETRACHLORIDE HEPATOTOXICITY

四氯化碳肝毒性机制

基本信息

批准号：
3150850
负责人：
JOSE A CASTRO
金额：
$ 6.62万
依托单位：
NAVAL INSTITUTE OF SCI & TECH RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
1979
资助国家：
美国
起止时间：
1979-01-01 至 1988-06-30
项目状态：
已结题

项目摘要

We plan to continue with our studies on the relative importance of the covalent binding of carbon tetrachloride reactive metabolites and lipid peroxidation in carbon tetrachloride-induced liver injury. We also plan to continue with studies directed to understand how cellular alterations initiated by carbon tetrachloride at the cytochrome P-450 site in the endoplasmic reticulum propagate to other cell organelles like the Golgi apparatus, plasma membrane, and the cytoplasm. We plan to perform studies directed to understand the mechanism by which disruption of calcium homeostasis during carbon tetrachloride poisoning initiates the chain of events ending in liver cell necrosis. We plan to further explore the possible role of processes of synthesis and degradation of cellular constituents in carbon tetrachloride-induced liver necrosis. Particular emphasis in protein and phospholipid degradation is going to be made. A major area of research effort in our project, is going to be the development of treatment/antidotes preventing liver cell necrosis, based on our studies on the mechanism of carbon tetrachloride-induced liver injury. We plan to explore the possibility that insights gained from the studies on cell injury by the model hepatotoxin carbon tetrachloride allowed prevention of liver cell necrosis by other hepatotoxins and cell necrosis produced by other chemicals acting in other organs like pancreas, small intestine, kidney or testes. Health implications of this project are critical, since the aim of our research is to understand how cells die after chemical or other insult and how that understanding can be used to develop treatments.

我们计划继续研究四氯化碳反应性代谢产物与脂质的共价结合四氯化碳所致肝损伤中的过氧化反应。我们还计划继续进行研究，以了解细胞如何四氯化碳引起的细胞色素P-450位点的改变在内质网中传播到其他细胞器，如高尔基体、质膜和细胞质。我们计划进行研究，以了解四氯化碳中毒时钙稳态的破坏引发一连串的事件，最终导致肝细胞坏死。我们计划进一步探索合成和合成过程中可能发挥的作用四氯化碳诱导的肝脏细胞成分的降解坏死。特别强调蛋白质和磷脂的降解会被制造出来的。我们项目中的一个主要研究领域将是预防肝细胞坏死的治疗/解毒剂的研究进展我们对四氯化碳致肝损伤机制的研究。我们计划探讨从研究中获得的见解是否有可能四氯化碳所致模型肝毒素对细胞的损伤其他肝毒素预防肝细胞坏死及细胞坏死的研究由作用于胰腺等其他器官的其他化学物质产生的，小的肠道、肾脏或睾丸。这个项目对健康的影响至关重要，因为我们的目标是研究是为了了解细胞在化学或其他侮辱后是如何死亡的如何利用这种理解来开发治疗方法。