2020年11月
A single pretreatment with clofibric acid attenuates carbon tetrachloride-induced necrosis, but not steatosis, in rat liver.
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
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- 巻
- 145
- 号
- 開始ページ
- 111591
- 終了ページ
- 111591
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1016/j.fct.2020.111591
The present study investigated whether a single pretreatment with clofibric acid suppresses liver injury in rats after CCl4 intoxication. Rats received a single pretreatment with clofibric acid (100 mg/kg, i.p.) 1 h prior to a CCl4 (1 mL/kg, p.o.) challenge, and were euthanized 24 h after the CCl4 administration. A single pretreatment with clofibric acid effectively suppressed increases in the serum aminotransferase activities and the severity of necrosis following the CCl4 challenge, whereas the pretreatment did not protect against CCl4-induced fatty liver. The clofibric acid pretreatment did not affect blood concentrations of CCl4 in the early stage after CCl4 dosing, or the level of the CCl4 reaching the liver 1 h after the CCl4 challenge. Moreover, the clofibric acid pretreatment did not affect the intensity of the covalent binding of the [14C]CCl4 metabolite to microsomal proteins and lipids. The clofibric acid pretreatment did not alter microsomal cytochrome P450 2E1 activity. Based on these results, we conclude that protection against CCl4-induced hepatocellular necrosis by a clofibric acid pretreatment does not require its repeated administration, and that a single and brief pre-exposure to clofibric acid prior to CCl4 dosing markedly suppresses necrosis without affecting the development and progression of steatosis.
- リンク情報
- ID情報
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- DOI : 10.1016/j.fct.2020.111591
- PubMed ID : 32739454