A single pretreatment with clofibric acid attenuates carbon tetrachloride-induced necrosis, but not steatosis, in rat liver

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.