Ciliary neurotrophic factor analogue aggravates CCl₄-induced acute hepatic injury in rats

Ciliary neurotrophic factor (CNTF) and CNTF analogs were reported to have hepatoprotective effect and ameliorate hepatic steatosis in db/db or high-fat-diet-fed mice. Because hepatic steatosis and injury are also commonly induced by hepatotoxin, the aim of the present study is to clarify whether CNTF could alleviate hepatic steatosis and injury induced by carbon tetrachloride (CCl₄). Unexpectedly, when combined with CCl₄, CNTF aggravated hepatic steatosis and liver injury. The mechanism is associated with effects of CNTF that inhibited lipoprotein secretion and drastically impaired the ability of lipoproteins to act as transport vehicles for lipids from the liver to the circulation. While injected after CCl₄ cessation, CNTF could improve liver function. These data suggest that CNTF could be a potential hepatoprotective agent against CCl₄-induced hepatic injury after the cessation of CCl₄ exposure. However, it is forbidden to combine recombinant mutant of human CNTF treatment with CCl₄.