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 CCl4cessation, 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 CCl4exposure. However, it is forbidden to combine recombinant mutant of human CNTF treatment with CCl4.
a Institute of Pharmacology, School of Basic Medical Science, Lanzhou University; Key Laboratory of Preclinical Study for New Drug of Gansu Province, Lanzhou 730000, China.
Ming-Xia
MX
Cui
b Gansu Provincial Cancer Hospital, Lanzhou 730050, China.
Jun-Feng
JF
Jiang
c The First Hospital of Lanzhou University, Lanzhou 730000, China.
Guang-Ning
GN
Min
d Dingxi District of Gansu University of Chinese Medicine, Dingxi 743000, China.
Wei
W
Han
a Institute of Pharmacology, School of Basic Medical Science, Lanzhou University; Key Laboratory of Preclinical Study for New Drug of Gansu Province, Lanzhou 730000, China.
Yong-Jie
YJ
Wu
D000818:Animals; D002251:Carbon Tetrachloride / Q000494:pharmacology*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D020934:Ciliary Neurotrophic Factor / Q000009:adverse effects* / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D008074:Lipoproteins / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012449:Safety
D020934:Ciliary Neurotrophic Factor; D008074:Lipoproteins; D002251:Carbon Tetrachloride
carbon tetrachloride (CCl4); ciliary neurotrophic factor (CNTF); facteur neurotrophique ciliaire (CNTF); fatty liver; lipid peroxidation; liver injury; lésions hépatiques; peroxydation lipidique; stéatose hépatique; tétrachlorure de carbone (CCl4)