title: Roles of lipoxin A4 in preventing paracetamol-induced acute hepatic injury in a rabbit model.
abstract: The objective of this research is to investigate the potential role of lipoxin A4 in preventing paracetamol (PCM)-induced hepatic injury. One hundred male New Zealand white rabbits were randomly divided into control group, PCM group, N-acetylcysteine (NAC) group, lipoxin A4 (LXA4) group, and LXA4 + NAC group. The rabbits were assigned to receive 300 mg/kg weight PCM in 0.9 % saline or equivalent volume of saline via gastric lavage. LXA4 (1.5 μg/kg) and equivalent volume of 2 % ethanol were separately given to the rabbits in LXA4-treated and PCM groups 24 h after PCM administration. Meanwhile, the rabbits in the NAC-treated groups received a loading dose of 140 mg/kg of N-acetylcysteine. The blood samples and liver tissue were collected for biochemical and histological evaluation 36 h after paracetamol administration. The administration of LXA4 24 h after paracetamol poisoning resulted in significant improvement in hepatic injury as represented by decrease of hepatocellular enzyme release and attenuation of hepatocyte apoptosis and necrosis. In LXA4-treated groups, the expression of TNF-α was significantly lower than those in PCM and NAC groups (p < 0.05). In contrast, the level of IL-10 was significantly higher than PCM and NAC groups (p < 0.05). Moreover, the expressions of NF-κB p65 in PCM and NAC groups were significantly increased compared with those of LXA4-treated groups and control group (respectively, p < 0.05 and p < 0.01). LXA4-treated groups also showed significantly higher survival rates. Lipoxin A4 significantly mitigates paracetamol-induced hepatic injury, in which anti-inflammation effect may play an important role, leading to hepatic apoptosis and necrosis.
authors.affiliation: Emergency Center, Zhongnan Hospital, Wuhan University, 169 Donghu Road, Wuchang, Wuhan, Hubei, 430071, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Xia
authors.forename: Xian-Long
authors.initials: XL
authors.lastname: Zhou
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.forename: You-Qing
authors.initials: YQ
authors.lastname: Zhu
authors.forename: Shan
authors.initials: S
authors.lastname: Jiang
authors.forename: Shao-Zhou
authors.initials: SZ
authors.lastname: Ni
mesh_terms: D000082:Acetaminophen; D000111:Acetylcysteine / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000517:prevention & control; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy; D016753:Interleukin-10 / Q000096:biosynthesis; D044045:Lipoxins / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D011817:Rabbits; D051996:Transcription Factor RelA / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D044045:Lipoxins; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C040527:lipoxin A4; D016753:Interleukin-10; D000082:Acetaminophen; D000111:Acetylcysteine