title: Pseudoephedrine/ephedrine shows potent anti-inflammatory activity against TNF-α-mediated acute liver failure induced by lipopolysaccharide/D-galactosamine.
abstract: The anti-inflammatory effects of pseudoephedrine/ephedrine were investigated using the experimental model of lipopolysaccharide (LPS)-induced acute liver failure in D-galactosamine (D-GalN)-sensitised male rats in order to elucidate effects other than sympathomimetic effects. Rats were intraperitoneally injected with D-GalN (400 mg/kg) and LPS (40 μg/kg) to induce acute liver failure. The treatment groups were then intraperitoneally administered pseudoephedrine/ephedrine at 0 h and 4 h after induction and the activation induced by treatment with pseudoephedrine and/or LPS on the primary Kupffer cells (KCs) was monitored. Compared with controls induced by GalN/LPS alone, pseudoephedrine dramatically reduced the infiltration of inflammatory cells and bile ductular hyperplasia and hepatic necrosis observed in liver sections. It inhibited both hepatocellular apoptosis and the expression of monocyte chemotactic protein-1. It lowered the production of tumour necrosis factor-α (TNF-α) in the beginning of acute liver failure induced by D-GalN/LPS. Correspondingly, levels of alanine aminotransferase (ALT), total bilirubin (TBIL) and malondialdehyde were attenuated. Ephedrine demonstrated all these identical protective effects as well. In addition, pseudoephedrine significantly suppressed the production of p-IκB-α, reducing the degradation of sequestered nuclear factor kappa B (NF-κB) in the cytoplasm, and inhibited the translocation of NF-κB/p65 to the nucleus, the transcription of TNF-α mRNA and the production of TNF-α in primary KCs. These results suggest that pseudoephedrine and ephedrine have a potent anti-inflammatory activity against D-GalN/LPS-induced acute liver failure in rats, and this comprehensive anti-inflammatory effect may result from the inhibition of TNF-α production.
authors.affiliation: Teaching & Research Department of Clinical and Classic Medicine, College of Basic Medical Science, Shanghai University of Traditional Chinese Medicine, 1200 Cai lun Road, Shanghai 201203, China. Electronic address: wzp@shutcm.edu.cn.
authors.forename: Zhongping
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Teaching & Research Department of Clinical and Classic Medicine, College of Basic Medical Science, Shanghai University of Traditional Chinese Medicine, 1200 Cai lun Road, Shanghai 201203, China.
authors.forename: Xiangliang
authors.initials: X
authors.lastname: Kong
authors.affiliation: Teaching & Research Department of Clinical and Classic Medicine, College of Basic Medical Science, Shanghai University of Traditional Chinese Medicine, 1200 Cai lun Road, Shanghai 201203, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Teaching & Research Department of Clinical and Classic Medicine, College of Basic Medical Science, Shanghai University of Traditional Chinese Medicine, 1200 Cai lun Road, Shanghai 201203, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Ye
authors.affiliation: Teaching & Research Department of Clinical and Classic Medicine, College of Basic Medical Science, Shanghai University of Traditional Chinese Medicine, 1200 Cai lun Road, Shanghai 201203, China.
authors.forename: Zhaoqin
authors.initials: Z
authors.lastname: Fang
authors.affiliation: Department of Nephrology, Shuguang Hospital Affiliated with Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai 201203, China. Electronic address: qqyang@hotmail.com.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Yang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000276:immunology; D004809:Ephedrine / Q000494:pharmacology / Q000627:therapeutic use*; D007728:Kupffer Cells / Q000187:drug effects / Q000502:physiology; D008070:Lipopolysaccharides; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000276:immunology; D054199:Pseudoephedrine / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D054199:Pseudoephedrine; D004809:Ephedrine
keywords: Acute liver failure; Anti-inflammatory activity; Ephedrine; Hepatotoxicity; Kupffer cell; Pseudoephedrine