title: Magnesium lithospermate B reduces inflammatory response in a mouse model of hepatic ischemia-reperfusion injury.
abstract: It has been well proved that acute inflammatory response and hepatocellular apoptosis contributed to the pathogenesis of liver ischemia reperfusion (IR) injury. A vast amount of research has demonstrated that magnesium lithospermate B (MLB) has potent anti-apoptosis and potential anti-inflammatory pharmacological properties. However, it has not previously been examined whether MLB can attenuate hepatic IR injury. Firstly, the optimal dose of MLB to protect against hepatic IR injury was determined using hepatic IR model in mice. Then, the effect of MLB on IR-induced inflammatory response was detected in detail. We found that MLB exhibited protective effect from the beginning of 50 mg/kg and culminated at the doses of 100 and 200 mg/kg. The alanine aminotransferase and aspartate aminotransferase levels in MLB group were markedly decreased. Severe hepatocellular swelling/necrosis, sinusoidal/vascular congestion and inflammatory cell infiltration were seen and a large number of apoptotic cells were found in the liver samples from Saline group, while minimal damage and very few apoptotic cells were noted in the samples from MLB group. Kuppfer cells infiltration, myeloperoxidase activity and mRNA level of CD11b in MLB group was significantly decreased. Serum TNF-a and IL-6, and mRNA expression of CXCL-10 and ICAM-1 was markedly decreased in the samples from MLB group. Inflammatory signaling pathway activation was largely prevented in MLB group. MLB can significantly attenuate IR-induced hepatocellular damage and hepatocellular apoptosis by preventing inflammatory signaling pathways activation, inflammatory mediators expression and macrophage and neutrophil infiltration.
authors.affiliation: Department of Organ Transplantation, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Huangpu District, Shanghai, 200003, China.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Song
authors.forename: Wenyu
authors.initials: W
authors.lastname: Liu
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.forename: Zhengxin
authors.initials: Z
authors.lastname: Wang
authors.forename: Guoshan
authors.initials: G
authors.lastname: Ding
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Guo
authors.forename: Zhiren
authors.initials: Z
authors.lastname: Fu
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001219:Aspartate Aminotransferases / Q000378:metabolism; D039481:CD11b Antigen / Q000235:genetics / Q000378:metabolism; D054357:Chemokine CXCL10 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D009195:Peroxidase / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D039481:CD11b Antigen; D054357:Chemokine CXCL10; D004365:Drugs, Chinese Herbal; C090509:Icam1 protein, mouse; D018836:Inflammation Mediators; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C061091:lithospermate B; D018799:Intercellular Adhesion Molecule-1; D009195:Peroxidase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase