title: Effects of anti-histamine treatment on liver injury triggered by small intestinal ischemia reperfusion in rats.
abstract: Mast cell (MC) degranulation has been implicated in small intestinal ischemia reperfusion (IIR) injury, therein, inhibiting overproduction of histamine released from activated MC may provide promising strategies against IIR-mediated liver injuries. The aim of the present study was to explore whether anti-histamine treatment contribute to attenuating IIR-mediated liver injury. Adult SD rats were randomized into sham-operated group (S group), sole IIR group (IIR group), and IIR treated with Ketotifen, a histamine antagonist (IIR+K group), Cromolyn Sodium, a MC stabilizer (IIR+C group), and Compound 48/80, a MC degranulator (IIR+CP group), respectively. IIR was induced by superior mesenteric artery occlusion for 75 min followed by 4 h of reperfusion. The agents were intravenously administrated 5 min before reperfusion to induce different levels of histamine. Subsequently, serum concentrations of ALT, AST and histamine; levels of LDH,TNF-α, IL-8 and MDA as well as SOD activities in the liver were assessed. Histopathologic changes were also evaluated. IIR resulted in severe liver injury as demonstrated by significant increases in injury scores, with concomitant significant increases in serum ALT, AST and histamine levels, as well as LDH, TNF-α, IL-8, and MDA levels in the liver, accompanied by reduction in SOD activities (all P < 0.05, IIR vs. S). Treatments by Ketotifen and Cromolyn Sodium similarly markedly alleviated IIR-mediated liver injury as confirmed by significant reduction of the above biomedical changes whereas Compound 48/80 further aggravated IIR-mediated liver injury by dramatically enhancing the above biomedical changes. Data of our study suggest that anti-histamine treatments may provide promising benefits in alleviating liver injury triggered by IIR.
authors.affiliation: Department of Anesthesiology, Guangzhou 510630, Guangdong, People's Republic of China.
authors.forename: Pin-Jie
authors.initials: PJ
authors.lastname: Huang
authors.forename: Xiao-Liang
authors.initials: XL
authors.lastname: Gan
authors.forename: Jian-Pei
authors.initials: JP
authors.lastname: Liu
authors.forename: De-Zhao
authors.initials: DZ
authors.lastname: Liu
authors.forename: Yan-Ling
authors.initials: YL
authors.lastname: Wang
authors.forename: Zi-Qing
authors.initials: ZQ
authors.lastname: Hei
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D015550:Cell Degranulation / Q000187:drug effects; D006632:Histamine / Q000097:blood; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D016209:Interleukin-8 / Q000378:metabolism; D007421:Intestine, Small / Q000187:drug effects*; D007665:Ketotifen / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008107:Liver Diseases / Q000188:drug therapy* / Q000201:enzymology; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000201:enzymology; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
chemical_list: D006634:Histamine H1 Antagonists; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D003189:p-Methoxy-N-methylphenethylamine; D006632:Histamine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D007665:Ketotifen