title: Hypertonic preconditioning prevents hepatocellular injury following ischemia/reperfusion in mice: a role for interleukin 10.
abstract: Ischemia/reperfusion (I/R) of the liver occurs in many clinical scenarios including trauma, elective surgery, and transplantation. Events initiated by this process can lead to inflammation in the liver, culminating in local injury as well as distant organ dysfunction. Recent studies have suggested that hypertonic saline exerts anti-inflammatory effects, which may be beneficial in preventing organ injury. In the present study, we examine the effect of hypertonic saline on the development of liver inflammation following I/R in both rat and mouse models. Hypertonic pretreatment was shown to prevent liver enzyme release concomitant with a reduction in liver neutrophil sequestration. Hypertonic saline appeared to exert this effect by inhibiting liver tumor necrosis factor alpha (TNF-alpha) generation, an effect that culminated in reduced liver adhesion molecule expression. Hypertonic saline pretreatment was shown to augment liver interleukin 10 (IL-10) expression following I/R, as a potential mechanism underlying its anti-inflammatory effect. To examine the role of IL-10 in the protective effect of hypertonic saline on liver I/R injury, we used a murine model of I/R. In wild type mice, hypertonic pretreatment similarly prevented liver injury induced by I/R. However, in IL-10 knockout animals, hypertonic pretreatment was unable to prevent the liver enzyme release, TNF-alpha generation, or neutrophil sequestration induced by I/R. In conclusion, these findings define a novel mechanism responsible for the anti-inflammatory effects of hypertonic saline and also suggest a potential clinical role for hyperosmolar solutions in the prevention of liver injury associated with I/R.
authors.affiliation: Department of Surgery, University Health Network and University of Toronto, Toronto, Ontario, Canada.
authors.forename: George D
authors.initials: GD
authors.lastname: Oreopoulos
authors.forename: Heshui
authors.initials: H
authors.lastname: Wu
authors.forename: Kati
authors.initials: K
authors.lastname: Szaszi
authors.forename: Jie
authors.initials: J
authors.lastname: Fan
authors.forename: John C
authors.initials: JC
authors.lastname: Marshall
authors.forename: Rachel G
authors.initials: RG
authors.lastname: Khadaroo
authors.forename: Ruijan
authors.initials: R
authors.lastname: He
authors.forename: Andras
authors.initials: A
authors.lastname: Kapus
authors.forename: Ori D
authors.initials: OD
authors.lastname: Rotstein
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects; D016753:Interleukin-10 / Q000378:metabolism*; D008099:Liver / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008102:Liver Circulation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D012462:Saline Solution, Hypertonic / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D012462:Saline Solution, Hypertonic; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D001219:Aspartate Aminotransferases