title: Chronic lithium treatment protects against liver ischemia/reperfusion injury in rats.
abstract: Lithium has long been widely used in the treatment of bipolar mood disorders. Recent studies have demonstrated that lithium is able to decrease ischemia/reperfusion (I/R) injury in the brain, kidneys, and heart. Because lithium may act on a number of stress and survival pathways, it is of great interest to explore this compound also in the setting of liver I/R injury. In this study, we aimed to evaluate the effects of lithium in a model of liver I/R injury in rats. Chronic treatment with lithium (2 mmol/kg for 3 days before ischemia) decreased I/R injury, whereas acute treatment with a single dose of lithium (2 mmol/kg 1 hour before ischemia) did not confer any protection in a partial hepatic I/R model. Furthermore, rats subjected to chronic lithium treatment had a significantly better survival rate (60%) than saline-treated rats (27%) in a total hepatic I/R survival model. Chronic lithium treatment protected against liver I/R injury, as indicated by lower serum aminotransferase levels, fewer I/R-associated histopathological changes, lower hepatic inflammatory cytokine levels, less neutrophil infiltration, and lower hepatic high-mobility group box expression and serum levels. The mechanism of action of lithium appears to involve its ability to inhibit glycogen synthase kinase 3β activation, modulate mitogen-activated protein kinase activation, inhibit hepatic apoptosis, and induce autophagy. On the basis of these data, we conclude that lithium treatment may be a simple and applicable preconditioning intervention for protecting against liver I/R injury.
authors.affiliation: Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Anding
authors.initials: A
authors.lastname: Liu
authors.forename: Haoshu
authors.initials: H
authors.lastname: Fang
authors.forename: Uta
authors.initials: U
authors.lastname: Dahmen
authors.forename: Olaf
authors.initials: O
authors.lastname: Dirsch
mesh_terms: D000818:Animals; D017209:Apoptosis; D016207:Cytokines / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D024002:HMGB Proteins / Q000378:metabolism; D007249:Inflammation / Q000473:pathology; D018021:Lithium Chloride / Q000008:administration & dosage*; D008099:Liver / Q000473:pathology*; D008107:Liver Diseases / Q000188:drug therapy / Q000517:prevention & control*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology*; D015398:Signal Transduction; D013997:Time Factors; D000637:Transaminases / Q000097:blood
chemical_list: D016207:Cytokines; D024002:HMGB Proteins; D000637:Transaminases; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D020928:Mitogen-Activated Protein Kinases; D038362:Glycogen Synthase Kinase 3; D018021:Lithium Chloride