title: Prevention of liver ischemia reperfusion injury by a combined thyroid hormone and fish oil protocol.
abstract: Several preconditioning strategies are used to prevent ischemia-reperfusion (IR) liver injury, a deleterious condition associated with tissue resection, transplantation or trauma. Although thyroid hormone (T₃) administration exerts significant protection against liver IR injury in the rat, its clinical application is controversial due to possible adverse effects. Considering that prevention of liver IR injury has also been achieved by n-3 polyunsaturated fatty acid (n-3 PUFA) supplementation to rats, we studied the effect of n-3 PUFA dietary supplementation plus a lower dose of T₃ against IR injury. Male Sprague-Dawley rats receiving fish oil (300 mg/kg) for 3 days followed by a single intraperitoneal dose of 0.05 mg T₃/kg were subjected to 1 h of ischemia followed by 20 h of reperfusion. Parameters of liver injury (serum transaminases, histology) and oxidative stress (liver contents of GSH and oxidized proteins) were correlated with fatty acid composition, NF-κB activity, and tumor necrosis factor-α (TNF-α) and haptoglobin expression. IR significantly modified liver histology; enhanced serum transaminases, TNF-α response or liver oxidative stress; and decreased liver NF-κB activity and haptoglobin expression. Although IR injury was not prevented by either n-3 PUFA supplementation or T₃ administration, substantial decrease in liver injury and oxidative stress was achieved by the combined protocol, which also led to increased liver n-3 PUFA content and decreased n-6/n-3 PUFA ratios, with recovery of NF-κB activity and TNF-α and haptoglobin expression. Prevention of liver IR injury achieved by a combined protocol of T₃ and n-3 PUFA supplementation may represent a novel noninvasive preconditioning strategy with potential clinical application.
authors.affiliation: Oxidative Stress and Hepatotoxicity Laboratory, Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Santiago 7, Chile.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Mardones
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Valenzuela
authors.forename: Pamela
authors.initials: P
authors.lastname: Romanque
authors.forename: Natalia
authors.initials: N
authors.lastname: Covarrubias
authors.forename: Fiorella
authors.initials: F
authors.lastname: Anghileri
authors.forename: Virginia
authors.initials: V
authors.lastname: Fernández
authors.forename: Luis A
authors.initials: LA
authors.lastname: Videla
authors.forename: Gladys
authors.initials: G
authors.lastname: Tapia
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use; D000975:Antioxidants / Q000008:administration & dosage / Q000032:analysis / Q000627:therapeutic use*; D019587:Dietary Supplements; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use; D005395:Fish Oils / Q000627:therapeutic use*; D018565:Food-Drug Interactions; D005786:Gene Expression Regulation / Q000187:drug effects; D006242:Haptoglobins / Q000235:genetics / Q000378:metabolism; D048550:Hepatic Insufficiency / Q000209:etiology / Q000517:prevention & control; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D014284:Triiodothyronine / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D006242:Haptoglobins; C529146:Hp protein, rat; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D014284:Triiodothyronine