Protection against in vivo liver ischemia-reperfusion injury by n-3 long-chain polyunsaturated fatty acids in the rat.
N-3 polyunsaturated fatty acids (n-3 PUFA) affect inflammatory processes. This study evaluated the effects of dietary supplementation with fish oil on hepatic ischemia-reperfusion (IR) injury in the rat. Parameters of liver injury (serum transaminases and histology) and oxidative stress (serum 8-isoprostanes and hepatic GSH and GSSG), were correlated with NF-kappaB DNA binding and FA composition and inflammatory cytokine release. N-3 PUFA supplementation significantly increased liver n-3 PUFA content and decreased n-6/n-3 PUFA ratios. IR significantly modified liver histology and enhanced serum transaminases, 8-isoprotanes and inflammatory cytokines, with net reduction in liver GSH levels and net increment in those of GSSG. Early increase (3 h) and late reduction (20 h) in NF-kappaB activity was induced. All IR-induced changes were normalized by n-3 PUFA supplementation. In conclusion, prevention of liver IR-injury was achieved by n-3 PUFA supplementation, with suppression of oxidative stress and recovery of pro-inflammatory cytokine homeostasis and NF-kappaB functionality lost during IR.
Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, University of Chile, Santiago-7, Chile.
Jessica
J
Zúñiga
Francisca
F
Venegas
Marcela
M
Villarreal
Daniel
D
Núñez
Marlene
M
Chandía
Rodrigo
R
Valenzuela
Gladys
G
Tapia
Patricia
P
Varela
Luis A
LA
Videla
Virginia
V
Fernández
D000818:Animals; D016207:Cytokines / Q000097:blood / Q000276:immunology; D004247:DNA / Q000187:drug effects; D019587:Dietary Supplements; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000276:immunology / Q000517:prevention & control*
D016207:Cytokines; D015525:Fatty Acids, Omega-3; D016328:NF-kappa B; D004247:DNA