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Treatment with thioredoxin decreases liver injury after short‐term ethanol exposure in mice
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.445.7
Subject(s) - steatosis , cyp2e1 , chemistry , oxidative stress , liver injury , reactive oxygen species , medicine , endocrinology , intraperitoneal injection , glutathione , antioxidant , thioredoxin , cytokine , proinflammatory cytokine , inflammation , pharmacology , biochemistry , metabolism , enzyme , cytochrome p450
Ethanol (EtOH)‐induced liver injury is characterized by increased formation of reactive oxygen species (ROS) and inflammatory cytokines, resulting in the development of hepatic steatosis and injury. Thioredoxin (Trx), a potent antioxidant and anti‐inflammatory molecule, decreases production of ROS and inflammatory cytokines in other chronic inflammatory diseases. We tested the hypothesis that Trx can prevent EtOH‐induced liver damage because of its anti‐inflammatory and antioxidant properties. C57BL/6 mice were allowed ad libitum access to a Lieber‐deCarli EtOH containing diet (5.4% (% of kcal) for 2 days, 32.4% for 2 days) or pair‐fed control diet. During this time, mice received a daily intraperitoneal injection of either 5 g/kg of Trx or saline. EtOH feeding increased expression of hepatic TNFα and IFNγ, accumulation of 4‐hydroxynonenal (4‐HNE) adducts, and resulted in hepatic steatosis and increased plasma ALT and AST. In EtOH‐fed mice, Trx reduced inflammatory cytokine production and 4‐HNE adduct accumulation, decreased hepatic triglyceride and improved liver enzyme profiles. CYP2E1 was induced after EtOH feeding, but Trx did not prevent this induction. These data suggest that Trx protects against EtOH‐induced liver injury in mice by decreasing oxidative and inflammatory damage.