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Redox modulation of the liver with chronic antioxidant enzyme mimetic treatment prevents age‐related oxidative damage associated with environmental stress
Author(s) -
Zhang Hannah J.,
Doctrow Susan R.,
Xu Linjing,
Oberley Larry W.,
Beecher Benjamin,
Morrison Joanna,
Oberley Terry D.,
Kregel Kevin C.
Publication year - 2004
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/fj.04-1629fje
Subject(s) - oxidative stress , catalase , superoxide dismutase , lipid peroxidation , antioxidant , reactive oxygen species , oxidative phosphorylation , chemistry , liver injury , pharmacology , biochemistry , medicine , endocrinology
A reduction in stress tolerance is a hallmark of the aging process, and the lowered functional capacity observed in aged organisms is associated with an increased rate of oxidative stress and a greater susceptibility of aged tissues to oxidative injury. In this report, we show that chronic systemic administration of a superoxide dismutase (SOD)/catalase mimetic (EUK‐189), delivered over a 1 month period via osmotic pump, prevents heat stress‐induced liver injury by dramatically decreasing oxidative damage in aged animals. Widespread liver injury was present in old but not young vehicle‐treated rats in response to a 2 day heating protocol. However, SOD/catalase mimetic treatment markedly decreased the hyperthermia‐induced liver injury associated in old animals. The reversal of damage with EUK‐189 was associated with an improvement in intracellular redox status and a striking reduction in hepatocellular lipid peroxidation. EUK‐189 treatment also blocked the activation of activator protein‐1 (AP‐1), which is a redox‐sensitive early response transcription factor involved in the regulation of cellular stress responses. These results demonstrate that oxidative stress plays a unique role in age‐related hyperthermic injury and suggest that therapeutic strategies aimed at improving redox potential, such as chronic SOD/catalase mimetic treatment, can prevent the oxidative‐mediated damage associated with environmental stress.