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This Article Full Text Full Text (PDF) All Versions of this Article: 294/4/R1165    most recent 00719.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Bloomer, S. A. Articles by Kregel, K. C. PubMed PubMed Citation Articles by Bloomer, S. A. Articles by Kregel, K. C.

APPETITE, OBESITY, DIGESTION, AND METABOLISM

Dysregulation of hepatic iron with aging: implications for heat stress-induced oxidative liver injury

¹Department of Integrative Physiology, ²Iowa City Veterans Administration Medical Center, Iowa City, Iowa; ³Division of Gastroenterology-Hepatology, Roy J. and Lucille A. Carver College of Medicine, and ⁴Program in Free Radical and Radiation Biology, Department of Radiation Oncology, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, Iowa

Submitted 4 October 2007 ; accepted in final form 8 February 2008

Environmental heat stress is associated with an age-related increase in hepatic oxidative damage and an exaggerated state of oxidative stress. The purpose of this investigation was to evaluate the regulation of hepatic iron after heat stress. A secondary aim was to determine a potential role for iron in heat stress-induced liver injury. Hyperthermia-induced alterations in hepatic iron were evaluated in young (6 mo) and old (24 mo) Fischer 344 rats by exposing them to a two-heat stress protocol. Livers were harvested at several time points after the second heating and assayed for labile and nonheme iron. In the control condition, there was no difference in labile iron between age groups. Both labile iron and storage iron were not altered by hyperthermia in young rats, but both were increased immediately after heating in old rats. To evaluate a role for iron in liver injury, hepatic iron content was manipulated in young and old rats, and then both groups were exposed to heat stress. Iron administration to young rats significantly increased hepatic iron content and ferritin but did not affect markers of lipid peroxidation under control conditions or after heat stress. In old rats, iron chelation with deferoxamine prevented the increase in nonheme iron, labile iron, ferritin, and lipid peroxidation after heat stress. These results suggest that iron may play a role in hepatic injury after hyperthermia. Thus, dysregulation of iron may contribute to the gradual decline in cellular and physiological function that occurs with aging.

reactive oxygen species; deferoxamine; hyperthermia; electron paramagnetic resonance spectroscopy; inflammation