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

Abstract

Environmental heat stress is a multifaceted physiological challenge that results in hepatic lipid peroxidation and oxidative DNA damage in old rats. Since iron can catalyze oxidative reactions, it may contribute to the cellular damage observed after heat stress. To delineate the role of iron in this model, young (6 mo) and old (24 mo) Fischer 344 rats were subjected to either a sham-heating protocol or a two-heat stress protocol. Livers were harvested at several time points after the second heating and assayed for storage iron (assessed via a non-heme iron assay) and free iron (via electron paramagnetic resonance spectroscopy). In the non-stressed condition, storage iron was significantly higher in old rats, but there were no differences in free iron between age groups. Both storage and free iron were not altered by heat stress in young rats, but both were increased in old rats after heating. These results suggest that aging enhances iron flux after heat stress. To investigate whether increased hepatic iron content exacerbates oxidative damage after heating, young rats were iron-loaded and then subjected to heat stress. Iron loading raised iron content to levels observed in old rats, but did not alter lipid peroxidation damage after heat stress. These differences in iron regulation suggest that it may play an important role in catalyzing hepatic oxidative damage in old rats after heat stress. Supported by NIH AG12350.