Heat-induced liver injury in old rats is associated with exaggerated oxidative stress and altered transcription factor activation

SPECIFIC AIMSLittle is known about the potential effect of aging on stress-induced oxidative damage in vivo and the extent of any subsequent physiological injury. Thus, we examined the effects of heat stress on steady-state levels of ROS, oxidative injury, changes in redox status, and DNA binding activation of critical stress response transcription factors (AP-1 and NF-κB) in old vs. young rats. Experiments focused on the liver because it shows age-dependent evidence of increased ROS levels and is a prime target of tissue injury from environmental challenge. We hypothesized that older animals would have exaggerated oxidative stress and aberrant activation of stress response transcription factors in response to heat stress, leading to cellular dysfunction and age-related reductions in stress tolerance.PRINCIPAL FINDINGS1. Heat stress results in substantial hepatic injury in old ratsTo determine the extent of liver injury from a physiologically relevant level of heat stress, young and old Fischer 344 rats w...