Chronic Acetaminophen Alters Age-Associated Changes in Oxidative Stress Signaling in F344XBN Rat Inferior Vena Cava

Abstract

Background: Age associated cardiovascular disease is thought to be caused in part by the gradual oxidative damage to biomolecules. We have previously reported that aging in the Fisher344 X Brown Norway (FBN) rat aorta is characterized by increased levels of ROS and alterations in oxidative stress induced cell signaling. Acetaminophen was found to scavenge free radicals in recent ischemia-reperfusion studies. It remains unknown if chronic acetaminophen administration influences ROS signaling in the aging inferior vena cava (IVC). PURPOSE: Here we examined if chronic treatment with a therapeutic dose of acetaminophen attenuates age-associated alterations in ROS-related signaling in the IVC. METHODS: FBN rats (27 month; n=8) were subjected to 6 months of treatment with a therapeutic dose of acetaminophen (30mg/kg/day), with age-matched untreated FBN rats as controls. Immunoblotting analysis was used to examine the expression and activation of signaling molecules, which were previously shown to be affected by oxidative stress in the IVC. RESULTS: Immunoblotting analysis revealed that when compared to IVC from 6 month control animals, the total levels of NFκB p65 in 33 month-old control and treated IVC were 50.43±11.41% and 26.52±7.94% lower, respectively. Corresponding phospho-Erk1/2 levels were 21.51±7.66%, 94.97±17.16% higher and phospho-AMPK levels were 148.94±17.72% and 88.53±27.40% higher, respectively. CONCLUSION: Chronic acetaminophen treatment altered the age associated expression of ROS related signaling molecules in FBN rat IVC, suggesting that acetaminophen may have a protective effect against oxidative stress. (Supported by NIH Grant 027103-1 to EB, NSF-EPSCoR Grant 0314742 to MU, McNeil Pharmaceuticals Grant 991-546-518 to EB and EW)