title: Effect of short-term, low dose aspirin supplementation on the activation of pro-inflammatory NF-kappaB in aged rats.
abstract: The basis of our recently proposed "molecular inflammation theory of aging" is that activated inflammatory transcription factors, including versatile NF-kappaB, occur widespread in the organism during aging. NF-kappaB plays a key role in pro-inflammatory gene expression, such as cyclooxygenase (COX). Aspirin is one of the most commonly used non-steroidal anti-inflammatory drugs because of its ability to inhibit COX activity. Thus, in the present study, we investigated the effect of short-term, low dose aspirin intake on the modulation of pro-inflammatory NF-kappaB activation in old rats. To conduct the study, 24-month-old Fischer 344 rats were supplemented with low dose aspirin (0.015%) for 10 days. Biochemical analyses showed suppressed reactive species (RS) and COX-2 activity. The data also showed that NF-kappaB activation and its associated gene expressions, such as COX-2, iNOS, VCAM-1 and ICAM-1, were all suppressed by the low dose aspirin supplementation through the inhibition of phosphorylation and degradation of IkappaBalpha via the NIK/IKK pathway. Our molecular exploration further revealed that aspirin's suppressive action of NF-kappaB was mediated by its ability to inhibit the nuclear translocation of cytosolic thioredoxin and redox factor-1. These findings showed for the first time that in aged rat short-term low dose dietary aspirin feeding modulates the molecular signal transduction involved in the inflammatory process.
authors.affiliation: Department of Pharmacy, College of Pharmacy, Aging Tissue Bank, Pusan National University, Gumjung-gu, Busan 609 735, Republic of Korea.
authors.forename: Kyung Jin
authors.initials: KJ
authors.lastname: Jung
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Yani
authors.initials: Y
authors.lastname: Zou
authors.forename: You Jung
authors.initials: YJ
authors.lastname: Kim
authors.forename: Byung Pal
authors.initials: BP
authors.lastname: Yu
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Chung
mesh_terms: D000375:Aging / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D001241:Aspirin / Q000008:administration & dosage*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016328:NF-kappa B; D001241:Aspirin