title: Chronic paracetamol treatment influences indices of reactive oxygen species accumulation in the aging Fischer 344 X Brown Norway rat aorta.
abstract: Previous reports have demonstrated that increased levels of reactive oxygen species (ROS) and alterations in cell signaling characterize aging in the Fischer 344 X Brown Norway (FBN) rat aorta. Other work has suggested that increases in ROS may be related to vascular wall thickening and the development of hypertension. Paracetamol (acetaminophen) is a potent antioxidant that has been found to diminish free radicals in ischemia-reperfusion studies. However, it remains unclear whether chronic paracetamol administration influences signaling or ROS accumulation in the aging aorta. FBN rats (27 months old; n=8) were subjected to 6 months of treatment with a therapeutic dose of paracetamol (30 mg/kg/day) and compared to age-matched untreated FBN rat controls (n=8). Compared to measurements in the aortae of 6-month old animals, tunica media thickness, tissue superoxide levels, and protein oxidation levels were 38 ± 7%, 92 ± 31%, and 7 ± 2% higher in the aortae of 33-month control animals (p ≤0.05). Chronic paracetamol treatment decreased tunica media thickness and the amount of oxidized protein by 13 ± 4% and 30 ± 1%, respectively (p ≤0.05). This finding of diminished aortic thickening was associated with increased phosphorylation (activation) of the mitogen activated protein kinases and diminished levels of the anti-apoptotic protein Bcl-2. Taken together, these data suggest that chronic paracetamol treatment may decrease the deleterious effects of aging in the FBN rat aorta.
authors.affiliation: Center for Diagnostic Nanosystems, Marshall University, Huntington WV 25755, USA.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Rice
authors.forename: Sarath
authors.initials: S
authors.lastname: Meduru
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Kakarla
authors.forename: Anjaiah
authors.initials: A
authors.lastname: Katta
authors.forename: Sriram P
authors.initials: SP
authors.lastname: Mupparaju
authors.forename: Brent
authors.initials: B
authors.lastname: Kidd
authors.forename: Lynne J
authors.initials: LJ
authors.lastname: Goebel
authors.forename: Eric R
authors.initials: ER
authors.lastname: Blough
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage* / Q000494:pharmacology*; D000263:Adenylate Kinase / Q000378:metabolism; D000375:Aging / Q000187:drug effects*; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D003433:Crosses, Genetic; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D000082:Acetaminophen; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D000263:Adenylate Kinase