title: Vitamin E ameliorates enhanced renal lipid peroxidation and accumulation of F2-isoprostanes in aging kidneys.
abstract: Aging results in progressive glomerular sclerosis and reductions in glomerular filtration rate (GFR). Oxidative stress may be an important mechanism for the aging process, but to date the role of oxidative stress on renal aging has not been determined. The present study was performed to determine whether age-related alterations in renal hemodynamics and morphology were associated with oxidative stress and whether this could be attenuated by chronic administration of vitamin E. Rats, aged 13 mo, were given either control diet containing vitamin E 50 IU/kg (n = 6) or a high-vitamin E diet (5,000 IU/kg; n = 6) for 9 mo. Another group of rats (3-4 mo old; n = 7) served as young controls. Aging was accompanied by a 60% reduction in GFR, a threefold increase in renal F2 isoprostanes, newly discovered vasoconstrictive F2-like prostaglandins generated by free radical-mediated lipid peroxidation. Renal aging was also associated with an increase in oxidant-sensitive heme oxygenase, advanced glycosylation end products (AGEs), and the AGE receptor, RAGE. AGE-RAGE interaction has been shown to induce oxidative stress. With high-vitamin E diet, GFR was increased by 50%, F2 isoprostanes were suppressed, and expression of heme oxygenase and RAGE was attenuated. There was also a tendency for glomerular sclerosis to be attenuated. These data demonstrate that age-related decline in renal function is accompanied by oxidative stress and that administration of antioxidants, such as vitamin E, could attenuate the decline in renal function.
authors.affiliation: Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson 39216, USA.
authors.forename: J F
authors.initials: JF
authors.lastname: Reckelhoff
authors.forename: V
authors.initials: V
authors.lastname: Kanji
authors.forename: L C
authors.initials: LC
authors.lastname: Racusen
authors.forename: A M
authors.initials: AM
authors.lastname: Schmidt
authors.forename: S D
authors.initials: SD
authors.lastname: Yan
authors.forename: J
authors.initials: J
authors.lastname: Marrow
authors.forename: L J
authors.initials: LJ
authors.lastname: Roberts
authors.forename: A K
authors.initials: AK
authors.lastname: Salahudeen
mesh_terms: D000375:Aging; D000818:Animals; D015237:Dinoprost / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D051547:Heme Oxygenase-1; D006439:Hemodynamics; D007668:Kidney / Q000098:blood supply / Q000378:metabolism*; D008054:Lipid Peroxides / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000502:physiology; D014810:Vitamin E / Q000097:blood / Q000494:pharmacology*
chemical_list: D017127:Glycation End Products, Advanced; D008054:Lipid Peroxides; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D014810:Vitamin E; D015237:Dinoprost; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1