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Am J Physiol Regul Integr Comp Physiol 274: R767-R774, 1998;
0363-6119/98 $5.00
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Vol. 274, Issue 3, R767-R774, March 1998

Vitamin E ameliorates enhanced renal lipid peroxidation and accumulation of F2-isoprostanes in aging kidneys

Jane F. Reckelhoff1, Vijaya Kanji2, Lorraine C. Racusen3, Ann Marie Schmidt4, Shu Du Yan4, Jason Morrow5, L. Jackson Roberts II5, and Abdulla K. Salahudeen2

Departments of 1 Physiology and Biophysics and 2 Nephrology, University of Mississippi Medical Center, Jackson, Mississippi 39216; 3 Department of Pathology, Johns Hopkins University, Baltimore, Maryland 21205; 4 Department of Medicine, Surgery and Pathology, Columbia University, College of Physicians and Surgeons, New York, New York 10032; and 5 Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232

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.

glomerular filtration rate; free radicals; advanced glycosylation end products; heme oxygenase


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