title: Alpha-tocopherol protects against the renal damage caused by potassium dichromate.
abstract: Exposure to hexavalent chromium (Cr(6+)) causes mutagenic, carcinogenic, and toxic effects, some of which have been associated with its oxidative capacity. In the kidney, Cr(6+) has been claimed to provoke necrosis of the proximal tubular cells. Our aim was to assess the functional involvement of the different segments that form the nephron in a model of acute renal failure caused by potassium dichromate and the participation of oxidative damage in this process. We also studied the possible protective effect of alpha-tocopherol (alpha-TOC) against renal damage. Wistar female rats 200g body weight (bw) received potassium dichromate (15mg/kg, sc, single dose). Lipid peroxidation and renal function were evaluated on days 0, 1, 2, 3, 7, 10, and 14. A second group received alpha-TOC (125mg/kg, by gavage) 5 days before and during dichromate exposure (same dose as for the first group), and was monitored at 0, 2, and 7 days of exposure. Creatinine clearance, glucose and sodium fractional excretions, p-aminohippurate uptake, free-water and osmolal clearances were also measured. Thiobarbituric acid-reactive substances were quantified in renal cortex. The results revealed altered proximal tubule function, decreased glomerular filtration, and distal segment dysfunction, accompanied by oxidative damage 48h after exposure to dichromate. In the alpha-TOC-treated group proximal reabsorptive and secretory functions were preserved, suggesting that oxidative damage is a participating mechanism in dichromate toxicity on these functions. In contrast alpha-TOC did not prevent glomerular or distal dysfunction, indicating selectivity of the protection afforded by this compound on the toxicity of dichromate, at the several components of the nephron.
authors.affiliation: Sección Externa de Toxicología, Cinvestav, Ave IPN #2508, Col. San Pedro Zacatenco, Mexico, DF 07360, Mexico.
authors.forename: Laura
authors.initials: L
authors.lastname: Arreola-Mendoza
authors.forename: José L
authors.initials: JL
authors.lastname: Reyes
authors.forename: Estela
authors.initials: E
authors.lastname: Melendez
authors.forename: Dolores
authors.initials: D
authors.lastname: Martín
authors.forename: Maria C
authors.initials: MC
authors.lastname: Namorado
authors.forename: Elsa
authors.initials: E
authors.lastname: Sanchez
authors.forename: Luz M
authors.initials: LM
authors.lastname: Del Razo
mesh_terms: D000818:Animals; D003404:Creatinine / Q000097:blood / Q000652:urine; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D007686:Kidney Tubules, Distal / Q000187:drug effects / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D011192:Potassium Dichromate / Q000633:toxicity*; D020011:Protective Agents / Q000494:pharmacology*; D011507:Proteinuria / Q000139:chemically induced / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D024502:alpha-Tocopherol / Q000494:pharmacology*
chemical_list: D020011:Protective Agents; D017392:Thiobarbituric Acid Reactive Substances; D003404:Creatinine; D024502:alpha-Tocopherol; D011192:Potassium Dichromate