The protective effect of alpha-tocopherol against dichromate-induced renal tight junction damage is mediated via ERK1/2.
Toxicol Lett
; 191(2-3): 279-88, 2009 Dec 15.
Article
em En
| MEDLINE
| ID: mdl-19766176
Renal tight junctions (TJ) play a central role in modulating the paracellular pathway. We examined the function, quantity and distribution of TJ proteins: occludin and claudin-2 (cln-2), on proximal tubule in a model of acute renal failure (ARF) associated with oxidative damage. Since ERK1/2-p modulates TJ integrity, we studied their participation in dichromate (Cr(6+)) toxicity. We evaluated whether co-administration of the antioxidant alpha-tocopherol (alpha-TOC) prevents Cr(6+) toxicity in TJ. Female Wistar rats received potassium dichromate 15 mg/kg, s.c. (5.3 mg/kg of Cr(6+)) single dose, with or without alpha-TOC (125 mg/kg, p.o., daily). Two and 7 days after Cr(6+) treatment, oxidative damage was assessed by renal lipid peroxidation (LPO), proximal function was estimated by sodium and glucose fractional excretions. Occludin, cln-2, and ERK1/2-p were detected by immunofluorescence and Western blot. ARF induced by Cr(6+) provoked augment in the sodium and glucose urinary looses, increases in occludin quantity (6.6- and 15-fold on days 2 and 7, respectively) and the mislocation of cln-2. Electrophoresis migration showed a higher molecular weight band only in the Cr(6+)-administered groups, suggesting occludin hyperphosphorylation. Alpha-TOC treatment diminished the LPO, improved tubular function, and preserved TJ location and expression. In summary, we show disruption of occludin and cln-2 in ARF induced by Cr(6+)-intoxication. This study provides evidence of the beneficial effect of alpha-TOC on TJ structure and function undergoing oxidative damage, and we suggest the participation of ERK1/2 in the mechanisms leading to protection by the antioxidant.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cromatos
/
Junções Íntimas
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Proteína Quinase 1 Ativada por Mitógeno
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Alfa-Tocoferol
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Proteína Quinase 3 Ativada por Mitógeno
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Antioxidantes
Limite:
Animals
Idioma:
En
Revista:
Toxicol Lett
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
México
País de publicação:
Holanda