The protective effect of alpha-tocopherol against dichromate-induced renal tight junction damage is mediated via ERK1/2

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 (Cr6-) toxicity. We evaluated whether co-administration of the antioxidant alpha-tocopherol (alpha-TOC) prevents Cr6+ toxicity in TJ Female Wistar rats received potassium dichromate 15 mg/kg, sc (5 3 mg/kg of Cr6+) single dose. with or without alpha-TOC (125 mg/kg. po. daily). Two and 7 days after Cr6+ 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 Cr6+ 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 Cr6+-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 Cr6+-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 (C) 2009 Elsevier Ireland Ltd. All rights reserved