Vitamin E prevents renal dysfunction induced by experimental chronic bile duct ligation

M. Clara Ortiz, Melissa C. Manriquez, Karl A. Nath, Donna J. Lager, J. Carlos Romero, Luis A. Juncos

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Background. The mechanisms by which prolonged cholestasis alters renal hemodynamics and excretory function are unknown but may be related to increased oxidative stress, with subsequent formation of lipid peroxidation-derived products (e.g., F2-isoprostanes) and endothelin (ET). We investigated whether antioxidant therapy prevents chronic bile duct ligation (CBDL)-induced alterations in systemic and renal hemodynamics, and reduces F2-isoprostane and ET levels. Methods. Sprague-Dawley rats were placed on either a normal or a high vitamin E diet for 7 days and then underwent either CBDL or sham surgery. They were then maintained on their respective diets for 21 more days, at which time the physiologic studies were performed. Results. Thirty-three percent of the CBDL rats died by day 21. The remaining rats had a lower mean arterial pressure (MAP), renal blood flow (RBF), glomerular filtration rate (GFR), and sodium and water excretion than control rats. CBDL rats had higher portal pressure, renal venous pressure, and renal vascular resistance (RVR). These changes were associated with increased levels of systemic and renal venous F2-isoprostanes and ET. Vitamin E normalized MAP, RBF, GFR, RVR, and sodium and water excretion, and improved the 21-day survival without altering portal or renal venous pressures. Surprisingly, vitamin E did not alter the systemic levels of F2-isoprostanes but markedly reduced their levels in the renal venous circulation. Conclusion. Vitamin E improves MAP and renal function in CBDL rats, and selectively decreases renal levels of oxidative stress and ET, suggesting that local redox balance is implicated in CBDL-induced renal dysfunction.

Original languageEnglish (US)
Pages (from-to)950-961
Number of pages12
JournalKidney international
Volume64
Issue number3
DOIs
StatePublished - Sep 1 2003

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Keywords

  • F -isoprostanes
  • Hepatic cirrhosis
  • Hepatorenal syndrome
  • Kidney
  • Sodium retention

ASJC Scopus subject areas

  • Nephrology

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