A role of liver fatty acid-binding protein in cisplatin-induced acute renal failure

Kidney Int. 2007 Aug;72(3):348-58. doi: 10.1038/sj.ki.5002304. Epub 2007 May 9.


Previous studies from our laboratory showed that increased fatty acid oxidation by the kidney is cytoprotective during cisplatin (CP)-mediated nephrotoxicity. In this study, we determined the effects of CP and fibrates on peroxisome proliferation and the expression of liver fatty acid-binding protein (L-FABP) in normal mice, and in mice transgenically overexpressing human L-FABP (h-L-FABP). Labeling of peroxisomes demonstrated reduced peroxisomal staining in the proximal tubule of CP-treated mice compared with control mice. There was increased peroxisomal labeling in the proximal tubules of both control and CP-treated mice when either was treated with fibrate; a known peroxisome proliferator-activated receptor-alpha ligand. L-FABP protein expression, not detected in control or CP-treated mice, was significantly increased in the proximal tubules of fibrate-treated mice of either group. In the transgenic mice, CP increased the shedding of h-L-FABP in the urine, which was decreased by fibrate as was the acute renal failure. A cytosolic pattern of h-L-FABP expression was found in the proximal tubules of untreated transgenic mice with a nuclear presence in CP-treated mice. Fibrate pretreatment restored the cytosolic expression pattern in CP-treated mice. Our study shows that fibrate may improve CP-induced acute renal failure due to both peroxisome proliferation and increased L-FABP in the cytosol of the proximal tubule.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acute Kidney Injury / chemically induced*
  • Acute Kidney Injury / metabolism
  • Acute Kidney Injury / physiopathology*
  • Animals
  • Biomarkers / metabolism
  • Cisplatin
  • Creatinine / blood
  • Fatty Acid-Binding Proteins / metabolism*
  • Gene Expression Regulation / physiology
  • Kidney Tubules / drug effects
  • Kidney Tubules / metabolism
  • Kidney Tubules / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mice, Transgenic
  • Peroxisome Proliferators / pharmacology*
  • Peroxisomes / physiology
  • Pyrimidines / pharmacology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism


  • Biomarkers
  • FABP1 protein, human
  • Fabp1 protein, mouse
  • Fatty Acid-Binding Proteins
  • Peroxisome Proliferators
  • Pyrimidines
  • RNA, Messenger
  • pirinixic acid
  • Creatinine
  • Cisplatin