Pre-administration of L-tryptophan improved ADR-induced early renal failure in mice

Life Sci. 2012 Aug 21;91(3-4):100-6. doi: 10.1016/j.lfs.2012.06.018. Epub 2012 Jun 28.

Abstract

Aims: The aim of this study was to determine the localization of the rate-limiting enzyme indoleamine 2, 3-dioxygenase (IDO) and its metabolite in mice kidneys after adriamycin (ADR)-induced renal failure. We also examined the effect of L-tryptophan (Trp) administration on this model.

Main methods: BALB/c mice were treated with 15 mg/kg ADR to induce renal failure. The change of IDO and L-kynurenine (Kyn) following ADR-induced renal failure was examined by immunostaining combined with hematoxylin and eosin (HE) and Periodic acid-Schiff (PAS) staining for morphological analysis, and the concentration of L-Kyn was measured by HPLC. The effect of L-Trp administration on ADR-induced renal failure was also investigated.

Key findings: Time-dependent increase of IDO immunostaining was observed in tubular cells from Day 4 after ADR injection. It was found that mice fed with L-Trp had less chance of renal failure at four days after ADR injection than mice untreated with L-Trp, but not at seven days. Further, L-Trp treatment significantly suppressed an increased level of TNF-alpha mRNA, but not of TGF-beta and IL1-beta after renal injury.

Significance: Local IDO expression in tubules was induced markedly after ADR- induced renal failure. L-Trp administration can be effective in suppressing ADR-induced renal failure at an early stage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromatography, High Pressure Liquid / methods
  • Down-Regulation
  • Doxorubicin / adverse effects
  • Eosine Yellowish-(YS) / pharmacology
  • Hematoxylin / pharmacology
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / pharmacology*
  • Kidney / metabolism
  • Kynurenine / pharmacology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Periodic Acid / pharmacology
  • RNA, Messenger / metabolism
  • Renal Insufficiency / drug therapy*
  • Schiff Bases / pharmacology
  • Time Factors
  • Tryptophan / administration & dosage*

Substances

  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • RNA, Messenger
  • Schiff Bases
  • Periodic Acid
  • Kynurenine
  • Doxorubicin
  • Tryptophan
  • Eosine Yellowish-(YS)
  • Hematoxylin