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

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.