The protective effect of 1-methyltryptophan isomers in renal ischemia-reperfusion injury is not exclusively dependent on indolamine 2,3-dioxygenase inhibition

Indolamine 2,3-dioxygenase (IDO), an enzyme that catalyses the metabolism of tryptophan, may play a detrimental role in ischemia-reperfusion injury (IRI). IDO can be inhibited by 1-methyl-tryptophan, which exists D (D-MT) or L (L-MT) isomer. These forms show different pharmacological effects besides inhibition. Therefore, we sought to investigate whether these isomers protective renal IRI, either IDO-dependent independent. We studied effect both rat IRI model with focus on and independent effects. Both MT reduced creatinine BUN levels, D-MT having faster onset action but shorter duration L-MT slower longer (24 h 48 vs 96 reperfusion time). Interestingly, this was not exclusively dependent inhibition, rather from decreased TLR4 signalling, mimicking changes function. Additionally, increased overall survival rats. Moreover, interfered TGF-? signalling epithelial-mesenchymal transition. In order study all mechanisms involved series vitro experiments performed. The affected pathways NK cells tubular epithelial cells, as well dendritic T cells. This shows have renoprotective after injury, mostly involving mutually mechanisms. bring novel findings properties mechanism isomers, could become therapeutic target IRI.