Table 1.
Effects of tryptophan and its metabolism via the kynurenine pathway in solid organ IRI in animal models.
| Reference | Experimental Model | Treatment/Intervention | Outcomes |
|---|---|---|---|
| Peng et al. [45], 2012 | Mice kidney IRI model | Tryptophan deficient diet for 6 days before induction of kidney or liver ischemia. | ↓serum creatinine and urea 1 day after bilateral renal ischemia-reperfusion; ↓expression of KIM-1 mRNA; ↓level of acute tubular necrosis in histology; ↓serum levels of ALT, AST, LDH after liver ischemia-reperfusion; ↓P-selectin and IL-6 gene expression; ↓number of circulating neutrophils. Effect dependent on GCN2. |
| Liu et al. [28], 2007 | Rats model of lung Tx after 5 h of warm ischemia | Sleeping beauty transposon mediated hIDO gene delivery to donor animals intravenously 24 h prior to Tx. | ↓apoptosis of endothelial cells; ↓leukocyte infiltration; ↑antioxidant capacity; ↓levels of oxidative stress markers (protein carbonyl, MDA); ↓alveolar edema, hemorrhage and formation of focal congestion of lung tissue; preserved mitochondrial structure and function; ↓peak airway pressure, ↑PaO2. |
| Mohib et al. [52], 2008 | Mice kidney IRI model | IDO gene knock-out or IDO inhibition by intraperitoneal injections of 3 mg of 1-MT twice a day for 48 h following reperfusion. Some mice received 1-MT 1 h before ischemia, as well as following reperfusion. | ↓serum creatinine and blood urea nitrogen in IDO-knockout mice; ↓blood urea nitrogen but no difference in serum creatinine in 1-MT-treated mice; preserved architecture of kidney tissue; ↓apoptosis and necrosis; ↓neutrophil infiltration in IDO-knockout and 1-MT treated mice. |
| Merchen et al. [53], 2014 | Rats kidney IRI model | IDO inhibition by pretreating rats with 1-MT 140 mg/kg po 1 and 24 h prior to renal ischemia. | IRI alone changed 105 coding genes and 3 noncoding RNA transcripts. In IRI rats pretreated with 1-MT, altered coding transcripts declined to 18 sequences and altered noncoding RNA genes increased to 66. |
| Zheng et al. [25], 2019 | Mice kidney IRI model | KMO gene knockout. | ↓plasma creatinine; ↓tubular damage; ↓number of apoptotic cells; ↓neutrophil infiltration; ↓Cxcl 1 and Cxcl2 mRNA levels in kidney tissue. |
| Wang et al. [62], 2019 Li et al. [63], 2020 |
Rats liver IRI mode | Intraperitoneal administration of L-NAT (10 mg/kg) 30 min before ischemia. | ↓IRI-induced histological changes in hepatocytes; ↓mRNA expression of RIP2, caspase-1 and IL-1b [62]; ↓caspase-1 activity and IL-1b expression; ↓expression of autophagy markers: LC3-II, Beclin1, and ATG-7 and ↑expression of P62; ↓formation of autophagosome; improved morphological and functional changes of mitochondria, maintained the quantity and quality of mtDNA stability; ↓excessive mitophagy [63]. |
Abbreviations: IRI: ischemia-reperfusion injury, Tx: transplantation, (h)IDO: (human) indoleamine-2,3-dioxygenase, KMO: kynurenine-3-monooxygenase, 1-MT: 1-metyltryptophan, L-NAT: N-acetyl-l-tryptophan, KIM: kidney injury molecule, ALT: alanyl aminotransferase, AST: aspartate aminotransferase, LDH: lactate dehydrogenase, IL: interleukin, GCN2: general control nonderepressible 2 kinase, MDA: malondialdehyde, PaO2: partial oxygen pressure, (m)RNA: (messenger) RNA, Cxcl: reduced chemokine (C-X-C motif) ligand, RIP: receptor interacting protein, LC3-II: microtubule-associated protein 1 light chain 3-II, ATG-7: autophagy-related protein-7 and mtDNA: mitochondrial DNA, ↑: increased, ↓: decreased.