# Renoprotection by 5-Methoxytryptophan in Kidney Disease

**Authors:** Jonah P. Gutierrez, Tram N. Diep, Shaona Niu, Liang-Jun Yan

PMC · DOI: 10.3390/biom16020223 · Biomolecules · 2026-02-02

## TL;DR

This paper reviews how 5-methoxytryptophan (5-MTP) protects the kidneys from injury and could be a potential treatment for kidney disease.

## Contribution

The paper highlights 5-MTP as a novel therapeutic and biomarker for chronic kidney disease.

## Key findings

- 5-MTP levels are reduced in chronic kidney disease patients, suggesting its role as a biomarker.
- Exogenous 5-MTP shows nephroprotective effects in multiple rodent models of kidney injury.
- 5-MTP protects kidneys through antioxidative, anti-inflammatory, and anti-fibrotic mechanisms.

## Abstract

Kidney disease, be it acute or chronic, has a complex pathology and is a significant human health problem. Increasing interest has been focused on exploring therapeutic targets that can be used to safeguard kidney function under a variety of detrimental conditions. In this article, we review the protective effects of 5-methoxytryptophan (5-MTP), a tryptophan metabolite, on kidney injury. Published studies indicate that serum 5-MTP level is decreased in patients with chronic kidney disease (CKD), suggesting that 5-MTP is a biomarker for CKD and has therapeutic values. Indeed, rodent models of kidney injury induced by folic acid, lipopolysaccharide (LPS), unilateral ureteral obstruction (UUO), and ischemia/reperfusion all demonstrate that exogenous 5-MTP exhibits nephroprotective effects. The underlying mechanisms involve antioxidative damage via activating antioxidant systems such as heme oxygenase-1, anti-inflammation, anti-fibrosis, and enhanced mitophagy. To further explore the underlying mechanisms and the potential of 5-MTP as a kidney therapeutic compound, future studies need to include more rodent models of kidney injury induced by a variety of insults. Moreover, how to boost endogenous 5-MTP content and its potential synergistic effects with other therapeutic approaches aiming to combat kidney diseases also remain to be explored.

## Linked entities

- **Chemicals:** 5-methoxytryptophan (PubChem CID 119802), folic acid (PubChem CID 135398658)
- **Diseases:** chronic kidney disease (MONDO:0005300)

## Full-text entities

- **Genes:** SOD1 (superoxide dismutase 1) [NCBI Gene 6647] {aka ALS, ALS1, HEL-S-44, IPOA, SOD, STAHP}, ASMT (acetylserotonin O-methyltransferase) [NCBI Gene 438] {aka ASMTY, HIOMT, HIOMTY}, Hmox1 (heme oxygenase 1) [NCBI Gene 15368] {aka D8Wsu38e, HO-1, HO1, Hemox, Hmox, Hsp32}, AVP (arginine vasopressin) [NCBI Gene 551] {aka ADH, ARVP, AVP-NPII, AVRP, VP}, NADK (NAD kinase) [NCBI Gene 65220] {aka NADK1, dJ283E3.1}, NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 4780] {aka IMDDHH, NRF2, Nrf-2}, WEE1 (WEE1 G2 checkpoint kinase) [NCBI Gene 7465] {aka WEE1A, WEE1hu}, CX3CL1 (C-X3-C motif chemokine ligand 1) [NCBI Gene 6376] {aka ABCD-3, C3Xkine, CXC3, CXC3C, NTN, NTT}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, CAT (catalase) [NCBI Gene 847], COX2 (cytochrome c oxidase subunit II) [NCBI Gene 4513] {aka COII, MTCO2}, Tlr2 (toll-like receptor 2) [NCBI Gene 24088] {aka Ly105}, CD38 (CD38 molecule) [NCBI Gene 952] {aka ADPRC 1, ADPRC1, cADPR1}, CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347] {aka GDCF-2, HC11, HSMCR30, MCAF, MCP-1, MCP1}, TSTD1 (thiosulfate sulfurtransferase like domain containing 1) [NCBI Gene 100131187] {aka KAT}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, Tgfb1 (transforming growth factor, beta 1) [NCBI Gene 21803] {aka TGF-beta1, TGFbeta1, Tgfb, Tgfb-1}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, IL1A (interleukin 1 alpha) [NCBI Gene 3552] {aka IL-1 alpha, IL-1A, IL1, IL1-ALPHA, IL1F1}, Nfe2l2 (nuclear factor, erythroid derived 2, like 2) [NCBI Gene 18024] {aka Nrf2}, PTGS2 (prostaglandin-endoperoxide synthase 2) [NCBI Gene 5743] {aka COX-2, COX2, GRIPGHS, PGG/HS, PGHS-2, PHS-2}, TDO2 (tryptophan 2,3-dioxygenase) [NCBI Gene 6999] {aka HYPTRP, TDO, TO, TPH2, TRPO}, NOX4 (NADPH oxidase 4) [NCBI Gene 50507] {aka KOX, KOX-1, RENOX}, DLD (dihydrolipoamide dehydrogenase) [NCBI Gene 1738] {aka DLDD, DLDH, E3, GCSL, LAD, OGDC-E3}, MAP1LC3A (microtubule associated protein 1 light chain 3 alpha) [NCBI Gene 84557] {aka ATG8E, LC3, LC3A, MAP1ALC3, MAP1BLC3}, QPRT (quinolinate phosphoribosyltransferase) [NCBI Gene 23475] {aka HEL-S-90n, QPRTase}, LAT (linker for activation of T cells) [NCBI Gene 27040] {aka IMD52, LAT1, pp36}, CXCL12 (C-X-C motif chemokine ligand 12) [NCBI Gene 6387] {aka IRH, PBSF, SCYB12, SDF1, TLSF, TPAR1}, ACE2 (angiotensin converting enzyme 2) [NCBI Gene 59272] {aka ACEH}, REN (renin) [NCBI Gene 5972] {aka ADTKD4, HNFJ2, RTD}, EPO (erythropoietin) [NCBI Gene 2056] {aka DBAL, ECYT5, EP, MVCD2}, DDC (dopa decarboxylase) [NCBI Gene 1644] {aka AADC}, PI3 (peptidase inhibitor 3) [NCBI Gene 5266] {aka ESI, SKALP, WAP3, WFDC14, cementoin}, IDO1 (indoleamine 2,3-dioxygenase 1) [NCBI Gene 3620] {aka IDO, IDO-1, INDO}, HMOX1 (heme oxygenase 1) [NCBI Gene 3162] {aka HMOX1D, HO-1, HSP32, bK286B10}, PTH (parathyroid hormone) [NCBI Gene 5741] {aka FIH1, PTH1}, IL13 (interleukin 13) [NCBI Gene 3596] {aka IL-13, P600}, PRDX5 (peroxiredoxin 5) [NCBI Gene 25824] {aka ACR1, AOEB166, B166, HEL-S-55, PLP, PMP20}
- **Diseases:** atrophy (MESH:D001284), CKD (MESH:D051436), toxicity (MESH:D064420), Cerebrovascular Injury (MESH:D002561), gut leak (MESH:D019559), tumor (MESH:D009369), /R) injury (MESH:C580424), ischemic stroke (MESH:D002544), diabetes (MESH:D003920), decreased cardiac output (MESH:D002303), CKF (MESH:D007676), ischemic (MESH:D002545), infections (MESH:D007239), renal failure (MESH:D051437), brain injury (MESH:D001930), hypertension (MESH:D006973), rhabdomyolysis (MESH:D012206), hyperglycemia (MESH:D006943), Albuminuria (MESH:D000419), I/R (MESH:D015427), Fibrosis (MESH:D005355), glomerulosclerosis (MESH:D005921), Inflammation (MESH:D007249), shock (MESH:D012769), anemia (MESH:D000740), injury to (MESH:D014947), hypoxia (MESH:D000860), Sepsis (MESH:D018805), Tissue (MESH:D017695), UUO (MESH:D014517), septic (MESH:D001170), Renal Ischemia/Reperfusion Injury (MESH:D007511), DKD (MESH:D003928), vitamin D deficiency (MESH:D014808), AKI (MESH:D058186), Kidney injury (MESH:D007674), organ failures (MESH:D009102), T2D (MESH:D003924)
- **Chemicals:** MDA (MESH:D008315), 5-methoxyindole-2-carboxylic acid (MESH:C008400), amino acid (MESH:D000596), isoleucine (MESH:D007532), NADP+ (MESH:D009249), 5-MTP (MESH:C027986), kynurenic acid (MESH:D007736), Hematoxylin (MESH:D006416), vitamin D (MESH:D014807), 5-hydroxyindole acetic acid (MESH:D006897), melatonin (MESH:D008550), superoxide (MESH:D013481), 2,7-dicholorofluorescin (-), hydrogen peroxide (MESH:D006861), methionine (MESH:D008715), heavy metals (MESH:D019216), folic acid (MESH:D005492), ROS (MESH:D017382), 8-oxo-deoxyguanosine (MESH:D000080242), 5-methoxyindole (MESH:C487413), glucose (MESH:D005947), creatinine (MESH:D003404), serotonin (MESH:D012701), indole acetic acid (MESH:C030737), thiobarbituric acid reactive substances (MESH:D017392), kynurenine (MESH:D007737), adenine (MESH:D000225), Tryptophan (MESH:D014364), NAD+ (MESH:D009243), eosin (MESH:D004801), 5-HTP (MESH:D006916), lipid (MESH:D008055), urea nitrogen (MESH:C530477), LPS (MESH:D008070), glutathione (MESH:D005978), ATP (MESH:D000255)
- **Species:** Homo sapiens (human, species) [taxon 9606], Rodentia (rodent, order) [taxon 9989], Mus musculus (house mouse, species) [taxon 10090], Rattus norvegicus (brown rat, species) [taxon 10116]

## Full text

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## References

139 references — full list in the complete paper: https://tomesphere.com/paper/PMC12938402/full.md

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Source: https://tomesphere.com/paper/PMC12938402