Tryptophan intake, not always the more the better

Area of Science:

• Biochemistry
• Toxicology
• Nephrology

Background:

• Tryptophan is an essential amino acid with complex metabolic pathways.
• The aryl hydrocarbon receptor (AhR) pathway plays a role in cellular responses to environmental stimuli.
• Understanding the impact of excessive tryptophan on kidney health is crucial.

Purpose of the Study:

• To investigate the adverse effects of excessive tryptophan intake on kidney function.
• To examine the role of the tryptophan metabolism-related aryl hydrocarbon receptor (AhR) pathway in tryptophan-induced kidney injury.
• To compare these effects in healthy rats and rats with chronic kidney disease (CKD).

Main Methods:

• Administered varying doses of tryptophan to healthy rats and CKD rats for 12 and 8 weeks, respectively.
• Assessed renal function (serum creatinine, BUN), kidney pathology (H&E staining), and AhR pathway activation (serum/kidney AhR, CyP1A1, CyP1B1 levels).
• Utilized UHPLC-MRM-MS to quantify tryptophan metabolites in both experimental groups.

Main Results:

• High tryptophan diets increased BUN and induced renal tubulointerstitial injury in healthy rats.
• Excessive tryptophan significantly increased mortality, serum creatinine, BUN, and renal damage in CKD rats.
• Elevated levels of kynurenine, indole metabolites, and AhR pathway markers were observed in rats with high tryptophan intake.

Conclusions:

• Excessive tryptophan intake leads to the accumulation of detrimental kynurenine and indole metabolites.
• The aryl hydrocarbon receptor (AhR) pathway is activated by excessive tryptophan, contributing to kidney injury.
• While moderate tryptophan may be beneficial, excessive intake poses significant risks to kidney health.