Tryptophan toxicity--time and dose response in rats

Area of Science:

• Biochemistry
• Toxicology
• Pathology

Background:

• L-tryptophan (Trp) ingestion has been linked to eosinophilia myalgia syndrome (EMS).
• A contaminant, 1,1'-ethylidene-bis-L-tryptophan, was implicated in EMS epidemics.
• Metabolic abnormalities of Trp are observed in other syndromes like carcinoid syndrome and scleroderma.

Purpose of the Study:

• To investigate the role of L-tryptophan (Trp) or its metabolites in inducing tissue damage.
• To examine the effects of different Trp dosing regimens on tissue pathology.
• To assess the impact of kynurenine pathway induction on Trp-induced damage.

Main Methods:

• Female rats were fed diets supplemented with 1%, 2%, or 5% Trp for 3, 6, or 12 weeks.
• Para-chlorophenyl alanine (p-CPA), a Trp hydroxylase inhibitor, was administered to induce kynurenine pathway activation.
• Body weight, mortality, skin changes, and tissue histology (lung, spleen, muscle) were assessed.

Main Results:

• Higher Trp levels slowed body weight gain; p-CPA injection caused weight loss and mortality in some Trp-fed rats.
• Alopecia and skin alterations were observed post-p-CPA treatment in Trp-fed animals.
• Increased connective tissue and inflammatory cell proliferation occurred in multiple organs, exacerbated by p-CPA-induced kynurenine pathway activation.

Conclusions:

• Excessive L-tryptophan (Trp) or its elevated metabolites may contribute to pathological features of eosinophilia myalgia syndrome (EMS).
• Kynurenine pathway metabolites can amplify Trp-induced tissue damage.
• This research highlights the potential toxicity of high Trp intake and its metabolic pathways.