Tryptophan ? niacin pathway in scleroderma and in dermatomyositis

Binazzi, M; Calandra, P

doi:10.1007/bf00595531

Cited by 14 publications

(5 citation statements)

References 3 publications

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“…Additional cases of SSc-like illness were reported after exposure to 5-HTP, carbidopa, 108 and other alterations in tryptophan metabolism. [109][110][111] Anecdotal reports of SSc-like cutaneous disease were described with appetite suppressants (eg, dexamphetamine), 112 pentazocine, 113,114 penicillamine, 115 bromocriptine, 116 methylphenidate, 117 local anesthetic, 118 and estrogen. 119,120 Vitamin K injection has been associated with a morphea-like reaction, Texier's disease.…”

Section: Chemotherapeutic Agentsmentioning

confidence: 99%

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Toward Understanding of Environmental Risk Factors in Systemic Sclerosis

et al. 2020

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Importance Systemic sclerosis (SSc) is a severe, chronic, and incurable autoimmune fibrotic skin disease with significant extracutaneous involvement. Low concordance rate in twin studies and unequal geographic distribution of SSc argues for importance of environment in disease initiation and progression. Objective In this manuscript we provide a summary of all investigated potential external risk factors for SSc. Data sources A literature search in PubMed and EMBASE database was performed for studies published until January 1, 2020 by 2 reviewers (EN and LO) independently. Findings Occupational and/or environmental exposures to silica and organic solvents are associated with increased incidence and severity of SSc. Exposure to epoxy resins, asbestos, and particulate air pollution favors increased risk of SSc, but data are based on limited number of observational studies. There is insufficient evidence to conclude an association between SSc development and other occupational (eg, welding fumes) or personal exposures (eg, smoking, vitamin D deficiency). Association of SSc with silicone breast implants has been disproven. Infectious pathogens (eg, Helicobacter pylori and angiotropic viruses) and dysbiosis seem to play a role in SSc development and severity, but their role remains to be clarified. Conclusions and relevance It may be prudent to counsel our patients with SSc (or those at risk of SSc) to avoid occupations with exposure to silica, organic solvents, asbestos and epoxy resins; restraint from smoking, using cocaine or drugs with pro-fibrotic potential. While the association between low vitamin D and SSc remains to be confirmed, we believe that SSc patients should be encouraged to maintain healthy vitamin D levels as benefits outweigh the risks.

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Section: Chemotherapeutic Agentsmentioning

confidence: 99%

“…Additional cases of SSc-like illness were reported after exposure to 5-HTP, carbidopa, 108 and other alterations in tryptophan metabolism. 109 -111…”

Section: Exposures With Probable Association (Level III Evidence)mentioning

confidence: 99%

Toward Understanding of Environmental Risk Factors in Systemic Sclerosis

et al. 2020

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“…Excretion of TRP, KYN, and KYNA in the urine was not studied in our study. Since previous publications indicate increased urinary excretion of KYN and KYNA in SSc patients [10][11][12], it cannot be excluded that the results of measuring the current level of KP metabolites in the blood do not provide a complete picture of the processes occurring in the affected tissues. Considering that KYN excretion is increased, and yet the KYN level in the blood does not change, as is the case in women with SSc, it can be presumed that KYN production is in fact elevated, at least by an amount to compensate for increased urine excretion of KYN.…”

Section: Study Limitationsmentioning

confidence: 99%

“…To this end, the main aim of this study is to examine the sex-related differences in the KP in SSc patients considering the peripheral concentrations of TRP, KYNA, and KYN as well as kynurenine pathway enzyme activity indicators, indoleamine 2,3-dioxygenase In recent decades, there has been increasing discussion about the role of KP metabolites in SSc [5][6][7], as these metabolites are closely associated with inflammation [8]. Previous studies in SSc patients have shown an increase in the urinary excretion of certain TRP metabolites, particularly kynurenine (KYN), which allowed formulation of the hypothesis regarding dysregulation of TRP metabolism in SSc [9][10][11][12]. Furthermore, other studies revealed that metabolites of TRP formed along KP, specifically KYN and kynurenic acid (KYNA), have been found to inhibit fibroblast metabolism and proliferation and alleviate fibrosis [13,14].…”

Section: Introductionmentioning

confidence: 99%

Different Kynurenine Pathway Dysregulation in Systemic Sclerosis in Men and Women

Turska-Kozłowska,

Pedraz-Petrozzi,

Paluszkiewicz

et al. 2024

IJMS

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Systemic sclerosis (SSc), a predominantly female-affected systemic autoimmune disease, requires tailored treatment strategies contingent on organ involvement and symptom severity. Given SSc’s inflammatory nature, the involvement of the kynurenine pathway (KP) in its pathophysiology is underexplored. Our study aimed to investigate sex-related differences in KP activation among SSc patients and assess the impact of angiotensin-converting enzyme (ACE) inhibitors and estimated glomerular filtration rate (eGFR) on KP metabolite concentrations. We enrolled 48 SSc patients and 53 healthy controls, quantifying KP metabolites (tryptophan (TRP), kynurenine (KYN), and kynurenic acid (KYNA)) in serum via high-performance liquid chromatography. Separate multivariate analyses of covariance (MANCOVAs) for women and men were performed to ascertain mean differences between patients and healthy controls while correcting for age. For our secondary objective, we conducted a MANCOVA to explore disparities in ACE inhibitor users and non-users among patients, with BMI correction. Our findings revealed decreased TRP concentrations but increased KYNA/TRP ratio and KYN/TRP ratio in both male and female SSc patients compared to their respective controls. Unlike women, SSc males exhibited higher KYN concentrations and decreased KYNA/KYN ratio relative to their controls. Additionally, SSc patients using ACE inhibitors had higher serum KYNA levels than non-users. Notably, we established a significant correlation between eGFR and KYNA in SSc patients. These results indicate differential KP activation in male and female SSc patients, with males demonstrating heightened KP activation. While ACE inhibitors may influence the KP in SSc patients, further research is necessary to comprehensively understand their impact on symptoms and prognosis in the context of these KP alterations.

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“…41) prompt ed a fe\\ investigations on TRY metabolism in the serotonin and 5-hydroxyindolc-acetic acid (5-HIAA) path way (6,38). Subsequent studies on scleroderma were concerned mainly with the kynurenine-nia cin pathways of TRY metabolism (4,16,18,36).…”

mentioning

confidence: 99%

Intestinal absorption of L-tryptophan in scleroderma

Stachow¹,

Jabłońska²,

Skiendzielewska³

1976

Acta Derm Venereol

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The purpose of this investigation was to study the intestinal absorption of L-tryptophan and to assess the absorptive function of the intestine in scleroderma. The oral L-tryptophan loading test was performed in 31 cases of systemic scleroderma (progressive systemic sclerosis, PSS) and 3 cases of localized scleroderma. Serum levels of tryptophan and urinary excretion of indole-acetic acid (IAA) and indican (IS) were determined in order to assess intestinal absorption of tryptophan. In 10 cases the D-xylose test and in 4 cases Schilling's test was also performed. Furthermore, in vitro binding of L-tryptophan by plasma proteins in PSS and in other skin diseases as controls was studied. The normal increase in serum tryptophan after loading was noted in 17 cases (in 14 cases of PSS with a mild, slow progression in 3 cases of PSS with a severe, rapidly progressing course). In 10 of these cases, urinary excretion of IAA was higher than normal and in normal and in 3 cases excretion of urinary IS was also above normal. On the other hand, in 14 cases of severe, rapidly progressing PSS and in 2 of 3 cases of widespread linear scleroderma, serum levels of tryptophan were markedly depressed after loading, while urinary excretion of IAA and IS was normal. In all 4 cases studied, Schilling's test was normal, and only in 2 of 10 cases of PSS was the D-xylose test abnormal. It is concluded that in the majority of cases of PSS, intestinal absorpiton of tryptophan is normal as also is the absorptive function of the intestine. The slight rise in serum tryptophan after loading in some cases of PSS may be a result of increased binding of tryptophan by albumin.

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Tryptophan ? niacin pathway in scleroderma and in dermatomyositis

Cited by 14 publications

References 3 publications

Toward Understanding of Environmental Risk Factors in Systemic Sclerosis

Toward Understanding of Environmental Risk Factors in Systemic Sclerosis

Different Kynurenine Pathway Dysregulation in Systemic Sclerosis in Men and Women

Intestinal absorption of L-tryptophan in scleroderma

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