Indolelactic acid

Alteration of Metabolic Profile and Potential Biomarkers in the Plasma of Alzheimer's Disease.[Pubmed:33269100]

Aging Dis. 2020 Dec 1;11(6):1459-1470.

The expending of elderly population worldwide has resulted in a dramatic rise in the incidence of chronic diseases such as Alzheimer's disease (AD). Inadequate understanding of the mechanisms underlying AD has hampered the development of efficient tools for definitive diagnosis and curative interventions. Previous studies have attempted to discover reliable biomarkers of AD, but these biomarkers can only be measured through invasive (neuropathological markers in cerebrospinal fluid) or expensive (positron emission tomography scanning or magnetic resonance imaging) techniques. Metabolomics is a high-throughput technology that can detect and catalog large numbers of small metabolites and may be a useful tool for characterization of AD and identification of biomarkers. In this study, we used ultra-performance liquid chromatography-mass spectrometry based untargeted metabolomics to measure the concentrations of plasma metabolites in a cohort of subjects with AD (n=44) and cognitively normal controls (Ctrl, n=94). The AD group showed marked reductions in levels of polyunsaturated fatty acids, acyl-carnitines, degradation products of tryptophan, and elevated levels of bile acids compared to the Ctrl group. We then validated the results using an independent cohort that included subjects with AD (n=30), mild cognitive impairment (MCI, n=13), healthy controls (n=43), and non-AD neurological disease controls (NDC, n=31). We identified five metabolites comprising cholic acid, chenodeoxycholic acid, allocholic acid, Indolelactic acid, and tryptophan that were able to distinguish patients with AD from both Ctrl and NDC with satisfactory sensitivity and specificity. The concentrations of these metabolites were significantly correlated with disease severity. Our results also suggested that altered bile acid profiles in AD and MCI might indicate early risk for the development of AD. These findings may allow for development of new approaches for diagnosis of AD and may provide novel insights into AD pathogenesis.

Plasma Metabolomics Profiling in Maintenance Hemodialysis Patients Based on Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry.[Pubmed:32309295]

Kidney Dis (Basel). 2020 Mar;6(2):125-134.

Background: Key pathogenetic mechanisms underlying renal disease progression are unaffected by current treatment. Metabolite profiling has significantly contributed to a deeper understanding of the biochemical metabolic networks and pathways in disease, but the biochemical details in maintenance hemodialysis (MHD) patients remain largely undefined. Methods: The metabolic fingerprinting of plasma samples from 19 MHD patients and 12 healthy controls was characterized using liquid chromatography quadrupole time-of-flight mass spectrometry. Principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were applied to analyze the metabolic data. Results: The plasma metabolite profile distinguished the MHD patients from the healthy controls successfully by using both PCA and OPLS-DA models. Sixty-three metabolites were identified as the key metabolites to discriminate the MHD patients from healthy controls, involving several metabolic pathways (all p < 0.05). An increase in plasma levels of D-glucose, hippuric acid, androsterone glucuronide, Indolelactic acid, and a reduction in plasma levels of glycerophosphocholine, serotonin, L-lactic acid, phytosphingosine, and several lysophosphatidylcholine were observed in MHD patients compared to healthy subjects. Metabolomics analysis combined with KEGG pathway enrichment analysis revealed that non-alcoholic fatty liver disease, choline metabolism in cancer, the forkhead box O signaling pathway, and the hypoxia-inducible factor-1 signaling pathway in MHD patients were significantly changed (p < 0.05). Conclusion: The identification of a novel signaling pathway and key metabolite markers in MHD patients provides insights into potential pathogenesis and valuable pharmacological targets for end-stage renal disease.

Mechanistic evaluation of gastro-protective effects of KangFuXinYe on indomethacin-induced gastric damage in rats.[Pubmed:31955823]

Chin J Nat Med. 2020 Jan;18(1):47-56.

KangFuXinYe (KFX), the ethanol extract of the dried whole body of Periplaneta americana, is a well-known important Chinese medicine preparation that has been used to treat digestive diseases such as gastric ulcers for many years in China. However, its therapeutic effect and mechanism are not yet well understood. Thus, the aim of this study was to investigate the gastro-protective effects of KangFuXinYe (KFX) in indomethacin-induced gastric damage. Rats were randomly divided into six groups as follows: control, treated with indomethacin (35 mg.kg(-1)), different dosages of KFX (2.57, 5.14 and 10.28 mL.kg(-1), respectively) plus indomethacin, and sucralfate (1.71 mL.kg(-1)) plus indomethacin. After treatment, rat serum, stomach and gastric homogenates were collected for biochemical tests and examination of histopathology firstly. Rat serum was further used for metabolomics analysis to research possible mechanisms. Our results showed that KFX treatment alleviated indomethacin-induced histopathologic damage in rat gastric mucosa. Meanwhile, its treatment significantly increased cyclooxygenase-1 (COX-1), prostaglandin E2 (PGE2) and epidermal growth factor (EGF) levels in rat serum and gastric mucosa. Moreover, KFX decreased cyclooxygenase-2 (COX-2) and interleukin-6 (IL-6) levels. Nine metabolites were identified which intensities significantly changed in gastric damage rats, including 5-hydroxyindoleacetic acid, indoxylsulfuric acid, Indolelactic acid, 4-hydroxyindole, pantothenic acid, isobutyryl carnitine, 3-methyl-2-oxovaleric acid, sphingosine 1-phosphate, and indometacin. These metabolic deviations came to closer to normal levels after KFX intervention. The results indicate that KFX (10.28 mL.kg(-1)) exerts protective effects on indomethacin-induced gastric damage by possible mechanisms of action (regulating tryptophan metabolism, protecting the mitochondria, and adjusting lipid metabolism, and reducing excessive indomethacin).

Plasma metabolomics analysis of endogenous and exogenous metabolites in the rat after administration of Lonicerae Japonicae Flos.[Pubmed:31813160]

Biomed Chromatogr. 2020 Mar;34(3):e4773.

Lonicerae Japonicae Flos (LJF) is a typical herbal medicine and is used as a functional food. LJF, which has complex chemical compounds, has various biological effects. The global metabolomics, focusing on both the endogenous and exogenous metabolites, have not yet been investigated for LJF in normal healthy rats using LC-MS. In this study, plasma metabolomics was analyzed after the administration of LJF at different time intervals, and the exogenous metabolites were identified. Partial least squares discriminant analysis showed significant differences in chemical content in the dosed rats. Cholic acid, indoleacrylic acid, Indolelactic acid, hippuric acid, N-acetyl-phenylalanine, and N-acetyl-serotonin significantly accumulated in the dosed rats. Lysophosphatidylethanolamine and lysophosphatidylcholine content, including plasmalogen, increased. There were 25 components of LJF, including 15 prototypes and 10 metabolites, that were identified. The 15 prototypes included phenolic acids, flavonoids, and iridoids, and their contents decreased with an increase in the administration time. Glucuronidation and sulfation of polyphenols were found for LJF. The exogenous glucuronide and sulfate metabolites-including dihydrocoumaric acid-sulfate, dihydrocaffeic acid-sulfate, dihydroferulic acid-sulfate, apigenin-glucuronide, apigenin-glucuronide-sulfate, isorhamnetin-glucuronide-sulfate, and others-were identified with a neutral loss of 176 and 80, respectively. The metabolic differences found in the study may serve as biomarkers of LJF consumption and promote the understanding of the mechanism of action of LJF.

Nocturnal Gamma-Hydroxybutyrate Reduces Cortisol-Awakening Response and Morning Kynurenine Pathway Metabolites in Healthy Volunteers.[Pubmed:31504554]

Int J Neuropsychopharmacol. 2019 Oct 1;22(10):631-639.

BACKGROUND: Gamma-hydroxybutyrate (GHB; or sodium oxybate) is an endogenous GHB-/gamma-aminobutyric acid B receptor agonist. It is approved for application in narcolepsy and has been proposed for the potential treatment of Alzheimer's disease, Parkinson's disease, fibromyalgia, and depression, all of which involve neuro-immunological processes. Tryptophan catabolites (TRYCATs), the cortisol-awakening response (CAR), and brain-derived neurotrophic factor (BDNF) have been suggested as peripheral biomarkers of neuropsychiatric disorders. GHB has been shown to induce a delayed reduction of T helper and natural killer cell counts and alter basal cortisol levels, but GHB's effects on TRYCATs, CAR, and BDNF are unknown. METHODS: Therefore, TRYCAT and BDNF serum levels, as well as CAR and the affective state (Positive and Negative Affect Schedule [PANAS]) were measured in the morning after a single nocturnal dose of GHB (50 mg/kg body weight) in 20 healthy male volunteers in a placebo-controlled, balanced, randomized, double-blind, cross-over design. RESULTS: In the morning after nocturnal GHB administration, the TRYCATs Indolelactic acid, kynurenine, kynurenic acid, 3-hydroxykynurenine, and quinolinic acid; the 3-hydroxykynurenine to kynurenic acid ratio; and the CAR were significantly reduced (P < 0.05-0.001, Benjamini-Hochberg corrected). The quinolinic acid to kynurenic acid ratio was reduced by trend. Serotonin, tryptophan, and BDNF levels, as well as PANAS scores in the morning, remained unchanged after a nocturnal GHB challenge. CONCLUSIONS: GHB has post-acute effects on peripheral biomarkers of neuropsychiatric disorders, which might be a model to explain some of its therapeutic effects in disorders involving neuro-immunological pathologies. This study was registered at ClinicalTrials.gov as NCT02342366.

A prospective pilot study using metabolomics discloses specific fatty acid, catecholamine and tryptophan metabolic pathways as possible predictors for a negative outcome after severe trauma.[Pubmed:31118076]

Scand J Trauma Resusc Emerg Med. 2019 May 22;27(1):56.

BACKGROUND: We wanted to define metabolomic patterns in plasma to predict a negative outcome in severe trauma patients. METHODS: A prospective pilot study was designed to evaluate plasma metabolomic patterns, established by liquid chromatography coupled to mass spectrometry, in patients allocated to an intensive care unit (in the University Hospital Arnau de Vilanova, Lleida, Spain) in the first hours after a severe trauma (n = 48). Univariate and multivariate statistics were employed to establish potential predictors of mortality. RESULTS: Plasma of patients non surviving to trauma (n = 5) exhibited a discriminating metabolomic pattern, involving basically metabolites belonging to fatty acid and catecholamine synthesis as well as tryptophan degradation pathways. Thus, concentration of several metabolites exhibited an area under the receiver operating curve (ROC) higher than 0.84, including 3-Indolelactic acid, hydroxyisovaleric acid, phenylethanolamine, cortisol, epinephrine and myristic acid. Multivariate binary regression logistic revealed that patients with higher myristic acid concentrations had a non-survival odds ratio of 2.1 (CI 95% 1.1-3.9). CONCLUSIONS: Specific fatty acids, catecholamine synthesis and tryptophan degradation pathways could be implicated in a negative outcome after trauma. The metabolomic study of severe trauma patients could be helpful for biomarker proposal.

Biomarkers of Individual Foods, and Separation of Diets Using Untargeted LC-MS-based Plasma Metabolomics in a Randomized Controlled Trial.[Pubmed:30094970]

Mol Nutr Food Res. 2019 Jan;63(1):e1800215.

SCOPE: Self-reported dietary intake does not represent an objective unbiased assessment. The effect of the new Nordic diet (NND) versus average Danish diet (ADD) on plasma metabolic profiles is investigated to identify biomarkers of compliance and metabolic effects. METHODS AND RESULTS: In a 26-week controlled dietary intervention study, 146 subjects followed either NND, a predominantly organic diet high in fruit, vegetables, whole grains, and fish, or ADD, a diet higher in imported and processed foods. Fasting plasma samples are analyzed with untargeted ultra-performance liquid chromatography-quadruple time-of-flight. It is demonstrated that supervised machine learning with feature selection can separate NND and ADD samples with an average test set performance of up to 0.88 area under the curve. The NND plasma metabolome is characterized by diet-related metabolites, such as pipecolic acid betaine (whole grain), trimethylamine oxide, and prolyl hydroxyproline (both fish intake), while theobromine (chocolate) and proline betaine (citrus) were associated with ADD. Amino acid (i.e., Indolelactic acid and hydroxy-3-methylbutyrate) and fat metabolism (butyryl carnitine) characterize ADD whereas NND is associated with higher concentrations of polyunsaturated phosphatidylcholines. CONCLUSIONS: The plasma metabolite profiles are predictive of dietary patterns and reflected good compliance while indicating effects of potential health benefit, including changes in fat metabolism and glucose utilization.

Multiplatform plasma fingerprinting in cancer cachexia: a pilot observational and translational study.[Pubmed:29464940]

J Cachexia Sarcopenia Muscle. 2018 Apr;9(2):348-357.

BACKGROUND: Cachexia is a metabolic syndrome that affects up to 50-80% of cancer patients. The pathophysiology is characterized by a variable combination of reduced food intake and abnormal metabolism, including systemic inflammation and negative protein and energy balance. Despite its high clinical significance, defined diagnostic criteria and established therapeutic strategies are lacking. The 'omics' technologies provide a global view of biological systems. We hypothesize that blood-based metabolomics might identify findings in cachectic patients that could provide clues to gain knowledge on its pathophysiology, and eventually postulate new therapeutic strategies. METHODS: This is a cross-sectional observational study in two cohorts of cancer patients, with and without cachexia. Patients were consecutively recruited from routine clinical practice of a General Oncology Department at '12 de Octubre' University Hospital. Selected clinical and biochemical features were collected. Blood metabolite fingerprinting was performed using three analytical platforms, gas chromatography coupled to mass spectrometry (GC-MS), capillary electrophoresis coupled to mass spectrometry (CE-MS), and liquid chromatography coupled to mass spectrometry (LC-MS). Besides, we performed pathway-based metabolite analyses to obtain more information on biological functions. RESULTS: A total of 15 subjects were included in this study, 8 cachectic and 7 non-cachectic patients. Metabolomic analyses were able to correctly classify their samples in 80% (GC-MS), 97% (CE-MS), 96% [LC-MS (positive mode)], and 89% [LC-MS (negative mode)] of the cases. The most prominent metabolic alteration in plasma of cachectic patients was the decrease of amino acids and derivatives [especially arginine, tryptophan, Indolelactic acid, and threonine, with 0.4-fold change (FC) compared with non-cachectic patients], along with the reduction of glycerophospholipids [mainly lysophosphatidylcholines(O-16:0) and lysophosphatidylcholines(20:3) sn-1, FC = 0.1] and sphingolipids [SM(d30:0), FC = 0.5]. The metabolite with the highest increase was cortisol (FC = 1.6). Such alterations suggest a role of the following metabolic pathways in the pathophysiology of cancer cachexia: arginine and proline metabolism; alanine, aspartate, and glutamate metabolism; phenylalanine metabolism; lysine degradation; aminoacyl-tRNA biosynthesis; fatty acid elongation in mitochondria; tricarboxylic acids cycle; among others. CONCLUSIONS: These findings suggest that plasma amino acids and lipids profiling has great potential to find the mechanisms involved in the pathogenesis of cachexia. Metabolic profiling of plasma from cancer patients show differences between cachexia and non-cachexia in amino acids and lipids that might be related to mechanisms involved in its pathophysiology. A better understanding of these mechanisms might identify novel therapeutic approaches to palliate this unmet medical condition.

Cord Blood Metabolic Signatures of Birth Weight: A Population-Based Study.[Pubmed:29401400]

J Proteome Res. 2018 Mar 2;17(3):1235-1247.

Birth weight is an important indicator of maternal and fetal health and a predictor of health in later life. However, the determinants of variance in birth weight are still poorly understood. We aimed to identify the biological pathways, which may be perturbed by environmental exposures, that are important in determining birth weight. We applied untargeted mass-spectrometry-based metabolomics to 481 cord blood samples collected at delivery in four birth cohorts from across Europe: ENVIRONAGE (Belgium), INMA (Spain), Piccolipiu (Italy), and Rhea (Greece). We performed a metabolome-wide association scan for birth weight on over 4000 metabolic features, controlling the false discovery rate at 5%. Annotation of compounds was conducted through reference to authentic standards. We identified 68 metabolites significantly associated with birth weight, including vitamin A, progesterone, docosahexaenoic acid, Indolelactic acid, and multiple acylcarnitines and phosphatidylcholines. We observed enrichment (p < 0.05) of the tryptophan metabolism, prostaglandin formation, C21-steroid hormone signaling, carnitine shuttle, and glycerophospholipid metabolism pathways. Vitamin A was associated with both maternal smoking and birth weight, suggesting a mediation pathway. Our findings shed new light on the pathways central to fetal growth and will have implications for antenatal and perinatal care and potentially for health in later life.

Magnolol, a Natural Polyphenol, Attenuates Dextran Sulfate Sodium-Induced Colitis in Mice.[Pubmed:28726741]

Molecules. 2017 Jul 20;22(7). pii: molecules22071218.

Magnolol is a lignan with anti-inflammatory activity identified in Magnolia officinalis. Ulcerative colitis (UC), one of the types of inflammatory bowel disease (IBD), is a disease that causes inflammation and ulcers in the colon. To investigate the effect of magnolol in dextran sulfate sodium (DSS)-induced experimental UC model, male C57 mice were treated with 2% DSS drinking water for 5 consecutive days followed by intragastric administration with magnolol (5, 10 and 15 mg/kg) daily for 7 days. The results showed that magnolol significantly attenuated disease activity index, inhibited colonic shortening, reduced colonic lesions and suppressed myeloperoxidase (MPO) activity. Moreover, colonic pro-inflammatory cytokines (TNF-alpha, IL-6, and IL-1beta) induced by colitis were dramatically decreased by magnolol. To further unveil the metabolic signatures upon magnolol treatment, mass spectrometry-based metabolomic analysis of the small molecular metabolites in mice serum were performed. Compared with controls, abnormality of serum metabolic phenotypes in DSS-treated mice were effectively reversed by different doses of magnolol. In particular, magnolol treatment effectively elevated the serum levels of tryptophan metabolites including kynurenic acid (KA), 5-hydroxyindoleacetic acid, indoleacetic acid (IAA), Indolelactic acid and indoxylsulfuric acid, which are potential aryl hydrocarbon receptor (AHR) ligands to impact colitis. These findings suggest that magnolol exerts anti-inflammatory effect on DSS-induced colitis and its underlying mechanisms are associated with the restoring of tryptophan metabolites that inhibit the colonic inflammation.

Identification of potential biomarkers for ovarian cancer by urinary metabolomic profiling.[Pubmed:23163809]

J Proteome Res. 2013 Jan 4;12(1):505-12.

To evaluate the application of urinary metabolomics on discovering potential biomarkers for epithelial ovarian cancer (EOC), urine samples from 40 preoperative EOC patients, 62 benign ovarian tumor (BOT) patients, and 54 healthy controls were collected and analyzed with ultraperformance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS). Good separations were obtained for EOC vs BOT, EOC vs healthy controls analyzed by partial least-squares discriminant analysis, or principal component analysis. Twenty-two ascertained metabolomic biomarkers were found to be disturbed in several metabolic pathways among EOC patients, including nucleotide metabolism (pseudouridine, N4-acetylcytidine), histidine metabolism (L-histidine, imidazol-5-yl-pyruvate), tryptophan metabolism (3-Indolelactic acid), and mucin metabolism (3'-sialyllactose and 3-sialyl-N-acetyllactosamine). In addition, the concentrations of some urinary metabolites of 18 postoperative EOC patients among the 40 EOC patients changed significantly compared with those of their preoperative condition, and four of them suggested recovery tendency toward normal level after surgical operation, including N4-acetylcytidine, pseudouridine, urate-3-ribonucleoside, and succinic acid. These metabolites would be highly postulated to be associated with EOC. In conclusion, our study demonstrated that urinary metabolomics analysis by UPLC-QTOF/MS, performed in a minimally noninvasive and convenient manner, possessed great potential in biomarker discovery for EOC.

Metabonomics biomarkers for subacute toxicity screening for benzene exposure in mice.[Pubmed:22891888]

J Toxicol Environ Health A. 2012;75(18):1163-73.

Benzene is known to produce hematotoxicity in occupational exposure workers. This study examined the utility of metabonomic biomarkers to ascertain subacute toxicity produced by benzene in male C3H/He mice. A 30-d intermittent collection of urine was obtained from mice in this experiment. The relative organ weights, blood parameters, and bone marrow smears were examined to identify specific changes of benzene-induced toxicity. In addition, an integrated analytical approach based on liquid chromatography coupled with mass spectrometry (LC-MS) was developed to map metabolic responses in urine. Five endogenous metabolites, hypoxanthine, spermidine, 4-aminohippuric acid, Indolelactic acid, and glutamylphenylalanine, were identified as potential biomarkers of benzene-induced toxicity, indicating that pathways of purine, spermidine, fatty acid, tryptophan, and peptides metabolism might be disturbed in benzene-exposed mice. Our findings showed that the use of urine metabonomics was a more sensitive tool to detect benzene-induced toxicity compared to body weight or blood parameter changes.

Lactic acid bacteria community dynamics and metabolite production of rye sourdough fermentations share characteristics of wheat and spelt sourdough fermentations.[Pubmed:20832677]

Food Microbiol. 2010 Dec;27(8):1000-8.

Four spontaneous rye sourdough fermentations were performed over a period of ten days with daily back-slopping. Samples taken at all refreshment steps were used for culture-dependent and culture-independent characterization of the microbiota present. Furthermore, an extensive metabolite target analysis was performed through a combination of various chromatographic methods, including liquid chromatography coupled to mass spectrometry (LC/MS) and gas chromatography coupled to mass spectrometry (GC/MS). Spearman's rank correlation coefficients were calculated and a principal component analysis (PCA) was performed on the data obtained in this study combined with data obtained previously for wheat and spelt sourdoughs. In general, the establishment of a stable microbial ecosystem occurred through a three-phase evolution, with mainly Lactobacillus plantarum and Lactobacillus fermentum dominating the rye sourdough ecosystems. PCA revealed that ornithine and mannitol were positively correlated with rye sourdoughs, contributing to bacterial competitiveness at the onset of sourdough production. Wheat and spelt sourdoughs showed a high degree of similarity, although certain compounds (e.g. Indolelactic acid) appeared to be specific for spelt sourdoughs. The production of amino acid metabolites, mainly hydroxy acids (e.g. phenyllactic acid) and alcohols (e.g. 3-methyl-1-butanol), contributed to the equilibration of the redox balance and further enhanced the competitiveness of dominant species in stable sourdoughs.

Enantioselective oxidation of 2-hydroxy carboxylic acids by glycolate oxidase and catalase coexpressed in methylotrophic Pichia pastoris.[Pubmed:20014430]

Biotechnol Prog. 2010 May-Jun;26(3):607-15.

Glycolate oxidase (GO; (S)-2-hydroxyacid oxidase, EC 1.1.3.15) is a flavin mononucleotide (FMN)-dependent enzyme, which catalyzes the oxidation of 2-hydroxy carboxylic acids to the corresponding 2-keto acids. Catalase has been used as cocatalyst to decompose hydrogen peroxide produced in the reaction, thus limiting peroxide-based side reactions and GO deactivation. GO from spinach and catalase T from Saccharomyces cerevisiae previously coexpressed in Pichia pastoris strain NRRL Y-21001, was permeabilized and used for the oxidation of 3-phenyllactic acid, 3-Indolelactic acid, 3-chlorolactic acid, 2-hydroxybutanoic acid, and 2-hydroxydecanoic acid to demonstrate high degree of selectivity to the (S)-enantiomers, leaving (R)-isomers intact. The rates of oxidation ranged from 1.3 to 120.0%, relative to the oxidation of lactic acid to pyruvic acid. The best substrates were 3-chlorolactic acid (110%) and 2-hydroxybutanoic acid (120%). Oxidation was carried out with (R)-, (S)-, and (RS)-3-phenyllactic acid, (RS)-lactic acid, and (RS)-2-hydroxybutanoic acid in 500 mL scale to characterize the products and stoichiometry of the reaction. All (RS)- and (S)-2-hydroxy acids produced 2-keto acids at close to the theoretical yield in 1-9 h. (R)-3-Phenyllactic acid was not oxidized over a period of 9 h. Addition of exogenous FMN and catalase were not required for this oxidation using double recombinant Pichia pastoris whole cells. As GO is absolutely specific to (S)-enantiomers, it can be used for resolution of racemic 2-hydroxy acids to (R)-2-hydroxy acids as well as for production of 2-keto acids. This is the first report on the selectivity of a broad range of 2-hydroxy acids by GO.

Isolation and cytotoxicity of low-molecular-weight metabolites of Candida albicans.[Pubmed:18508703]

Front Biosci. 2008 May 1;13:6893-904.

In this study, the low molecular weight lypophilic metabolites of C. albicans and C. dubliniensis strains produced in a synthetic medium with the addition of fetal calf serum were identified using LC/MS and MS/MS technique and quantified. All strains investigated produce a metabolite with a UV spectra maximum at 224 and 279 nm and minimum at 243 nm. Following comparison with ESI, MS/MS spectral data of a reference compound, the metabolite was identified as 3-indoleethanol (tryptophol). The concentration of extracellular tryptophol in the biosynthesis of C. albicans and C. dubliniensis ranged from 2.45 microg/mL to 191 microg/mL, respectively. Contrary to previously published data, gliotoxin or gliotoxin-like compounds were not detected, and all investigated C. albicans and C. dubliniensis strains have the same metabolite profile. Cytotoxic effects of tryptophol and 3-Indolelactic acid (precursor of tryptophol biosynthesis) were cell-line-dependent. The EC50 of tryptophol ranged between 2 and 7 mM, with the EC50 of 3-Indolelactic acid approximately double (between 4 and 8 mM). Tryptophol exhibited cell-type dependent cytotoxicity in relatively high concentrations, with domination of apoptosis.