Carnosine is a natural dipeptide able to react with reactive carbonyl species, which have been recently associated with the onset and progression of several human diseases. Herein, we report an intervention study in overweight individuals. Carnosine (2 g/day) was orally administered for twelve weeks in order to evaluate its bioavailability and metabolic fate. Two carnosine adducts were detected in the urine samples of all subjects. Such adducts are generated from a reaction with acrolein, which is one of the most toxic and reactive compounds among reactive carbonyl species. However, neither carnosine nor adducts have been detected in plasma. Urinary excretion of adducts and carnosine showed a positive correlation although a high variability of individual response to carnosine supplementation was observed. Interestingly, treated subjects showed a significant decrease in the percentage of excreted adducts in reduced form, accompanied by a significant increase of the urinary excretion of both carnosine and carnosine-acrolein adducts. Altogether, data suggest that acrolein is entrapped in vivo by carnosine although the response to its supplementation is possibly influenced by individual diversities in terms of carnosine dietary intake, metabolism and basal production of reactive carbonyl species.

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BackgroundThe AGE-RAGE-oxidative stress (AROS) axis is involved in the onset and progression of metabolic syndrome induced by a high-fructose diet (HFD). PPARγ activation is known to modulate metabolic syndrome; however a systems-level investigation looking at the protective effects of PPARγ activation as related to the AROS axis has not been performed.The aim of this work is to simultaneously characterize multiple molecular parameters within the AROS axis, using samples taken from different body fluids and tissues of a rat model of HFD-induced metabolic syndrome, in the presence or absence of a PPARγ agonist, Rosiglitazone (RGZ).MethodsRats were fed with 60% HFD for the first half of the treatment duration (21 days) then continued with either HFD alone or HFD plus RGZ for the second half.ResultsRats receiving HFD alone showed metabolic syndrome manifestations including hypertension, dyslipidemia, increased glucose levels and insulin resistance, as well as abnormal kidney and inflammatory parameters. Systolic blood pressure, plasma triglyceride and glucose levels, plasma creatinine, and albuminuria were significantly improved in the presence of RGZ. The following molecular parameters of the AROS axis were significantly upregulated in our rat model: carboxymethyl lysine (CML) in urine and liver; carboxyethyl lysine (CEL) in urine; advanced glycation end products (AGEs) in plasma; receptor for advanced glycation end products (RAGE) in liver and kidney; advanced oxidation protein products (AOPP) in plasma; and 4-hydroxynonenal (HNE) in plasma, liver, and kidney. Conversely, with RGZ administration, the upregulation of AOPP and AGEs in plasma, CML and CEL in urine, RAGE in liver as well as HNE in plasma and liver was significantly counteracted/prevented.ConclusionsOur data demonstrate (i) the systems-level regulatory landscape of HFD-induced metabolic syndrome involving multiple molecular parameters, including HNE, AGEs and their receptor RAGE, and (ii) attenuation of metabolic syndrome by PPARγ modulation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12986-016-0149-z) contains supplementary material, which is available to authorized users.

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Herein, we reported a detailed profiling of soluble components of two fermented varieties of Chinese green tea, namely raw and ripe pu-erh. The identification and quantification of the main components was carried out by means of mass spectrometry and UV spectroscopy, after chromatographic separation. The antioxidant capacity towards different radical species, the anti-microbial and the enzyme inhibition activities of the extracts were then correlated to their main constituents. Despite a superimposable qualitative composition, a similar caffeine content, and similar enzyme inhibition and antimicrobial activities, raw pu-erh tea extract had a better antioxidant capacity owing to its higher polyphenol content. However, the activity of raw pu-erh tea seems not to justify its higher production costs and ripe variety appears to be a valid and low-cost alternative for the preparation of products with antioxidant or antimicrobial properties.

Endogenous lipid peroxidation (LPO)-derived aldehydes accumulate in human skin after photoexposure and contribute to the development of skin cytotoxicity and cancer. This study employed LC-ESI-MS and HPLC-UV-DAD techniques to investigate the effect of UVB radiation on the biotransformation and detoxification of the prototype aldehyde 4-hydroxy-2-trans-nonenal (HNE) using the human keratinocyte cell line (NCTC 2544). In parallel we followed the keratinocytes' cytotoxic response to HNE through morphological analysis and cell viability assay. In UVB-unstressed keratinocytes, even a supraphysiological dose of the aldehyde (200 microM) was rapidly and completely cleared in metabolized form (free and GSH-conjugated metabolites) from the cell, with no signs of cytotoxicity. By contrast, UVB preexposure already at 1 MED (50 mJ/cm2, the minimal erythemal dose in humans) markedly impaired HNE metabolism. After 2 h of incubation, the relative amount of GSH-conjugated adducts dose-dependently dropped from 44% (unirradiated cells) to 22% at 3 MED as a consequence of UVB-induced GSH depletion (no impairment of GST A4.4 nor of G6PD activities was observed). The levels of free metabolites, 1,4-dihydroxy-trans-nonene (DHN) and 4-hydroxy-trans-2-nonenoic acid (HNA), were modified (+30% DHN, -22% HNA) only at 3 MED, in parallel to the AR and ALDH enzyme activity modulation. In addition, a dose-dependent increase of unmodified HNE was found in the extracellular medium, paralleled by a significant fraction of the HNE-incubated dose not recovered at the intra- or extracellular level. The impairment of HNE metabolism paralleled a dramatic cytotoxic response. These results provide a reasonable explanation for the massive accumulation of carbonyl toxins in human skin in vivo after photoexposure and shed light on the detrimental effects of UVB radiation in the presence of unmetabolized LPO metabolites.

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