Activation of the eIF2α-ATF4 Pathway by Chronic Paracetamol Treatment Is Prevented by Dietary Supplementation with Cysteine.

Chronic treatment with acetaminophen (APAP) induces cysteine (Cys) and glutathione (GSH) deficiency which leads to adverse metabolic effects including muscle atrophy. Mammalian cells respond to essential amino acid deprivation through the phosphorylation of the eukaryotic translation initiation factor 2α (eIF2α). Phosphorylated eIF2α leads to the recruitment of activating transcription factor 4 (ATF4) to specific CCAAT/enhancer-binding protein-ATF response element (CARE) located in the promoters of target genes. Our purpose was to study the activation of the eIF2α-ATF4 pathway in response to APAP-induced Cys deficiency, as well as the potential contribution of the eIF2α kinase GCN2 and the effect of dietary supplementation with Cys. Our results showed that chronic treatment with APAP activated both GCN2 and PERK eIF2α kinases and downstream target genes in the liver. Activation of the eIF2α-ATF4 pathway in skeletal muscle was accompanied by muscle atrophy even in the absence of GCN2. The dietary supplementation with cysteine reversed APAP-induced decreases in plasma-free Cys, liver GSH, muscle mass, and muscle GSH. Our new findings demonstrate that dietary Cys supplementation also reversed the APAP-induced activation of GCN2 and PERK and downstream ATF4-target genes in the liver.

Effect of UVC pre-irradiation on the Suwannee river Natural Organic Matter (SRNOM) photooxidant properties.

The present study aimed to investigate the changes in the chemical composition, and in the optical and photooxidant properties of Suwannee River Natural Organic Matter (SRNOM) induced by UVC (254 nm) treatment. The extent of the photodegradation was first assessed by UV-visible/fluorescence spectroscopies and organic carbon analysis. An in-depth investigation of the chemical changes was also conducted using liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry after derivatizations. A series of mono, di and tricarbonyls and mono and dicarboxylic acids in C1C6 were identified in samples irradiated from 1 to 4 h. After 3 h of irradiation, carbonyls accounted for 46% of the organic carbon remaining in solution whereas carboxylic acids represented about 2%. Then, we investigated the modifications of the photooxidant properties of SRNOM induced by these chemical changes. At 254 nm, UVC pre-irradiated SRNOM photodegraded glyphosate 29 times faster than original SRNOM and the reaction was fully inhibited by 2-propanol (5 × 10-3 M). This enhanced photooxidant properties at 254 nm toward glyphosate was therefore reasonably due to •OH radicals formation, as confirmed by additional ESR measurements. A mechanism involving a chain reaction was proposed based on independent experiments conducted on carbonyl compounds, particularly pyruvic acid and acetone. The findings of this study show that UVC pre-treatment of NOM can enhance the removal of water pollutants and suggests a possible integration of a NOM pre-activation step in engineered water treatment sytems.

Innovative depollution treatment using multi-valent iron species: from fundamental study to application in municipal wastewater.

In this work, a new combination of oxidation treatments for the degradation of bisphenol A (BPA) is investigated. This innovative wastewater (WW) treatment includes the use of ferrate (FeO42-) and its decomposition byproducts under dark and UVA irradiation. The oxidation by ferrate leads to a fast but incomplete degradation of BPA with a degradation extent of 45% after 60 min under adopted experimental conditions. However, the ferrate decomposition byproducts which are constituted by solid iron species can be used to further improve the pollutant degradation efficiency. Indeed, ferrate-mediated heterogeneous photo-Fenton process is employed for the first time to enhance the degradation of BPA. With respect to the application for wastewater treatment, UVA irradiation (which is part of solar light), non-toxic and natural origin compounds such as ascorbic acid (AA) and ethylenediamine-N,N'-disuccinic acid (EDDS), are used to design a sustainable process. Under optimized conditions, the degradation extent of BPA using this newly designed treatment reaches almost 100% with AA and 70% with EDDS. In order to assess the feasibility of this treatment, the ferrate-mediated photo-Fenton process is applied to treat municipal wastewater. The obtained results in WW are highly encouraging since a maximum BPA degradation extent of 63% and 60% is observed after 300 min by using AA and EDDS, respectively.

Molecular Size Distribution of Fluorophores in Aquatic Natural Organic Matter: Application of HPSEC with Multi-Wavelength Absorption and Fluorescence Detection Following LPSEC-PAGE Fractionation.

Analytical high performance size exclusion liquid chromatography (HPSEC) with multiwavelength absorbance and fluorescence detections was used for the analysis of molecular size distribution and optical properties of dissolved natural organic matter. Experiments were conducted on Suwannee River organic matter (SRNOM) and its fractions A, B, C+D preliminary obtained by combination of preparative low pressure size exclusion chromatography and polyacrylamide gel electrophoresis (LPSEC-PAGE) and purified by dialysis on membrane with nominal cutoff 10 kDa, the fractions molecular size varied in order A > B > C + D > 10 kDa. The multistep fractionation of SRNOM enabled the size-separation of at least five types of humic-like fluorophores within NOM showing emission maxima at 465, 450, 435, 420, and 405 nm. The decrease of the humic-like emission maxima paralleled the decrease of the nominal molecular size of fluorescent SRNOM. The protein-like fluorescence was split into tyrosine-like and tryptophan-like fluorophores and only detected in fractions A and B. This work provides new data on the optical properties of size-fractionated NOM, which consistent with the formation of supramolecular NOM assemblies, likely controlled by association of low-molecular size components. It is clearly observed for the high molecular size fraction A, containing free amino acids or short peptides. The combination of several different fractionation procedures is very useful for obtaining less complex NOM compounds and understanding the NOM function in the environment.

Dietary supplementation with cysteine prevents adverse metabolic outcomes of repeated cures with paracetamol in old rats.

Cysteine (Cys), a conditionally indispensable amino acid, is required for the detoxification of paracetamol (acetaminophen, N-acetyl-para-aminophenol, 4-hydroxy-acetanilide, APAP), a drug of widespread use in older persons. We recently reported that repeated APAP cures could worsen sarcopenia in old rats, likely to be due to the impairment of Cys/GSH homoeostasis. The aim of the study was to evaluate whether a dietary Cys supplementation during APAP cures could improve Cys/GSH homoeostasis and thus preserve skeletal muscle. Male 21·5-month-old Wistar rats received three 2-week-long cures of APAP (1 % of diet) alone or with extra Cys (0·5 % of diet), intercalated with washout periods of 2 weeks (APAP and APAP-Cys groups, respectively). They were compared with untreated control rats (CT group). CT and APAP-Cys groups were pair-fed to the APAP group. Dietary Cys supplementation was efficient to prevent increase in liver mass (P<0·0001), decrease in liver GSH (P<0·0001), increase in blood GSH concentration (P<0·0001), and to some extent, decrease in plasma free Cys concentration (P<0·05), all induced by repeated APAP cures. The addition of Cys to APAP cures decreased plasma alanine transaminase (P<0·05), the fractional synthesis rate of liver proteins (P<0·01), and increased masses of extensor digitorum longus (P<0·01), and soleus (P<0·05), compared with the APAP group. Cys supplementation prevented alteration in Cys/GSH homoeostasis and increased some muscle masses in old rats under repeated cures with a non-toxic dose of APAP.

Improving the characterization of dissolved organic carbon in cloud water: Amino acids and their impact on the oxidant capacity.

Improving our understanding of cloud chemistry depends on achieving better chemical characterization (90% of the organic carbon [OC] fraction remains uncharacterized) and, consequently, assessing the reactivity of this complex system. In this manuscript, we report for the first time the concentrations of 16 amino acids (AAs) in 25 cloud water samples. The concentrations of individual AAs ranged from a few nM up to ~2.0 µM, and the average contribution of AAs corresponded to 9.1% (4.4 to 21.6%) of the dissolved OC (DOC) concentration. Considering their occurrence and concentrations, AAs were expected to represent an important hydroxyl radical (HO•) sink in aqueous cloud samples. In this work, we estimated that approximately 17% (from 7 to 36%) of the hydroxyl radical-scavenging ability of the DOC could be attributed to the presence of AAs, whereas comparing the AAs suggested that an average of 51% (from 22 to 80%) of their reactivity with HO• could account for the presence of tryptophan. These results clearly demonstrate that the occurrence and reactivity of AAs must be considered to better estimate the chemical composition and oxidant capacity of the cloud aqueous phase.

Phototransformation of azoxystrobin fungicide in organic solvents. Photoisomerization vs. photodegradation.

Azoxystrobin is a systemic fungicide that has a tendency to accumulate at the surface of crop leaves or inside their cuticle where it undergoes photodegradation. Its photochemistry was investigated in n-heptane and isopropanol to mimic the polarity of wax leaves. Using analytical and kinetic data, we demonstrate that azoxystrobin (isomer E) undergoes efficient photoisomerization into the isomer Z with a quantum yield of 0.75 ± 0.08. This value is 30-fold higher than that reported in aqueous solution. The photoisomerization of isomer Z into azoxystrobin is more efficient with a chemical yield of 0.95 ± 0.1. In addition, a pseudo photostationary equilibrium is reached when the ratio [azoxystrobin]/[isomer Z] is 2.0 ± 0.1. Photodegradation also takes place from azoxystrobin (quantum yield = 0.073 ± 0.008). Photoproducts mainly arise from bond cleavage between rings and from demethylation of the ether with or without saturation of the acrylate double bond. Theoretical calculations were undertaken to investigate the photoisomerization mechanism and the solvent effect. These data show that the photochemical reactivity of azoxystrobin is enhanced when the solvent polarity decreases and thus should be significant in leaf waxes.

Analysis of electrophoretic soil humic acids fractions by reversed-phase high performance liquid chromatography with on-line absorbance and fluorescence detection.

A combination of reversed-phase high performance liquid chromatography (RP HPLC) with on-line absorbance and fluorescence detection was used for analysis of chernozem soil humic acids (HAs) and their fractions A, B and C+D with different electrophoretic mobility (EM) and molecular size (MS). Samples were injected onto the column at the identical volume and absorbance. All chromatograms exhibit the resolution of seven peaks. The estimation of relative recovery of HAs and fractions from the reverse-phase column has been done. High MS fraction A, which possesses the low EM, is essentially more hydrophobic (73% of the fraction amount remained adsorbed on the column) and aliphatic than medium MS and EM fraction B (33% of the fraction amount remained adsorbed on the column). The most hydrophilic and aromatic properties belong to low MS fraction C+D, which possess the highest EM and practically was not adsorbed on the column. The hydrophobicity of the bulk HAs lies within the range of fractions hydrophobicity. The absorption spectra of bulk HAs, electrophoretic fractions A, B, C+D and corresponding RP HPLC peaks were featureless but had differences in the values of absorbance ratio at 300 and 400 nm (A3/A4). For fractions A and B this ratio gradually decreased from peak 1 to 7 (from 3.05 to 2.80 and 3.00 to 2.40, respectively). This trend was less pronounced in HAs and practically absent in fraction C+D, where ratio A3/A4 varied within a small range. The strong relationship between fluorescence properties, EM, MS, polarity and aliphaticity/aromaticity of HAs fractions was found. Humic and protein-like fluorescence had different polarity nature. The protein-like fluorescence is located in humic material which irreversibly adsorbed on the reverse-phase column and not subjected to RP HPLC characterization. The humic-like fluorescence at Ex/Em 270/450 nm is mostly located in the hydrophilic peak of low MS fraction C+D. Taking into account that high MS fraction A consisted mainly of aliphatic components it is reasonable to suggest that these associations are capable of organizing into micellar structures. These data could be of great environmental importance, because the different fractions might reflect different soil physical-chemical properties.