•Most antioxidant phenolics exhibit anti-proliferative activity in cancer cells.•Extracts with higher phenolic content usually exhibit higher cytotoxic activity.•The correlation between antioxidant ...and cytotoxic activities is not always clear.•Brain, larynx, ovarian, pancreas, pleura and retina cancer cells are few studied.•Few studies of structure-anticancer activity relationships on phenolics are reported.
In this paper, a review of the literature on the phenolic compounds with anticancer activity published between 2008 and 2012 is presented. In this overview only phenolic antioxidant compounds that display significant anticancer activity have been described. In the first part of this review, the oxidative and nitrosative stress relation with cancer are described. In the second part, the plant-derived food extracts, containing identified phenolic antioxidants, the phenolic antioxidants isolated from plants and plant-derived food or commercially available and the synthetic ones, along with the type of cancer and cells where they exert anticancer activity, are described and summarized in tables. The principal mechanisms for their anti-proliferative effects were also described. Finally, a critical analysis of the studies and directions for future research are included in the conclusion.
•Excessive addition or improper use of SPAs can produce possible harms.•BHT can induce apoptosis and promote tumorigenesis.•BHA metabolites are involved in carcinogenicity process.•TBHQ ...carcinogenicity is related to induction of TQ and CYP1A1.
Synthetic phenolic antioxidants can interact with peroxides produced by food. This paper reviews correlation between BHA, BHT and TBHQ metabolism and harms they cause and provides a theoretical basis for rational use of BHA, BHT and TBHQ in food, and also put some attention on the transformation and metabolic products of PG. We introduce BHA, BHT, TBHQ, PG and their possible metabolic pathways, and discuss possible harms and their specific mechanisms responsible. Excessive addition or incorrect use of synthetic phenolic antioxidants results in carcinogenicity, cytotoxicity, oxidative stress induction and endocrine disrupting effects, which warrant attention. BHA carcinogenicity is related to production of metabolites TBHQ and TQ, and cytotoxic effect of BHA is the main cause of apoptosis induction. BHT carcinogenicity depends on DNA damage degree, and tumour promotion is mainly related to production of quinone methylation metabolites. TBHQ carcinogenicity is related to induction of metabolite TQ and enzyme CYP1A1.
The continuous improvement of living standards is related to higher requirements for the freshness and taste of food. For example, synthetic phenolic antioxidants (SPAs) are added to fats and fried ...foods as food additives to minimize the oxidative rancidity of oils and fats. Hence, the global use of SPAs is increasing year by year. Dibutyl hydroxytoluene is one of the widely used SPAs, often in combination with butyl hydroxyanisole or gallate SPAs. The extensive use of these compounds makes them and their transformation products to be widespread in various environmental matrices, including indoor dust, wastewater, river water, sewage sludge, and sediment, as well as human samples, such as nails and urine, at concentrations varying from nanogram per gram (ng/g) to microgram per gram (μg/g). Animal experiments have shown that high-dose SPA exposure is toxic, which may lead to DNA damage and mismatches and the development of cancerous tumors. Since the biosphere shares the same set of genetic codes, humans and animals have many identical or similar feedback mechanisms and information pathways. Therefore, the damage of SPAs to animals may also threaten human health. This review discusses the properties, occurrence, analysis, and environmental health risks of typical SPAs, including butyl hydroxyanisole, dibutyl hydroxytoluene, tert-butylhydroquinone, propyl gallate, octyl gallate, and lauryl gallate, used as food additives. In addition, AO2246, which is used in food packaging bags, is also considered. Future research directions on SPAs and their transformation products (TPs) are identified and discussed.
Display omitted
•Analytical methods of SPAs and TPs based on GC and HPLC were summarized.•BHA, and BHT and its TPs are frequently detected in various environmental matrices.•Human exposure to SPAs is minor compared with the ADIs.•The lack of PNECs may cause inaccurate risk assessment of SPAs.
•SPAs were measured in indoor dust collected from 10 provinces in China.•The concentrations of ∑6SPAs in indoor dust were 15.4 to 3210 ng/g dry weight.•The highest concentration of ∑6SPAs was found ...in Sichuan Province.•Toddlers have the highest risk of exposure to SPAs from dust.
Synthetic phenolic antioxidants (SPAs) are widely used in diverse industries due to their exceptional antioxidant characteristics. However, human exposure to SPAs may cause health problems. In this study, 226 dust samples were collected from 10 provinces in China, and six SPAs (three parent SPAs and their three transformation products) were analyzed. The concentrations of ∑6SPAs (the sum of six target compounds) ranged from 15.4 to 3210 ng/g (geometric mean (GM): 169 ng/g). The highest concentration of ∑6SPAs was found in Sichuan Province (GM: 349 ng/g), which was approximately 4 times higher than that in Hubei Province (81.6 ng/g) (p < 0.05). The concentrations of butylated hydroxytoluene (BHT), 2,2′-methylene bis (4-methyl-6‑tert-butylphenol) (AO2246), 2,6-di‑tert‑butyl‑1,4-benzoquinone (BHT-Q), 2,6-di‑tert‑butyl‑4-(hydroxymethyl) phenol (BHT-OH), and ∑p-SPAs were substantially higher in dust from urban areas than rural areas (p < 0.05). AO2246 concentration in dust from homes (GM: 0.400 ng/g) was about 4 times higher than that in workplaces (0.116 ng/g) (p < 0.01). Significantly higher ∑p-SPAs concentrations were found in dust from homes (GM: 17.5 ng/g) than workplaces (11.4 ng/g) (p < 0.01). The estimated daily intakes (EDIs) of ∑6SPAs exposed through dust ingestion were 0.582, 0.342, 0.197, 0.076, and 0.080 ng/kg bw/day in different age groups, and exposed through dermal contact was 0.358, 0.252, 0.174, 0.167, and 0.177 ng/kg bw/day. EDIs showed that the exposure risks of SPAs decreased with age. This is the first work to determine SPAs in dust from 10 provinces in China and investigate the spatial distribution of SPAs in those regions.
Display omitted
Synthetic phenolic antioxidants (SPAs) have received increasing attention due to the reports of toxicity and environmental contamination. Nevertheless, limited information was available on human ...burdens of these SPAs, with the exception of 2,6-di-tert-butyl-4-methylphenol (BHT). In our study, BHT as well as six other SPAs were analyzed in human urine samples from United States donors. Three SPA congeners were detected in human urine: BHT, 2,4-di-tert-butylphenol (DBP), and 3-tert-butyl-4-hydroxyanisole (BHA). BHT, which is the congener received most concerns, was detected at low concentrations geometric mean (GM): 0.06 ng/mL, whereas four of its metabolites were detected at relatively high concentrations (GM: 1.68 ng/mL). Surprisingly, DBP was detected at extremely high concentrations (GM: 18.3 ng/mL). The concentrations of DBP (GM: 25.8 ng/mL), BHT (0.853 ng/mL), and metabolites (GM: 10.5 ng/mL) increased significantly after the urine samples were hydrolyzed by β-glucuronidase (p < 0.01), indicating the prevalence of the conjugated forms of SPAs and their metabolites in human urine. DBP, which has previously received little attention, was the predominant congener, contributing 88.2% and 63.6% to total target concentrations in the urine samples before and after β-glucuronidase hydrolysis, respectively. Thus, previous studies have vastly underestimated the burdens of SPAs to humans. To our knowledge, this is the first study revealing the presence of DBP in human urine.
Display omitted
•Three SPAs were detected in human urine from U.S. donors.•Four BHT metabolites were also detected.•Total concentrations of phenolic targets are higher than the free concentrations.•DBP was the primary congener in human urine.
Unexpectedly high concentrations of DBP were detected in human urine for the first time, which contributed >60% to total target concentrations.
•Methodology for ageing characterization based on the phenol index value implemented.•The phenol index allows for assessment of partly oxidized phenolic antioxidants.•Single-, double- and ...triple-oxidized products of irganox 1330 were monitored.•Embrittlement of the PP-R material was ascertained at a phenol index of 1.0.•A bilinear arrhenius relationship with a transition at 110 °C was obtained.
This paper deals with the hot air ageing behaviour of a polypropylene random copolymer (PP-R) model material in a wide temperature range from 65 to 135°C. The PP-R grade was stabilized with a blend of the phenolic antioxidants Irganox 1330 and 1010. To avoid diffusion-limited oxidation effects, micro-specimen with a thickness of 100 µm were investigated. As main ageing indicator the phenol index was evaluated from FTIR-spectra in transmittance mode. The oxidation of the functional phenolic groups was associated with a shift of the absorption peak by 18 and 35 cm-1 of the single- and dual-oxidized phenolic antioxidant Irganox 1330. The implemented FTIR evaluation approach was validated by high-pressure liquid chromatography hyphenated with mass spectroscopy and ultraviolet detection. Gaussian fitting of the triple IR-peak confirmed temperature dependent differences in the degradation pathways of the phenolic antioxidants. The decay of phenol index and the obtained endurance time exhibited a bilinear Arrhenius like behaviour with a transition temperature at 110°C, which was in agreement with the onset of melting of small crystal lamellae. The activation energy values were 94 and 32 kJ mol-1 above and below the transition temperature, respectively.
Display omitted
Synthetic phenolic antioxidants (SPAs) are of emerging concern due to their potential environmental risks. However, the environmental occurrence and fate of SPAs are poorly understood. In this study, ...13 SPAs were analyzed in 70 liquid and 21 solid samples from 12 wastewater treatment plants (WWTPs) in 2016 to investigate the distribution and composition of SPAs in different wastewater treatment processes in Canada. Wastewater samples were liquid-liquid extracted and biosolids were treated using ultrasonic assisted solvent extraction. SPAs were analyzed by ultra-performance liquid chromatography-tandem mass spectrometry. The concentrations of total SPAs were in the ranges of 71–3193 ng L−1 in influent, less than method quantification limits (MQLs)-520 ng L−1 in effluent, and 479–4794 ng g−1 in biosolids (dry weight (dw)). SPAs were effectively removed (median >75%) from the liquid stream in most WWTPs. In one aerated lagoon and two primary treatment sites, low removal efficiency (median −26%-43%) was observed for 4-tert-octylphenol (4-tOP). These results indicate that wastewater effluent is a vector for SPAs, including the endocrine disruptor 4-tOP, to aquatic environments. The mass balance approximation found major removal mechanisms are sludge sorption/separation and degradation. A preliminary risk assessment suggested that most SPAs in WWTP effluent were unlikely to pose ecotoxicological risks to aquatic organisms in the receiving waters. Future research should evaluate the environmental risks of SPAs associated with land application of biosolids and investigate the occurrence and fate of the degradation products of these contaminants.
Display omitted
•The single phenolic ring 4-tOP, 2,4-DTBP and BHT were the dominant SPAs in Canadian WWTPs.•Chemically assisted primary treatments showed very low removal efficiency of 4-tOP (−13 ± 43%).•The removal mechanisms included sludge sorption/separation and degradation in WWTP liquid stream.•Most target SPAs were unlikely to pose risks to aquatic organisms in Canadian WWTP effluent receiving waters.
Synthetic phenolic antioxidants (SPAs) are an environmental concern because they are widely detected in aquatic ecosystems and can pose potential threats to organisms. Studies have reported ...developmental deficits and behavioral changes in response to SPAs, indicating possible neurotoxic effects. However, their neuroactive potency as well as their mode of action (MoA) remain unclear. As such, this study evaluated the potential neurotoxicity of three SPAs butylated hydroxytoluene (BHT), 2,4-di-tert-butylphenol (2,4-DTBP), and 4-tert-octylphenol (4-t-OP) at three concentrations (0.01, 0.1 and 1 μM) to zebrafish larvae. Both 2,4-DTBP and BHT decreased spontaneous tail coiling (STC) at 28 hpf (hours post fertilization) whereas 4-t-OP increased STC. Locomotor activity, based on the velocity and distance of larvae (144 hpf) travelled, was promoted by 2,4-DTBP while it decreased in larvae with exposure to 4-t-OP and BHT. In the light-dark preference assay, exposure to either 2,4-DTBP or BHT resulted in variability in the visiting frequency to the dark zone, and larvae (144 hpf) spent less time in the dark, suggesting anxiety-like behavior. Conversely, zebrafish exposed to 4-t-OP, especially at 1 μM concentration, were hypoactive and spent more time in dark, suggestive of anxiolytic-like responses. RNA-seq was conducted to discern mechanisms underlying behavioral responses. Transcriptomic analysis revealed that gene networks related to neuroactive ligand-receptor interaction as well as neurotransmitter-related pathways were altered by all three SPAs based on gene set and subnetwork enrichment analysis. Modulation of dopaminergic, serotoninergic, and/or GABAergic signaling at the transcript level was noted for each of the three SPAs, but different expression patterns were observed, indicating SPA- and dose-specific responses of the transcriptome. The present study provides novel insight into potential mechanisms associated with neurotoxicity of SPAs congeners.
Display omitted
•Synthetic phenolic antioxidants (SPAs) cause neurotoxicity in developing zebrafish.•SPAs congeners divergently affected behavioral responses and transcriptome.•Steroid biosynthesis and neurotransmitter related pathways enriched.•Transcriptional levels of serotonin, dopamine, and GABA system were altered.
The enhancement of cold flow properties (CFPs) and oxidative stability (OS) in biodiesel-diesel blends typically involves the use of pour point depressants and antioxidants. However, a scant number ...of additives are capable of manifesting both pour point depression and antioxidant functionalities concurrently. This study explored the grafting of syringic acid (SA), 3,5-di-tert-butyl-4-hydroxybenzoic acid (DTBHA), and gallic acid (GA) onto polymethacrylate (PMA) type copolymers, culminating efficacious copolymers, namely PTG-SA, PTG-DTBHA and PTG-GA. The findings reveal that with the addition of 1500 ppm of PTG-GA, the CFPP and PP of B20 (20 vol% soybean biodiesel+80 vol% diesel) decrease by 10 and 18 °C respectively, and with the addition of 2000 ppm, the induction period (IP) of B20 can be extended from 1.34 to 8.69 h. In contrast, the application of PTG-SA and PTG-DTBHA to B20 led to inferior OS and CFPs as compared to PTG-GA. The inherent scientific mechanism that underlies this performance discrepancy was thoroughly investigated, scrutinizing it through the lens of co-crystallization and nucleation processes. This research underscores the potential of post-modification of PMA type pour point depressants with antioxidants, a strategy that not only bolsters the CFPs of B20 but also confers antioxidant attributes to the pour point depressants.
Display omitted
Display omitted
•ChCl-MaA exhibited to be a greatly green solvent in phenolic antioxidants extraction.•Parameters of ChCl-MaA-based UAE were optimized by using singer-factor along with ...RSM.•ChCl-MaA-based UAE extracts showed strongest antioxidant activities.•Partridge leaf-tea (PLT) can be considered as a good source rich in natural antioxidants.•Phenolic constituents of the PLT extracts were quantified and compared.
Herein, high efficient extraction of natural antioxidants from partridge leaf-tea (PLT) was carried out by using eco-friendly choline chloride-based deep eutectic solvents combined with ultrasonic method. Choline chloride-malic acid (ChCl-MaA), a new type of green solvent, with the highest efficient for extracting the natural antioxidants from PLT (DPPH-756.70 ± 12.13 μmol TE/g DW; FRAP-4139.17 ± 65.79 μM Fe(Ⅱ)SE/g DW) was screened for further optimization. The key parameters for simultaneously maximizing total phenolic content (TPC), total flavonoid content (TFC), 2,2-diphenyl-1-picrylhyldrazyl (DPPH) and ferric reducing antioxidant activity (FRAP) were optimized by single-factor experiments along with response surface methodology (RSM). Results exhibited that L/S ratio and water content in DES had significant effects on TPC and antioxidant activities, while ultrasonic power indicated a significant negative effect on all responses. Under the optimal conditions (ultrasonic power at 210 W, ultrasonic time at 30 min, L/S ratio at 27.50:1, water content in DES at 45%), experimentally obtained results were obtained as follows: 42.20 ± 2.17 mg GAE/g DW for TPC, 30.33 ± 2.16 mg RE/g DW for TFC, 838.64 ± 12.81 μmol TE/g DW for DPPH, and 5958.33 ± 153.52 μM Fe(Ⅱ)SE/g DW for FRAP, which were well in agreement with the predicted values. Furthermore, ChCl-MaA-based ultrasonic assisted extraction (UAE) yielded higher TPC, TFC and antioxidant activities compared with traditional solvents-based UAE. Strong antioxidant activities of PLT extracts were correlated with high levels of individual antioxidants including salvianic acid A, 3-chlorogenic acid, gallic acid, catechin and rutin. The functional groups analysis by Fourier transform infrared spectroscopy (FT-IR) were used to compare the solvents characterization before and after extraction. Scanning electron microscope (SEM) results further verified ChCl-MaA intensified the destruction of cell wall structure, and thereby allowed greater release of antioxidants from PLT. This work provides an eco-friendly ChCl-MaA-based UAE technique for efficiently extraction and valorization of phenolic compounds from PLT, which can be further used in pharmaceutical, food, and cosmetic industries.
