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AbstractContext Cephaeline is a natural product isolated from ipecac (Cephaelis ipecacuanha [Brot.] A. Rich. [Rubiaceae]). It exhibits promising anti-lung cancer activity and ferroptosis induction may be a key mechanism for its anti-lung cancer effect.Objectives This study investigates the anti-lung cancer activity and mechanisms of cephaeline both in vitro and in vivo.Materials and methods H460 and A549 lung cancer cells were used. The cephaeline inhibition rate on lung cancer cells was detected via a Cell Counting Kit-8 assay after treatment with cephaeline for 24 h. Subsequently, the concentrations of 25, 50 and 100 nM were used for in vitro experiments. In addition, the antitumour effects of cephaeline (5, 10 mg/kg) in vivo were evaluated after 12 d of cephaeline treatment.Results Cephaeline showed significant inhibitory effects on lung cancer cells, and the IC50 of cephaeline on H460 and A549 at 24, 48 and 72 h were 88, 58 and 35 nM, respectively, for H460 cells and 89, 65 and 43 nM, respectively, for A549 cells. Meanwhile, we demonstrated that ferroptosis is the key mechanism of cephaeline against lung cancer. Finally, we found that cephaeline induced ferroptosis in lung cancer cells by targeting NRF2.Discussion and conclusion We demonstrated for the first time that cephaeline inhibits NRF2, leading to ferroptosis in lung cancer cells. These findings may contribute to the development of innovative therapeutics for lung cancer.

A simple voltammetric method, employing Au nanoparticles modified glassy carbon electrode (AuNPs/ GCE), was developed for the determination of butylated hydroxylanisole (BHA), butylated hydroxytoluene (BHT), and tert-butylhydroquinone (TBHQ), the widely used synthetic phenolic antioxidants in foods. As a result, the electrochemical behavior of the antioxidants could be simultaneously detected only at the AuNPs/ GCE. The AuNPs/GCE allowed the detection of the three analytes at potentials lower than those observed at bare GCE. The stability and repeatability of the AuNPs/GCE were also confirmed in the study. Under the optimized conditions, the method presented a linear response in the concentration range of 0~330 mg/ L for TBHQ (R² = 0.9962), BHA (R² = 0.9974) and BHT (R² = 0.9968), respectively. The proposed method was effectively utilized to simultaneously quantify BHA, BHT, and TBHQ in various edible oil products. The obtained results were found to be consistent with those obtained through the high-performance liquid chromatography (HPLC) method. The analytical utility of the AuNPs/GCE-based sensor was evaluated through a recovery study, achieving an average recovery of 95.56% to 104.98% for the three antioxidants. These results indicated satisfactory precision and accuracy, suggesting the potential use of the developed electroanalytical method for detecting these antioxidants in food products. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study aimed to investigate the impact of tert-butylhydroquinone (TBHQ), chitosan, and their combination on memory and neurobiochemical parameters in a rat model. The primary objectives were to assess the cognitive effects of TBHQ, explore the cognitive-enhancing properties of chitosan, and evaluate the combined effects of these substances. MATERIALS AND METHODS: A rat model was employed for behavioral tests, biochemical analyses, and histological examinations. Rats were exposed to TBHQ, chitosan, or a combination of both, and cognitive function was assessed through behavioral tests. Biochemical analyses focused on neurobiochemical parameters associated with memory and oxidative stress. Histological examinations were conducted to observe any structural changes in the brain. RESULTS: TBHQ exposure was associated with memory impairments and increased oxidative stress, indicating potential neurotoxic effects. Chitosan supplementation demonstrated cognitive-enhancing effects and showed promise in mitigating the memory impairments and oxidative stress induced by TBHQ. The combination of chitosan and TBHQ presented a potential protective effect on neurological health. CONCLUSIONS: Chitosan supplementation alongside TBHQ may mitigate memory impairments and oxidative stress associated with TBHQ exposure in a rat model. The study provides valuable insights into the cognitive effects of TBHQ and the neuroprotective potential of chitosan, highlighting the need for further research to elucidate molecular pathways and clinical implications. These findings contribute to understanding chitosan's role in safeguarding neurological health in conditions where TBHQ exposure is a concern, warranting further investigations for translational applications in human health. [ABSTRACT FROM AUTHOR]

Summary: Neonatal platelets present a reduced response to the platelet agonist, thrombin (Thr), thus resulting in a deficient Thr‐induced aggregation. These alterations are more pronounced in premature newborns. Here, our aim was to uncover the causes underneath the impaired Ca2+ homeostasis described in neonatal platelets. Both Ca2+ mobilization and Ca2+ influx in response to Thr are decreased in neonatal platelets compared to maternal and control woman platelets. In neonatal platelets, we observed impaired Ca2+ mobilization in response to the PAR‐1 agonist (SFLLRN) or by blocking SERCA3 function with tert‐butylhydroquinone. Regarding SOCE, the STIM1 regulatory protein, SARAF, was found overexpressed in neonatal platelets, promoting an increase in STIM1/SARAF interaction even under resting conditions. Additionally, higher interaction between SARAF and PDCD61/ALG2 was also observed, reducing SARAF ubiquitination and prolonging its half‐life. These results were reproduced by overexpressing SARAF in MEG01 and DAMI cells. Finally, we also observed that pannexin 1 permeability is enhanced in response to Thr in control woman and maternal platelets, but not in neonatal platelets, hence, leading to the deregulation of the Ca2+ entry found in neonatal platelets. Summarizing, we show that in neonatal platelets both Ca2+ accumulation in the intracellular stores and Thr‐evoked Ca2+ entry through either capacitative channels or non‐selective channels are altered in neonatal platelets, contributing to deregulated Ca2+ homeostasis in neonatal platelets and leading to the altered aggregation observed in these subjects. [ABSTRACT FROM AUTHOR]

This paper discusses the potential of tert-butylhydroquinone (TBHQ), butylated hydroxyanisole (BHA) and alpha-tocopherol (α-T) in preventing palm biodiesel oxidation over an extended storage period of twelve weeks. A combination of Fourier transform infrared spectroscopy (FTIR), gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC) analyses were carried out. The FTIR spectra showed no significant changes to the carbonyl band at 1740 cm−1 across the storage period for fuels with additives, but the control had increased band intensity, which implied that additives prevented the formation of byproducts which have carbonyl groups or cyclic ether rings. From GC-MS analyses, lower transmittance at C18 methyl esters region was evident of methyl oleate, methyl linoleate and methyl linolenate being consumed to the point where their concentrations dropped below those of methyl palmitate in the sample without additives. Furthermore, the analyses indicated that 3-octyl-oxiraneoctanoic acid ME, E−10,13,13-trimethyl-11-tetradecen-1-ol acetate and 17-octadecynoic acid ME were the major oxidation byproducts. Traces of acetal, carboxylic acid, oxirane and alkylnoic acid were also detected. It was shown through HPLC analyses that TBHQ, BHA and α-T were consumed with α-T samples having the highest consumption compared to TBHQ and BHA. Overall, the findings supported the important role of additives in stabilizing the fuel and preventing oxidation during extended storage.

Simple Summary: In poultry feed, the oxidative rancidity of lipids is an important factor that affects the quality of feed and the safety of poultry products. Therefore, it is very important to choose and apply antioxidant substances. Tert-butylhydroquinone (TBHQ) is a new and highly effective antioxidant for feeds. However, there is limited information about the effects of TBHQ on animals or poultry in vivo. Moreover, tea polyphenols (TP) are a natural antioxidant that can prevent and treat diseases by scavenging free radicals and regulating the activity of different types of oxidases in the body. This study comprehensively evaluated the effects of a complex antioxidant, the main components of which are TBHQ and TP, on growth performance, meat quality, and antioxidant capacity in broilers. The obtained results revealed that supplementing diets with optimal amounts of TBHQ and TP contributed to serum and liver antioxidant capacity, thereby improving the growth performance and meat quality of broilers. This study aimed to evaluate the effects of diets supplemented with various levels of complex antioxidants (CA) containing tertiary butylhydroquinone (TBHQ) and tea polyphenols (TP) on growth performance, meat quality of breast and leg muscles, serum biochemistry, and antioxidant capacity of serum, liver, breast meat, jejunum, and ileum in broilers. A total of 600 one-day-old Arbor Acres male broilers with similar body weights were randomly divided into three groups (10 replicates/group, 20 broilers/replicate). Birds in the three experimental groups were fed a basal diet with CA at 0, 300, and 500 mg/kg. The results showed that supplementing with 300 mg/kg CA significantly increased (p < 0.05) 42 d BW and 22–42 d ADG, and markedly decreased (p < 0.05) 22–42 d F: G ratio in comparison to the control group. Birds fed a diet with 300 mg/kg CA had a higher (p < 0.05) pH of chicken meat at 24 h and 48 h post mortem and lower (p < 0.05) yellowness values (b*) of chicken meat at 45 min and 24 h post mortem, along with a lower (p < 0.05) cooking loss. Supplementing with 300 mg/kg CA significantly increased (p < 0.05) serum and liver T-SOD activity, serum T-AOC level, as well as jejunual GST activity, and significantly decreased (p < 0.05) liver MDA content when compared with the control group. These results indicate that diet supplementation with 300 mg/kg CA containing TBHQ and TP could improve growth performance and meat quality by increasing the antioxidant capacity of broilers. [ABSTRACT FROM AUTHOR]

Nuclear factor e2–related factor 2 (Nrf2) plays a key role in cellular resistance to oxidative stress injury. Oxidative stress injury, caused by Nrf2 imbalance, results in increased pyroptosis, DNA damage, and inflammatory activation, which may lead to the arrest of alveolar development and bronchopulmonary dysplasia (BPD) in premature infants under hyperoxic conditions. We established a BPD mouse model to investigate the effects of tert-butylhydroquinone (TBHQ), an Nrf2 activator, on oxidative stress injury, pyroptosis, NLRP3 inflammasome activation, and alveolar development. TBHQ reduced abnormal cell death in the lung tissue of BPD mice and restored the number and normal structure of the alveoli. TBHQ administration activated the Nrf2/heme oxygenase-1 (HO-1) signaling pathway, resulting in the decrease in the following: reactive oxygen species (ROS), activation of the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome, and IL-18 and IL-1β expression and activation, as well as inhibition of pyroptosis. In contrast, after Nrf2 gene knockout in BPD mice, there was more severe oxidative stress injury and cell death in the lungs, there were TUNEL + and NLRP3 + co-positive cells in the alveoli, the pyroptosis was significantly increased, and the development of alveoli was significantly blocked. We demonstrated that TBHQ may promote alveolar development by enhancing Nrf2-induced antioxidation in the lung tissue of BPD mice and that the decrease in the NLRP3 inflammasome and pyroptosis caused by Nrf2 activation may be the underlying mechanism. These results suggest that TBHQ is a promising treatment for lung injury in premature infants with hyperoxia. [ABSTRACT FROM AUTHOR]

Abstract Background Metabolic syndrome (MetS) is regarded as a complex metabolic disorder. Recently, the role of dietary antioxidants in the underlying pathogenesis and complications of MetS has come into focus. Pistacia atlantica oil is known as a high antioxidant oil which might improve the antioxidant status of dietary oils and also oxidative stress markers. On the other hand, tert-Butylhydroquinone (TBHQ) is an approved food-grade synthetic antioxidant that acts both as an inducer and inhibitor of carcinogenesis. The current trial will explore the possible effect of a blend of Pistacia atlantica seed-canola oils, corn-canola oils with TBHQ, and corn-canola oil without TBHQ on oxidative stress markers in patients with MetS. Methods We will conduct a single-center, triple-blind, three-way randomized cross-over clinical trial (RCT) among 72 patients with MetS. After a 1-month run-in period, eligible participants will consume the intervention oils as their regularly consumed oils in a random order. Each intervention period will last 8 weeks separated by 4-week washout periods. Anthropometric indices, body composition, physical activity, blood pressure, and 24-h dietary food recall measurements will be assessed at the beginning and the end of each intervention period. The primary outcome will be oxidative stress markers including serum total antioxidant capacity, total oxidant status, malondialdehyde, nitric oxide, and the enzyme activity of myeloperoxidase, superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase. The secondary outcomes will be changes in MetS components including blood pressure, fasting blood glucose, triglyceride, high-density lipoprotein cholesterol, and anthropometric measurements. Discussion Pistacia atlantica seed oil is high in antioxidants. An intervention with this oil could offer an option for oxidative stress prevention among patients with metabolic syndrome. The present clinical trial will be the first one assessing the impact of Pistacia atlantica oil on human oxidative stress markers. Trial registration Iranian Registry of Clinical trials IRCT20130223012571N8 . Registered on 4 March 2022.

Introduction Thermal process is the most prominent option for treating foods. During the heat treatment, food nutrients response simultaneously but adversely under pH, temperature, moisture, and other provided conditions. It might result in an irreversible transformation of composition and structure that influences oxidative stability and sensory properties. The use of antioxidants is one of the most common methods to prevent edible oils oxidation. Safety concerns of synthetic antioxidants including tert-butylhydroquinone (TBHQ) as food additives have led to increasing demands for natural ones. Phenolic compounds such as Gallic Acid (GA) and Methyl Gallate (MG) represent to possess markedly high activity to scavenge free radicals which are among the most powerful natural sources of oxidative inhibitors in foods. Apart from their antioxidant activity, GA and MG also exhibit multiple biological characteristics such as anti-atherogenic, anti-spasmodic, and anti-microbial activities. This study aimed to investigate the oxidative stability of the in-use sunflower (S) and palm (P) oils as affected by the GA, MG, (GA+MG), and TBHQ to clarify their antioxidant behavior. Materials and Methods Antioxidants Gallic acid, Methyl gallate and TBHQ (Purity>98%) were purchased from Sigma Aldrich, USA. All solvents and chemicals were provided from Merck, Germany and Sigma Aldrich, USA with analytical grade. Antioxidant-free sunflower and palm oil were prepared from Three Goals factory, Neyshabur, and potatoes (Agria variety) from Fariman region, Khorasan Razavi. Results and Discussion Chemical changes, oxidative stability and quality indices of the in-use sunflower oil (S) and palm (P) (65:35 w.t. %) were evaluated during 8-hour heat treatment at 180 °C through GA, MG, GA/MG (25:75, 50:50 and 25:75) and TBHQ. All experiments were carried out in quadruplicate, and data were subjected to analysis of variance (One-way-ANOVA). Mean data were compared based on Duncan's multiple range test at 5% level (p

为提高牡丹籽油乳液的氧化稳定性，将叔丁基对苯二酚（TBHQ）与天然抗氧化剂（生育酚、抗坏血酸）进行复配，测定不同抗氧化剂对牡丹籽油乳液的抗氧化作用，并分析了不同复配抗氧化剂的相互作用机制。结果表明：在贮藏30 d时，添加和未添加抗氧化剂牡丹籽油乳液的粒径相较于0 d 均略有增加，200 mg/kg TBHQ与800 mg/kg抗坏血酸复配时乳液的Zeta电位绝对值最大，且抗氧化作用最强；TBHQ与抗坏血酸表现出较好的协同抗氧化作用，与生育酚表现出拮抗作用；TBHQ与生育酚之间拮抗作用的原因主要是TBHQ减少了生育酚在牡丹籽油乳液中油水界面的含量，而TBHQ与抗坏血酸之间协同作用主要是由于抗坏血酸增加了TBHQ在牡丹籽油乳液中油水界面的含量。综上，TBHQ与抗坏血酸复配能提高牡丹籽油乳液的氧化稳定性。In order to improve the oxidative stability of peony seed oil emulsion, tert-butylhydroquinone (TBHQ) was complexed with natural antioxidants (tocopherol and ascorbic acid), and the antioxidant effects of different antioxidants on the peony seed oil emulsion were determined and the mechanism of interaction between the different complexed antioxidants was analyzed. The results showed that the particle size of peony seed oil emulsion with and without antioxidants increased slightly at the 30 d of storage compared with that at the 0 d of storage. The absolute value of the Zeta potential of the emulsion added with 200 mg/kg TBHQ and 800 mg/kg ascorbic acid was the largest and the antioxidant effect was the strongest. TBHQ showed better synergistic antioxidant effect with ascorbic acid, and antagonistic effect with tocopherol. The antagonistic effect between TBHQ and tocopherol was mainly due to the fact that TBHQ reduced the content of tocopherol in the oil-water interface in peony seed oil emulsion, while the synergistic effect between TBHQ and ascorbic acid was mainly due to the fact that ascorbic acid increased the content of TBHQ in the oil-water interface in peony seed oil emulsion. In conclusion, the combination of TBHQ and ascorbic acid can effectively improve the oxidation stability of peony seed oil emulsion.

Background: Metabolic syndrome (MetS) is regarded as a complex metabolic disorder. Recently, the role of dietary antioxidants in the underlying pathogenesis and complications of MetS has come into focus. Pistacia atlantica oil is known as a high antioxidant oil which might improve the antioxidant status of dietary oils and also oxidative stress markers. On the other hand, tert-Butylhydroquinone (TBHQ) is an approved food-grade synthetic antioxidant that acts both as an inducer and inhibitor of carcinogenesis. The current trial will explore the possible effect of a blend of Pistacia atlantica seed-canola oils, corn-canola oils with TBHQ, and corn-canola oil without TBHQ on oxidative stress markers in patients with MetS. Methods: We will conduct a single-center, triple-blind, three-way randomized cross-over clinical trial (RCT) among 72 patients with MetS. After a 1-month run-in period, eligible participants will consume the intervention oils as their regularly consumed oils in a random order. Each intervention period will last 8 weeks separated by 4-week washout periods. Anthropometric indices, body composition, physical activity, blood pressure, and 24-h dietary food recall measurements will be assessed at the beginning and the end of each intervention period. The primary outcome will be oxidative stress markers including serum total antioxidant capacity, total oxidant status, malondialdehyde, nitric oxide, and the enzyme activity of myeloperoxidase, superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase. The secondary outcomes will be changes in MetS components including blood pressure, fasting blood glucose, triglyceride, high-density lipoprotein cholesterol, and anthropometric measurements. Discussion: Pistacia atlantica seed oil is high in antioxidants. An intervention with this oil could offer an option for oxidative stress prevention among patients with metabolic syndrome. The present clinical trial will be the first one assessing the impact of Pistacia atlantica oil on human oxidative stress markers. Trial registration: Iranian Registry of Clinical trials IRCT20130223012571N8. Registered on 4 March 2022. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the effects of diets supplemented with various levels of complex antioxidants (CA) containing tertiary butylhydroquinone (TBHQ) and tea polyphenols (TP) on growth performance, meat quality of breast and leg muscles, serum biochemistry, and antioxidant capacity of serum, liver, breast meat, jejunum, and ileum in broilers. A total of 600 one-day-old Arbor Acres male broilers with similar body weights were randomly divided into three groups (10 replicates/group, 20 broilers/replicate). Birds in the three experimental groups were fed a basal diet with CA at 0, 300, and 500 mg/kg. The results showed that supplementing with 300 mg/kg CA significantly increased (p < 0.05) 42 d BW and 22–42 d ADG, and markedly decreased (p < 0.05) 22–42 d F: G ratio in comparison to the control group. Birds fed a diet with 300 mg/kg CA had a higher (p < 0.05) pH of chicken meat at 24 h and 48 h post mortem and lower (p < 0.05) yellowness values (b*) of chicken meat at 45 min and 24 h post mortem, along with a lower (p < 0.05) cooking loss. Supplementing with 300 mg/kg CA significantly increased (p < 0.05) serum and liver T-SOD activity, serum T-AOC level, as well as jejunual GST activity, and significantly decreased (p < 0.05) liver MDA content when compared with the control group. These results indicate that diet supplementation with 300 mg/kg CA containing TBHQ and TP could improve growth performance and meat quality by increasing the antioxidant capacity of broilers.

Present embodiment is a study of evaluation of antioxidant property of bis-adamantylated resorcinol [4, 6- bis(1-adamantyl) resorcinol] 1b on nylon-12 as base polymer using differential scanning calorimetry (DSC) via oxidation induction time (OIT) studies. The DSC curves of 0.5% 1b mixed nylon-12 showed unusual pattern as it showed initially a hint of onset of oxidation but no prominent exotherm subsequently, thereby indicating no further oxidation of material. This behaviour showed that the 1b can be used as an antioxidant for variety of polymers. In this study, 1b has been functionalized to corresponding diamines 1bb which can be used for synthesis of bis-imides. 1b can itself be used as a precursor material for other polymers and active pharmaceutical ingredients. [ABSTRACT FROM AUTHOR]

The use of biolubricants as a replacement for petroleum-based products is becoming more and more important, due to the current global energy and crude oil scenario. Thus, the production of biolubricants (which could take place in biorefineries) should be as efficient as possible, obtaining high-quality products with suitable viscosity or oxidation stability values to compete with oil refineries. One of the ways to produce biolubricants is through double transesterification from vegetable oils, where the role of catalysts (usually homogeneous) is vital, as they can improve the yield of the process. However, they should be removed after the chemical reaction, which is difficult once the biolubricant is obtained. Otherwise, they could act as catalysts during oxidation, contributing to a further decrease in oxidation stability and provoking significant changes. To avoid this, antioxidant addition could be an interesting choice. The aim of this work was to assess TBHQ addition in frying oil biolubricants, monitoring properties such as viscosity, acid number, absorbance or TBHQ content (through voltammetry) during oxidation. TBHQ addition (2114 mg·L−1) kept the main quality parameters during oxidation compared to control samples. In contrast, TBHQ content decreased during oxidation (to 160 mg·L−1), which proved its antioxidant effect. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is one of the most common malignant tumors in the world, ranking fourth in incidence and second in mortality among malignant tumors. In recent years, there has been some progress in biological treatment and targeted treatment for gastric cancer, but the prognosis for gastric cancer patients remains pessimistic, and the molecular mechanisms involved are not yet clear. In this study, bioinformatics analysis showed that Ubiquitin-conjugating enzyme E2C(UBE2C) was abnormally expressed in various types of cancer. Furthermore, UBE2C protein and mRNA expression was significantly elevated in gastric cancer tissues and cells. Silencing UBE2C significantly inhibited the proliferation and migration of gastric cancer cells. Mechanistically, UBE2C overexpression inhibited gastric cancer cell autophagy, leading to the accumulation of p62. Furthermore, immunoprecipitation results showed that UBE2C overexpression promoted the interaction between p62 and KEAP1, while inhibiting the binding of NRF2 to KEAP1, thereby weakening the ubiquitination and degradation of NRF2. In addition, the silencing of UBE2C leads to a reduction in the nuclear accumulation of NRF2. Importantly, the NRF2 activator TBHQ reversed the inhibition of gastric cancer cell proliferation and migration caused by the silencing of UBE2C. In summary, our study provides new insights into the molecular mechanisms of UBE2C in anti-cancer therapy. • UBE2C is abnormally expressed in various types of cancer. • Knocking down UBE2C inhibits the proliferation and migration of gastric cancer cells. • UBE2C regulates the stability of NRF2 protein in gastric cancer cells. • UBE2C overexpression facilitated the interaction between p62 and KEAP1, while impeding the association between NRF2 and KEAP1. [ABSTRACT FROM AUTHOR]

The research on DNA adduct 8-OHdG formation is performed by reacting 2'-deoxyguanosine and H2O2 with acrylamide (AA) and TBHQ compounds that were exposed to UVA light. The 8-OHdG forming test was conducted at various incubation times (5 h and 7 h) and pH variations (7.4 and 8.4). The 8-OHdG formation was analyzed using a reversed-phase HPLC instrument using a buffer solution of sodium phosphate pH 6.7: methanol (85:15) as eluent. The results showed that samples containing TBHQ and acrylamide (AA) produced 8-OHdG and shows synergistic and antagonistic effects. The 8-OHdG level of mixing acrylamide (AA) and TBHQ compounds increased significantly when exposed to UVA light. Samples incubated with UVA exposure had higher levels of 8-OHdG than samples without UVA exposure. The longer the incubation time, the greater the 8-OHdG content was produced. At pH 8.4, most of the samples resulted in greater 8-OHdG formation when compared to samples with the same mixture at pH 7.4. Samples with the greatest 8-OHdG formation results were found in samples containing 2'-deoxyguanosine, acrylamide (AA), TBHQ, and H2O2 at pH 8.4 with UVA light irradiation for 7h [ABSTRACT FROM AUTHOR]

The demand for processed foods relies heavily on synthetic antioxidants like TBHQ and BHA to prevent spoilage. However, their excessive use poses health risks, prompting regulatory measures in many countries to ensure food safety. In this concern, a proficient electrochemical sensor for the simultaneous detection of tert-butylhydroquinone (TBHQ) and butylated hydroxyanisole (BHA) was designed. A comparatively greener hydroxyapatite (HAP) supported zinc ferrite (ZF) nanosensor was developed with conducting coating of Pd nanoparticles. A consolidated and mechanistic approach was opted to reduce the band gap and agglomeration the magnetic ZF nanoparticles. The interesting spherocuboidal morphology of the synthesized nanocomposite with good porosity enhanced the detection performance of the sensor. The proposed platform displayed good detection limits of both TBHQ and BHA (0.73 and 5.6 nM for TBHQ and BHA, respectively). The nanosensor successfully detected TBHQ and BHA in food samples proved its potential for the development of commercially competitive sensor., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors confirm the absence of any known competing financial interests or personal relationships that might have influenced the outcomes presented in this research work., (Copyright © 2024. Published by Elsevier Ltd.)

Food additives enhance sensory pleasure and improve marketability in food product formulations, yet their potential health risks are highly consequential. Tertiary butylhydroquinone (TBHQ), in this regard, has a controversial reputation owing to its neurotoxic effects, which include convulsions and other chronic issues. This situation underscores the need for an advanced electrochemical sensing platform. The current study advocates the utilization of copper tungstate nanoparticles to enhance the sensitivity, selectivity, and efficiency in TBHQ detection, thus addressing the challenges posed by the excessive use of additives and safeguarding the integrity of the food supply chain. Hydrothermally synthesized CuWO 4 nanoparticles exhibited superior physicochemical and morphological characteristics, bringing about wide linear response ranges (0.01 to 789 μM), high selectivity, excellent anti-interference capabilities, and a low detection limit of 0.9 nM (S/N = 3). The CuWO 4 modified screen printed carbon electrode (SPCE) presents promising recovery ranges in food samples, facilitating real-time monitoring and streamlining the quality assessment of food additives., Competing Interests: Declaration of competing interest There are no conflicts of interest in this work., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Aims: Tert-butylhydroquinone (tBHQ) has been identified as an inhibitor of oxidative stress-induced injury and apoptosis in human neural stem cells. However, the role of tBHQ in osteoarthritis (OA) is unclear. This study was carried out to investigate the role of tBHQ in OA. Methods: OA animal model was induced by destabilization of the medial meniscus (DMM). Different concentrations of tBHQ (25 and 50 mg/kg) were intraperitoneally injected in ten-week-old female mice. Chondrocytes were isolated from articular cartilage of mice and treated with 5 ng/ml lipopolysaccharide (LPS) or 10 ng/ml interleukin 1 beta (IL-1β) for 24 hours, and then treated with different concentrations of tBHQ (10, 20, and 40 μM) for 12 hours. The expression levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in blood were measured. The expression levels of interleukin 6 (IL-6), IL-1β, and tumour necrosis factor alpha (TNF-α) leptin in plasma were measured using enzyme-linked immunoabsorbent assay (ELISA) kits. The expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) signalling pathway proteins, and macrophage repolarization-related markers, were detected by western blot. Results: Tert-butylhydroquinone significantly attenuated cartilage destruction in DMM-induced mice in vivo. It demonstrated clear evidence of inhibiting IL-1β-induced chondrocyte apoptosis, inflammation, and differentiation defect in vitro. Meanwhile, tBHQ inhibited LPS-induced activation of NF-κB and MAPK signalling pathways, and also inhibited LPS-induced reactive oxygen species production and macrophages repolarization in vitro. Conclusion: Taken together, tBHQ might be a potential therapeutic strategy for protecting against OA development. Cite this article: Bone Joint Res 2021;10(11):704–713.

Aims: Oxidative stress plays a crucial role in podocyte injury in diabetic nephropathy (DN). tert-Butylhydroquinone (tBHQ) is an activator of Nrf2 that exerts protective effects in diabetic mice, but the underlying mechanism of tBHQ in the podocytes of DN is not fully understood. Materials and methods: A high glucose (HG)-induced HK2 cell model and streptozotocin-induced rat model of DN were established and treated with tBHQ or apocynin. The expression levels of Nrf2, HO-1, NOX2 and NOX4 were determined by Western blot or immunohistochemical staining. The level of oxidative stress in podocytes or kidney tissues was assessed using DCFH-DA or dihydroethidium (DHE) staining. Cell injury was assessed by F-actin staining and flow cytometry analysis. Key findings: We showed that HG treatment increased the expressions of NOX2 and NOX4 and enhanced ROS production in podocytes. Inhibition of NADPH oxidase activity by apocynin dramatically attenuated HG-induced ROS production and further alleviated cell injury and apoptosis in podocytes. Moreover, we found that HG inhibited the Nrf2/HO-1 signalling pathway in podocytes; however, tBHQ treatment significantly activated the Nrf2 signalling pathway, inhibited NADPH oxidase activity, and attenuated ROS production and cell injury in HG-treated podocytes. Furthermore, we observed that tBHQ treatment partially attenuated renal injury, activated the Nrf2 signalling pathway, inhibited NADPH oxidase activity and reduced ROS generation in the kidneys of STZ-induced diabetic rats. Significance: These results suggest that tBHQ exerts a protective role in hyperglycaemia-induced podocyte injury, and that the potential protective mechanism of tBHQ involves inhibiting NADPH oxidase-derived ROS generation by activating the Nrf2/HO-1 signalling pathway.

Objective: To investigate whether tert-Butylhydroquinone (TBHQ) can ameliorate oxidative stress and inflammation induced by glutamate excitotoxicity, and mediate retinal ganglion cell (RGC) damage by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway and inhibiting the nuclear factor kappa B (NF-κB) signaling pathway. Materials and methods: TBHQ was used to treat a glutamate excitotoxicity model of retinal cell line 28 and C57 mice. Damage to RGCs and visual function were assessed using flash visual evoked potential (FVEP), immunofluorescence, propidium iodide staining, and hematoxylin and eosin staining. Knockdown of Nrf2 used Nrf2 shRNA. The expression levels of related proteins were detected using western blot and immunofluorescence. Results: Glutamate excitotoxicity down-regulated Nrf2 expression in vitro and in vivo. Nuclear factor erythroid2-related factor 2 activation by TBHQ reduced the damage to retinal ganglion cells, reduced the thinning of the whole retina and the ganglion cell complex, and shortened the latency of the FVEP forward wave after injury. In addition, the levels of NAD(P)H quinone dehydrogenase 1 (NQO1), heme oxygenase 1 (HO-1), and Nrf2 increased significantly, and those of cyclooxygenase-2 (COX2) and NF-κB decreased significantly, after TBHQ treatment. Compared with TBHQ treatment group, the expression level of p-p65 in shRNA transfected group was increased, but still lower than that in Glu group. Conclusion: The protective effect of TBHQ on RGC loss under glutamate excitotoxicity might be related to the activation of the Nrf2 signaling pathway, anti-oxidative stress, inhibition of NF-κB activation, and inhibition of retinal inflammation. Thus, TBHQ might be used to treat glutamate excitotoxicity -related retinopathy.

The aim of this study was to encapsulate 2-tert-butylhydroquinone (TBHQ), as a common synthetic antioxidant in food industries, by mesoporous silica nanoparticles (MSNs) and their amine-functionalized nanoparticles (AP-MSNs). Release profiles of TBHQ from nanocarriers in the simulated body, gastric, and gastrointestinal fluids were investigated. In addition, the cytotoxicity effects of free-TBHQ, TBHQ-loaded MSNs (MSNs/TBHQ), and TBHQ-loaded AP-MSNs (AP-MSNs/TBHQ) were studied using MTT assay. Results showed that the AP-MSNs has a little effect on TBHQ loading percentage (2% increased), whereas it has a considerable effect on the TBHQ release pattern. Cell viability studies indicated that viability in treated cells by nanoparticles or free-TBHQ was in a time- and dose-dependent manner. For MSNs/TBHQ and AP-MSNs/TBHQ, a lower cytotoxicity was detected at different concentrations. Sustained release of TBHQ from nanocarriers with increase of its antioxidant activity was observed. The cellular uptake of MSNs/TBHQ and AP-MSNs/TBHQ by MCF-7 and HPHMF cells was confirmed by TEM images. [ABSTRACT FROM AUTHOR]

Food additives enhance sensory pleasure and improve marketability in food product formulations, yet their potential health risks are highly consequential. Tertiary butylhydroquinone (TBHQ), in this regard, has a controversial reputation owing to its neurotoxic effects, which include convulsions and other chronic issues. This situation underscores the need for an advanced electrochemical sensing platform. The current study advocates the utilization of copper tungstate nanoparticles to enhance the sensitivity, selectivity, and efficiency in TBHQ detection, thus addressing the challenges posed by the excessive use of additives and safeguarding the integrity of the food supply chain. Hydrothermally synthesized CuWO 4 nanoparticles exhibited superior physicochemical and morphological characteristics, bringing about wide linear response ranges (0.01 to 789 μM), high selectivity, excellent anti-interference capabilities, and a low detection limit of 0.9 nM (S/N = 3). The CuWO 4 modified screen printed carbon electrode (SPCE) presents promising recovery ranges in food samples, facilitating real-time monitoring and streamlining the quality assessment of food additives. [Display omitted] • Facile synthesis of CuWO 4 nanoparticles using hydrothermal method. • Electrochemical detection of Food Additive- TBHQ using CuWO 4 /SPCE. • Proposed sensor exhibited LOD and wide linear ranges towards CuWO 4 /SPCE. • Practicality of fabricated sensor in spiked TBHQ in milk and edible oil food samples. [ABSTRACT FROM AUTHOR]

Glutamate excitotoxicity can cause cell damage and apoptosis and play an important role in a variety of retinal diseases. Tertiary-butylhydroquinone (tBHQ) is an approved food-grade phenolic antioxidant with antioxidant activity in a variety of cells and tissues. We observed the protective effect of tBHQ on glutamatergic agonist-induced retina and explored its possible mechanism of action through in vitro cell experiments. The results showed that tBHQ had protective effects on NMDA-induced mouse retinal excitotoxicity and glutamate-induced excitotoxicity in rat retinal precursor cells (R28 cells). tBHQ reversed glutamate-induced apoptosis, production of intracellular reactive oxygen species, and reduction of mitochondrial membrane potential. Western blot analysis showed that tBHQ could increase the expression of procaspase-3, Bcl-2, AIF precursor, CAT, SOD2, Nrf2, NQO1, HO-1 and NF-κB in glutamate-treated cells, and decrease the expression of AIF cleavage products. Furthermore, we discovered that tBHQ activated müller glial cells. Based on these results, tBHQ may have antioxidant and anti-apoptotic properties, thus serving as a potential retinal protective agent. Its anti-oxidative stress effect was attributed to up-regulation of Nrf2, and its anti-apoptotic effect was related to its up-regulation of Bcl-2 expression and inhibition of mitochondria-dependent apoptosis.

The application of additives to the bio-lubricants is essential to improve the base oil tribological properties. A high-frequency reciprocating rig and different operating conditions were used to test the effects of tert-butylhydroquinone (TBHQ) and polytetrafluoroethylene (PTFE) polymer on the tribological performance of Ficus carica oil as a base oil for machine lubrication. The viscosity and Fourier transform infrared spectroscopy (FT-IR) evaluations were carried out to ascertain the additive's effectiveness. A scanning electron microscope was used to analyse the morphologies and the substrate-worn surfaces. When additives were applied separately, 1 wt% of PTFE produced a superior coefficient of friction (COF) and better wear reduction than other examined samples. In terms of wear resistance, commercial lubricant oil (CLO) SAE 5 W-30 performed better than the optimal 1 wt% PTFE + 0.3 wt% TBHQ blended with Ficus carica oil (FCO/L). At an increased frequency of 5 Hz, CLO outperformed FCO/L on COF and wear resistance. When examining the worn surfaces, less iron (Fe) was discovered on the FCO/L than the base Ficus carica oil, demonstrating the mending effect of the used additive as the underlying mechanism of wear reaction. The results show promising potential for the new formulation of a green lubricant since the tribological characteristics of Ficus carica oil were improved by the addition of the selected additives. [ABSTRACT FROM AUTHOR]

Background. tert-butylhydroquinone (tBHQ) is an antioxidant commonly used as a food additive. Studies suggest that tBHQ could modulate immune responses to influenza and SARS-CoV-2 infection. In our transcriptomic analysis we explored the molecular mechanisms behind tBHQ's modulatory properties and the relationships to respiratory viral infections. Methods. tBHQ was administered per os to BALB/c mice (1.5% [w/w]) for 20 days. Splenic T cells were isolated with magnetic separation and subjected to transcriptomic analysis. Gene-set enrichment analysis and g:Profiler was conducted to provide a functional interpretation of significantly changed genes. Further analysis for AHR/NRF2 binding sites was performed with GeneHancer. Results. In CD4+ cells, we found significantly altered expression of 269 genes by tBHQ. Of them, many had relevance in influenza infection such as genes responsible for virus entry (Anxa1/2, Cd14), interferon signaling (Dusp10, Tnfsf13), or prostaglandin synthesis (Ptgs1/2). In SARS-CoV-2 infections, interferon signaling (Ifitm1), proteolytic enzymes (CtsB), and also cell-surface proteins (Cd14, Cd151) were among the prominent alterations after tBHQ exposure. Of these genes, many had one or more binding sites for AHR and NRF2, two major xenosensors triggered by tBHQ. Conclusions. Our results strongly suggest that a common food additive, tBHQ, can modulate virus-dependent processes in both influenza and SARS-CoV-2 infections. [ABSTRACT FROM AUTHOR]

Chia oil (CO) has gained popularity given its α‐linolenic acid content (around 60%). Nonetheless, the susceptibility of polyunsaturated fatty acids toward oxidation represents a challenge for incorporating CO in different products, which justifies the need for exploring stabilization methods. To the best of the authors' knowledge, no reports about powders based on chia oil blends are published. Therefore, the objective of this research is to evaluate the stability at room temperature of microencapsulated CO blends [with virgin sesame (VSO) and wheat germ (WGO) oils] and microencapsulated CO with the addition of tert‐butylhydroquinone (TBHQ). Spray‐drying yielded powders with a better encapsulation efficiency, flowability, and stability, compared with freeze‐drying. After a storage test performed during 3 months, the highest hydroperoxide content (>100 meq.O2 kg−1 oil) is observed for the microencapsulated CO/WGO 80/20 blend, despite its α and β‐tocopherol contents and its antioxidant activity (>90% inhibition of DPPH radical). Notwithstanding, bulk and microencapsulated CO‐TBHQ, CO/VSO 80/20, and 20/80 showed hydroperoxide contents <8 meq.O2 kg−1 oil. By the end of the test, the highest induction period is observed for the microencapsulated CO/VSO 20/80 blend (19.85 ± 0.18 h). Finally, the drying method and the core formulation greatly affect the stability of microcapsules. Practical Applications: Addition of antioxidants, oil blending and microencapsulation are technological solutions for the preservation of omega‐3‐rich oils, which are popular among healthy food consumers. This research studies and compares the microencapsulation processes by spray or freeze‐drying in order to preserve chia oil blends (with virgin sesame and wheat germ oils) and chia oil with the addition of antioxidants, thereby taking the advantages of the three technological solutions mentioned above. Stable omega‐3‐rich powders, with a higher oxidative stability than pure chia oil, can be obtained as ingredients for the food industry. This ultimately allows the incorporation of the oil into different food products developed to satisfy specific market tendencies. [ABSTRACT FROM AUTHOR]

The frying process is one of the excellent ways for food to have ideal sensory. However, some harmful substances may also be produced, such as aldehydes and monoepoxy oleic acid. In this experiment, Camellia oleifera seed cake extract (CSCE) was used as the test material, and the antioxidant activity of the extract was evaluated by the determination ofantioxidant indexes. The synergistic effect of the extract and TBHQ in inhibiting oil oxidation was studied. The colorimetric method was used to determine total phenol content of the extract was determined by high performance liquid chromatography to determine the composition and content of polyphenols in the polyphenol extract of Camellia oleifera seed cake. The results show that CSCE can significantly reduce monoepoxy oleic acid. In addition, CSCE has a better inhibitory effect on monoepoxy fatty acids than TBHQ. Our results may help provide reference and guidance for finding new natural antioxidants. [ABSTRACT FROM AUTHOR]

Different antioxidant effects of adding tert-butylhydroquinone (TBHQ) to biodiesel in different processes of biodiesel production were investigated by determining oxidation stability during the biodiesel production process. The induction time of biodiesel prepared from waste animal and vegetable oils containing 0.10 wt% TBHQ was 10.9 h at 110 °C, the induction time increased with the increase of TBHQ concentration. While the antioxidant effect of adding the same concentration of antioxidant TBHQ was weakened with the extension of storage time (before TBHQ was added), the oxidation stability of the biodiesel decreased by 53.6% after 18 hours' placement. Similarly, when TBHQ was added in the production process, the induction time also extended with the increase of TBHQ concentration. With 0.06 wt% TBHQ added in the distillation process, the oxidation induction time of biodiesel obtained was 9.7 h, with 0.06 wt% TBHQ added in the reaction process, the oxidation induction time of biodiesel obtained was 14.27 h. As expected, for the same concentration, TBHQ displayed the highest effectiveness when added in the reaction process and showed better efficacy when used in the distillation process compared to adding in store stage. [ABSTRACT FROM AUTHOR]

目前，酚类抗氧化剂TBHQ的常用检测方法存在前处理烦琐、耗时长、单次只能测定一个样品的问题，因此亟需建立一种高通量、快速准确的检测方法。为此，将高效薄层色谱(HPTLC)分离与1，1-二苯基-2-三硝基苯肼(DPPH)还原变色反应、图像像素定量分析相结合，建立了一种快速筛检酚类抗氧化剂TBHQ的方法。在此基础上，以食用油、面包和蛋糕为代表性样品，验证所建方法的实际应用性能。结果显示：所建方法检测TBHQ的检测限为70 ng/zone (35 mg/kg)，定量限为140 ng/zone (70 mg/kg)，定量限低于GB 2760—2014规定的使用限量(200 mg/kg)；通过对比分析，样品提取物中共存的背景基质对目标物定量的干扰可以忽略，证明了该方法具有良好的选择性；目标物在150～550 ng/zone范围内表现出良好的线性（R2=0.989 2）；多次平行（n=3）测试和国标规定使用限量水平附近的加标回收率测试结果证明了该方法具有较好的精密度和准确度。综上，该方法具有基质耐受性强、定量准确、简便可靠且分析通量大等优点，特别适合粮油食品中各种抗氧化剂的快速定量筛查，具有凝炼成为相关领域国家标准的潜力和价值。 At present, the common detection methods of phenolic antioxidant TBHQ have the problems of cumbersome pretreatment, long time-consuming and can only determine one sample at a time. Therefore, it is urgent to establish a high-throughput, fast and accurate detection method. A rapid method for screening phenolic antioxidant TBHQ was established by combining high performance thin layer chromatography (HPTLC) separation with reduction discoloration reaction of 1,1-diphenyl-2-trinitrophenylhydrazine (DPPH) and quantitative analysis of image pixels. On this basis, edible oil, bread and cake were taken as representative samples to verify the practical application performance of the proposed method. The results showed that the detection limit of the established method to detect TBHQ was 70 ng/zone (35 mg/kg), the limit of quantification was 140 ng/zone (70 mg/kg), and the limit of quantification was lower than the limit of use (200 mg/kg) specified in GB 2760-2014. Through comparative analysis, the interference of the background matrix coexisting in the sample extract on the target quantity could be ignored, which proved that the method had good selectivity. The target showed good linearity in the range of 150-550 ng/zone (R2=0.989 2). Secondly, several parallel tests (n=3) and the test results of spiked recovery near the specified limit level of national standard proved that the method had good precision and accuracy. In summary, this method has the advantages of strong matrix tolerance, accurate quantification, simpleness and reliableness, and large analytical flux. Therefore, it is particularly suitable for rapid quantitative screening of various antioxidant additives in cereal and oil food, and has the potential and value of becoming a national standard in related fields.

Context: Cephaeline is a natural product isolated from ipecac ( Cephaelis ipecacuanha [Brot.] A. Rich. [Rubiaceae]). It exhibits promising anti-lung cancer activity and ferroptosis induction may be a key mechanism for its anti-lung cancer effect., Objectives: This study investigates the anti-lung cancer activity and mechanisms of cephaeline both in vitro and in vivo ., Materials and Methods: H460 and A549 lung cancer cells were used. The cephaeline inhibition rate on lung cancer cells was detected via a Cell Counting Kit-8 assay after treatment with cephaeline for 24 h. Subsequently, the concentrations of 25, 50 and 100 nM were used for in vitro experiments. In addition, the antitumour effects of cephaeline (5, 10 mg/kg) in vivo were evaluated after 12 d of cephaeline treatment., Results: Cephaeline showed significant inhibitory effects on lung cancer cells, and the IC 50 of cephaeline on H460 and A549 at 24, 48 and 72 h were 88, 58 and 35 nM, respectively, for H460 cells and 89, 65 and 43 nM, respectively, for A549 cells. Meanwhile, we demonstrated that ferroptosis is the key mechanism of cephaeline against lung cancer. Finally, we found that cephaeline induced ferroptosis in lung cancer cells by targeting NRF2., Discussion and Conclusion: We demonstrated for the first time that cephaeline inhibits NRF2, leading to ferroptosis in lung cancer cells. These findings may contribute to the development of innovative therapeutics for lung cancer.

An Au-based nanozyme composite (AuNPs/Cu,I) was constructed by using Cu,I-doped carbon dots (Cu,I-CDs) as the reducing agent as well as the nanozyme. Notably, AuNPs/Cu,I nanozyme not only possessed the intrinsic activity of mimicking enzymes of superoxide dismutase, peroxidase, and catalase at different conditions but was also employed as surface-enhanced Raman spectroscopy (SERS) enhancer. The combination of Cu,I-CDs and AuNPs promoted the electron transferability, leading to increased peroxidase-like activity and superoxide-like activity. Compared to the individual Cu,I-CDs and AuNPs nanozyme, the AuNPs/Cu,I composite demonstrated promising peroxidase-like activity by transferring electrons instead of generating OH. Interestingly, the multienzyme-like activity of AuNPs/Cu,I nanozyme could be finely tuned by changing the composition of Cu0/Cu+ and Au. The tert-butyl hydroquinone (TBHQ) as the substrate could be catalyzed with AuNPs/Cu,I nanozyme to produce red substances, resulting in a significant Raman enhancement effect at the same time, showing good linear range from 0.11 to 10 mg L−1. Overall, the current investigation provides a flexible and controllable way to design multifunctional nanozymes along with the Raman enhancement strategy based on the catalysis of nanozyme. [ABSTRACT FROM AUTHOR]

ABSTRACT: Fine particulate matter (PM2.5) from poultry houses has adverse effects on the health of animals and workers. Tert-butylhydroquinone (TBHQ), an antioxidant, is widely used in feed additives. The present study investigated the effects of TBHQ on broiler house PM2.5-induced damage in chicken primary alveolar epithelial cells (AECII) extracted from 16-day-old chicken embryos using the method of differential adhesion. AECII were exposed to PM2.5 and TBHQ alone or in combination, and then, cell membrane integrity, pyroptosis, and necroptosis were detected. Our results showed that PM2.5 from broiler houses caused cell rupture and loss of cell membrane integrity. This result was confirmed by the obvious increases in lactate dehydrogenase (LDH) release and propidium iodide (PI)-positive cells compared to the control group. In addition, the intracellular reactive oxygen species (ROS) levels and the expression levels of pyroptosis-related genes (NLRP3, IL-18, IL-1β) and necroptosis-related genes (RIPK3) were also significantly enhanced. However, TBHQ significantly inhibited intracellular ROS, improved cell viability, and reduced the release of LDH and the number of PI-positive cells compared to those in the PM2.5 group. The expression levels of pyroptosis-related genes (Caspase-1, NLRP3, IL-18, IL-1β) and necroptosis-related genes (RIPK3) were also significantly decreased in the co-treatment group. In summary, these results indicated that TBHQ can alleviate PM2.5-mediated cell pyroptosis and necroptosis in chicken AECII and provide a basis for overcoming the danger that air pollutants from broiler houses pose to the health of chickens.

Objectives: tert -Butylhydroquinone (TBHQ) is an antioxidant and preservative used in unsaturated vegetable oils and processed foods. However, when consumed in higher doses daily, it may pose a threat to public health by potentially increasing the risk of cancer, as it has an affinity with both the aryl hydrocarbon receptor (AhR) and the estrogen receptor alpha (ERα)., Methods: This study aimed to examine the impact of substituting the 1,4-diol of TBHQ with 1,4-dithiol, referred to as TBDT, on the carcinogenic and antioxidant systems using computational methods. The binding affinity of TBHQ and TBDT to the two carcinogenic receptors, AhR and ERα, as well as to the antioxidant receptor Keap1 alone and in connection with Nrf2 (Nrf2-Keap1) was investigated through docking analysis., Results: The results indicated a decrease in TBDT's binding strength to ERα and AhR when assessed using Molegro Virtual Docker ( P -value: 0.0001 and 0.00001, respectively), AutoDock Vina ( P -value: 0.0001 and 0.0001), and the online server Fast DRH ( P -value: 0.0001 and 0.0001). However, TBDT's binding affinity to Keap1 was predicted to be significantly stronger than TBHQ's by both MVD and AutoDock Vina ( P -value: 0.0001 and 0.04), while its binding to Nrf2-Keap1 assessed to be stronger only by MVD ( P -value: 0.0001)., Conclusion: These findings suggest that TBDT not only exhibits higher antioxidant activity as a better ligand for the antioxidant system but also shows lower affinity with the AhR and ERα receptors. Therefore, TBDT can be considered a safer compound than TBHQ., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The use of biolubricants as a replacement for petroleum-based products is becoming more and more important, due to the current global energy and crude oil scenario. Thus, the production of biolubricants (which could take place in biorefineries) should be as efficient as possible, obtaining high-quality products with suitable viscosity or oxidation stability values to compete with oil refineries. One of the ways to produce biolubricants is through double transesterification from vegetable oils, where the role of catalysts (usually homogeneous) is vital, as they can improve the yield of the process. However, they should be removed after the chemical reaction, which is difficult once the biolubricant is obtained. Otherwise, they could act as catalysts during oxidation, contributing to a further decrease in oxidation stability and provoking significant changes. To avoid this, antioxidant addition could be an interesting choice. The aim of this work was to assess TBHQ addition in frying oil biolubricants, monitoring properties such as viscosity, acid number, absorbance or TBHQ content (through voltammetry) during oxidation. TBHQ addition (2114 mg·L−1) kept the main quality parameters during oxidation compared to control samples. In contrast, TBHQ content decreased during oxidation (to 160 mg·L−1), which proved its antioxidant effect.

Oxidative stability of prototypical groundnut oil (GO) and mustard oil (MO) blended with a significant characteristic addition of antioxidants, α-tocopherol (α-T) and TBHQ (tert-butyl hydroquinone), at different concentrations was analysed. α-T (natural) and TBHQ (synthetic) antioxidants at a different concentrations from 0 to 20 mg/L were blended with GO and MO to prepare 18 samples. Compositional analysis of groundnut oil and mustard oil was carried out using gas chromatography and mass spectra (GCMS). Electrical properties like dielectric constant, tanδ, specific resistance etc. were investigated at frequencies from 1 Hz to 10 MHz for the modified samples. Thermal properties like breakdown voltage, flash and fire points and viscosity of all samples were also premeditated. It was observed that dielectric constant (ε′) of GO reduces from 3.58 to 2.82 with the addition of α-T but increases to 3.29 with the addition of TBHQ, whereas in MO, dielectric constant increases from 2.93 to 3.38 with the addition of α-T and rises to 3.27 with the addition of TBHQ at 15 mg/L. The synergistic effect of antioxidants in regulating the insulation nature of the oil is found to be more effective with α-tocopherol compared to TBHQ in GO. Higher breakdown voltage and more stability were observed in oil with the addition of antioxidant (TBHQ) in low concentration. The study would be useful in the selection of eco-friendly coolants in engineering and industry. [ABSTRACT FROM AUTHOR]

Following traumatic brain injury (TBI), increased production of reactive oxygen species (ROS) and the ensuing oxidative stress promotes the secondary brain damage that encompasses both grey matter and white matter. As this contributes to the long-term neurological deficits, decreasing oxidative stress during the acute period of TBI is beneficial. While NADPH oxidase (NOX2) is the major producer of ROS, transcription factor Nrf2 that induces antioxidant enzymes promotes efficient ROS disposal. We recently showed that treatment with an antioxidant drug combo of apocynin (NOX2 inhibitor) and TBHQ (Nrf2 activator) protects the grey matter in adult mice subjected to TBI. We currently show that this antioxidant combo therapy given at 2 h and 24 h after TBI also protects white matter in mouse brain. Thus, the better functional outcomes after TBI in the combo therapy treated mice might be due to a combination of sparing both grey matter and white matter. Hence, the antioxidant combo we tested is a potent therapeutic option for translation in future. [ABSTRACT FROM AUTHOR]

One of the major causes of long-term disability and mortality is ischemic stroke that enjoys limited treatment approaches. On the one hand, oxidative stress, induced by excessive generation of reactive oxygen species (ROS), plays a critical role in post-stroke inflammatory response. Increased ROS generation is one of the basic factors in the progression of stroke-induced neuroinflammation. Moreover, intravenous (IV) thrombolysis using recombinant tissue plasminogen activator (rtPA) as the only medication approved for patients with acute ischemic stroke who suffer from some clinical restrictions it could not cover the complicated episodes that happen after stroke. Thus, identifying novel therapeutic targets is crucial for successful preparation of new medicines. Recent evidence indicates that the transcription factor Nuclear factor erythroid 2-related factor 2 (Nrf2) contributes significantly to regulating the antioxidant production in cytosol, which causes antiinflammatory effects on neurons. New findings have shown a relationship between activation of the Nrf2 and glial cells, nuclear factor kappa B (NF-κB) pathway, the nucleotide-binding domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome signaling, and expression of inflammatory markers, suggesting induction of Nrf2 activation can represent a promising therapeutic alternative as the modulators of Nrf2 dependent pathways for targeting inflammatory responses in neural tissue. Hence, this review addresses the relationship of Nrf2 signaling with inflammation and Nrf2 activators' potential as therapeutic agents. This review helps to improve required knowledge for focused therapy and the creation of modern and improved treatment choices for patients with ischemic stroke. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract Background Maize oil is abundantly used in foods and feeds and is highly susceptible to oxidation. Consequently, commercially available antioxidants should be evaluated for effectiveness against lipid oxidation in swine diets. Our study was conducted to evaluate growth performance of nursery pigs fed oxidized maize oil and to determine effects of using antioxidants on oxidative status in a 2 × 2 factorial design. Two hundred eight weaned pigs were blocked by initial BW into 13 blocks, resulting in 4 pigs per pen and 13 pens per treatment. Dietary treatments included 6% unoxidized or oxidized maize oil, and 0 or 60 mg/kg of tert-butylhydroquinone (TBHQ), which was added after lipid oxidation. Data for growth performance were collected from 5 time periods of a two-phase feeding program (Phase 1 = d 0 to 12 and Phase 2 = d 13 to 34). Serum and liver samples were collected from one pig per pen, which had initial BW closest to average BW to determine oxidative status on d 34. Results Oxidized maize oil was heated for 12 h at 185 °C with 12 L/min of air, yielding a peroxide value (PV) of 5.98 mEq O2/kg and TBARS of 0.11 mg MDA eq/g. Addition of TBHQ to diets containing oxidized maize oil decreased PV by 37% and increased the oil stability index by 69%. Final BW, ADG, ADFI, and G:F of pigs were not different among the four dietary treatments. However, pigs fed oxidized maize oil tended (P

Summary: The interaction of tert‐butylhydroquinone (TBHQ) or chlorophyll with the oxidative phenomena involving oils has been previously reported. This study aimed to investigate the effects of TBHQ and chlorophyll on the polar compound composition of four vegetable oils during room‐temperature storage. Samples with different oxidation levels were collected. The results obtained showed that the major changes in polar compounds occurred in oxidised triglyceride (TAG) monomer (OxTG) content, whereas no evident change transpired in other components. The TBHQ‐added and chlorophyll‐added groups caused a decrease in the levels of OxTG in peanut and linseed oils. The chlorophyll‐added group contained high amount of OxTG in rapeseed oil, whereas no such phenomenon occurred in the TBHQ‐added group. This finding can be due to the antioxidant effect of chlorophyll in the dark. Therefore, the role of TBHQ or chlorophyll in TAG oxidation results from different phenomena that occur depending on the system and type of oil. [ABSTRACT FROM AUTHOR]

Background. tert-butylhydroquinone (tBHQ) is an antioxidant commonly used as a food additive. Studies suggest that tBHQ could modulate immune responses to influenza and SARS-CoV-2 infection. In our transcriptomic analysis we explored the molecular mechanisms behind tBHQ’s modulatory properties and the relationships to respiratory viral infections. Methods. tBHQ was administered per os to BALB/c mice (1.5% [w/w]) for 20 days. Splenic T cells were isolated with magnetic separation and subjected to transcriptomic analysis. Gene-set enrichment analysis and g:Profiler was conducted to provide a functional interpretation of significantly changed genes. Further analysis for AHR/NRF2 binding sites was performed with GeneHancer. Results. In CD4+ cells, we found significantly altered expression of 269 genes by tBHQ. Of them, many had relevance in influenza infection such as genes responsible for virus entry (Anxa1/2, Cd14), interferon signaling (Dusp10, Tnfsf13), or prostaglandin synthesis (Ptgs1/2). In SARS-CoV-2 infections, interferon signaling (Ifitm1), proteolytic enzymes (CtsB), and also cell-surface proteins (Cd14, Cd151) were among the prominent alterations after tBHQ exposure. Of these genes, many had one or more binding sites for AHR and NRF2, two major xenosensors triggered by tBHQ. Conclusions. Our results strongly suggest that a common food additive, tBHQ, can modulate virus-dependent processes in both influenza and SARS-CoV-2 infections.

Oxidative stress caused by mechanical ventilation contributes to the pathophysiology of ventilator-induced lung injury (VILI). A key mechanism maintaining redox balance is the upregulation of nuclear factor-erythroid-2-related factor 2 (Nrf2)-dependent antioxidant gene expression. We tested whether pretreatment with an Nrf2-antioxidant response element (ARE) pathway activator tert-butylhydroquinone (tBHQ) protects against VILI. Male C57BL/6J mice were pretreated with an intraperitoneal injection of tBHQ (n = 10), an equivalent volume of 3% ethanol (EtOH3%, vehicle, n = 13), or phosphate-buffered saline (controls, n = 10) and were then subjected to high tidal volume (HVT) ventilation for a maximum of 4 h. HVT ventilation severely impaired arterial oxygenation (PaO2" role="presentation">PaO2PaO2PaO2 = 49 ± 7 mmHg, means ± SD) and respiratory system compliance, resulting in a 100% mortality among controls. Compared with controls, tBHQ improved arterial oxygenation (PaO2" role="presentation" style="position: relative;">PaO2PaO2PaO2 = 90 ± 41 mmHg) and respiratory system compliance after HVT ventilation. In addition, tBHQ attenuated the HVT ventilation-induced development of lung edema and proinflammatory response, evidenced by lower concentrations of protein and proinflammatory cytokines (IL-1β and TNF-α) in the bronchoalveolar lavage fluid, respectively. Moreover, tBHQ enhanced the pulmonary redox capacity, indicated by enhanced Nrf2-depentent gene expression at baseline and by the highest total glutathione concentration after HVT ventilation among all groups. Overall, tBHQ pretreatment resulted in 60% survival (P < 0.001 vs. controls). Interestingly, compared with controls, EtOH3% reduced the proinflammatory response to HVT ventilation in the lung, resulting in 38.5% survival (P = 0.0054 vs. controls). In this murine model of VILI, tBHQ increases the pulmonary redox capacity by activating the Nrf2-ARE pathway and protects against VILI. These findings support the efficacy of pharmacological Nrf2-ARE pathway activation to increase resilience against oxidative stress during injurious mechanical ventilation. [ABSTRACT FROM AUTHOR]

Neonatal platelets present a reduced response to the platelet agonist, thrombin (Thr), thus resulting in a deficient Thr-induced aggregation. These alterations are more pronounced in premature newborns. Here, our aim was to uncover the causes underneath the impaired Ca 2+ homeostasis described in neonatal platelets. Both Ca 2+ mobilization and Ca 2+ influx in response to Thr are decreased in neonatal platelets compared to maternal and control woman platelets. In neonatal platelets, we observed impaired Ca 2+ mobilization in response to the PAR-1 agonist (SFLLRN) or by blocking SERCA3 function with tert-butylhydroquinone. Regarding SOCE, the STIM1 regulatory protein, SARAF, was found overexpressed in neonatal platelets, promoting an increase in STIM1/SARAF interaction even under resting conditions. Additionally, higher interaction between SARAF and PDCD61/ALG2 was also observed, reducing SARAF ubiquitination and prolonging its half-life. These results were reproduced by overexpressing SARAF in MEG01 and DAMI cells. Finally, we also observed that pannexin 1 permeability is enhanced in response to Thr in control woman and maternal platelets, but not in neonatal platelets, hence, leading to the deregulation of the Ca 2+ entry found in neonatal platelets. Summarizing, we show that in neonatal platelets both Ca 2+ accumulation in the intracellular stores and Thr-evoked Ca 2+ entry through either capacitative channels or non-selective channels are altered in neonatal platelets, contributing to deregulated Ca 2+ homeostasis in neonatal platelets and leading to the altered aggregation observed in these subjects., (© 2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

The worldwide incidence of traumatic brain injury (TBI) is ∼0.5% per year and the frequency is significantly higher among military personnel and athletes. Repetitive TBIs are associated with military and athletic activities, and typically involve more severe consequences. The majority of TBIs are mild; however, these still can result in long-term cognitive deficits, and there is currently no effective treatment. tert-Butylhydroquinone (tBHQ) and pioglitazone can activate the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and peroxisome proliferator-activated receptor-gamma (PPAR-γ) transcription factors, respectively, and each has been shown to be neuroprotective in various model systems. We examined behavioral and gene expression changes after repetitive mild TBI followed by simultaneous treatment with both factors. We used a repetitive closed head injury of mice involving five injuries with a 1-week interval between each TBI. We found that memory performance was significantly reduced by the injuries, unless the TBIs were followed by the tBHQ and pioglitazone administrations. Certain genes; for example, growth hormone and osteopontin, were downregulated by the injury, and this was reversed by the treatment, whereas other genes; for example, a tumor necrosis factor receptor, were upregulated by the injury and restored if the post-injury treatment was administered. Analysis of gene expression levels affected by the injury and/or the treatment point to potential mechanisms that could be exploited therapeutically. [ABSTRACT FROM AUTHOR]

Polypropylene (PP) based active composite films were prepared by adding butylated hydroxy anisole (BHA), butylated hydroxytoluene (BHT), and tertiary butylated hydroquinone (TBHQ) antioxidants using the extrusion molding process. All concentrations of BHT, 2% to 3% BHA, and 3% TBHQ significantly increased the tensile strength (TS) of the composite films compared with control films. Increasing antioxidant concentration decreased TS values for BHT films, whereas an opposite trend was observed for BHA and TBHQ films. BHA at < 2%, BHT at > 2%, and TBHQ at all added concentrations significantly reduced elongation at break (Eb) of the composite films compared to control films. Water vapor permeability (WVP) of 1% BHT film was not significantly different from control. However, other antioxidants especially at increased concentrations significantly increased WVP values. TBHQ films with 300% to 662% increase had the highest WVP and BHT films with 5% to 81% increase had the lowest WVP among composite films. All three antioxidants had a negative effect on the transparency of the films; however the effect of BHA at higher concentrations was greater. The antioxidants did not change the color attributes of the films. Films containing all antioxidants showed 2,2‐diphenyl‐1‐picrylhydrazyl radical‐scavenging activity, which increased with increase in their concentration, especially for those containing 3 wt.% BHT and TBHQ. Overall, incorporating BHA and BHT into a PP matrix improved mechanical, barrier, antioxidant properties, and film appearance and consequently were proposed for the development of antioxidant active PP films. TBHQ film is not recommended for food packaging because of its weak mechanical properties (lower Eb and TS values, higher WVP, and greater migration). [ABSTRACT FROM AUTHOR]

The antioxidants effect of two aminomethyl derivatives of 2-methoxyphenol: 4,6-di[(morpholin-4-yl)methyl]-2-methoxyphenol (DMMMP) and 5-[(pyrrolidin1-yl)methyl]vanillic acid (PMVA) on enhancing thermal and oxidative storage stability of coconut oil was performed using tert-butylhydroxyquinone (TBHQ) as a comparative standard. The efficacy on thermal stability test was carried out by heating at 180oC for 1, 3, and 6 hours, while the efficacy on the storage stability test was performed using an accelerated method by heating at 60oC for 5 weeks. The concentrations for MDMMP was 200, 350, and 500 ppm; for PMVA was 200, 275, and 350 ppm; and for TBHQ was 200 ppm. Free fatty acid (FFA) level, peroxide value (PV), and p-anisidine value (p-AV) were used as parameters to assess the level of oxidative stability of coconut oil. The results showed that the addition of DMMMP 200, 350, and 500 ppm, and PMVA 200 and 275 ppm did not inhibit FFA, peroxide, and aldehyde formation. In thermal stability study, PMVA (350 ppm) could inhibit the free fatty acid release, and formation of secondary oxidation products compounds on thermal stability comparable to TBHQ (200 ppm) addition, but only TBHQ that could inhibit peroxide formation for 6 h. In storage stability, DMMMP (all concentration) could not delay the fatty acid release, while PMVA (all concentration) and TBHQ (200 ppm) delayed that for 2 and 5 weeks, respectively. DMMMP (all concentration) delayed peroxide formation for 2 weeks, while PMVA (all concentration) and TBHQ (200 ppm) delayed peroxide formation for 5 weeks. All compounds only delay the formation of secondary oxidation products for 1 week. In conclusion, the efficacy of PMVA as an antioxidant against thermal and storage oxidative stability of coconut oil is higher than DMMMP but lower than TBHQ. [ABSTRACT FROM AUTHOR]

Biodiesel is an alternative to mineral fuels, with advantages such as biodegradability. However, this makes biodiesel unstable to oxidation. In this way, the use of natural or synthetic antioxidants is necessary. Although many studies have paid attention to the effect of these antioxidants on oxidation stability, not much literature about their effect of them on other properties (before and during storage) was found. The aim of this research study was to characterize biodiesel from corn and sunflower by adding two antioxidants, butylated hydroxyanisole (BHA) and tert‐butylhydroquinone (TBHQ), in order to improve its oxidation stability. Moreover, the effect of oxidation on the parameters of biodiesel was studied by using extreme oxidation conditions to accelerate the oxidation process. Both antioxidants improved the oxidation stability of biodiesel, whereas some parameters were altered (viscosity and acid number), which could make this biofuel, if high concentrations of antioxidants are used, unsuitable for commercialization according to standards. [ABSTRACT FROM AUTHOR]

Background: Hypertension is an increased risk of heart failure and acute myocardial infarction (MI). Tert-butylhydroquinone (tBHQ), as an antioxidant, shows multiple cardioprotective actions including the reduction in blood pressure. The aim of this study was to investigate whether and how tBHQ improves heart functions in rats. Methods: The MI model was established in WKY and spontaneously hypertensive rats (SHRs) by ligation of left anterior descending coronary artery. Akt phosphorylation was examined by western blot in human umbilical vein endothelial cells (HUVECs) or in rats. Angiogenesis was assessed by immunohistochemistry and immunofluorescence. Heart function was determined by echocardiography. Results: tBHQ increased Akt phosphorylation, promoted cell proliferations and migrations in HUVECs, which were abolished by Akt inhibitor wortmannin. In SHRs following MI, administration of tBHQ significantly increased Akt phosphorylation, promoted angiogenesis, reduced infarct size, and improved heart functions after 14 postoperative days. Importantly, these in vivo effects of tBHQ were ablated by wortmannin in SHRs. Conclusion: tBHQ via Akt activation promotes ischemia-induced angiogenesis and improves heart functions in hypertensive rats. In perspectives, the application of tBHQ should be considered in patients with ischemic diseases such as MI and stroke.

Ferroptosis is involved in the pathogenesis of osteoarthritis (OA) while suppression of chondrocyte ferroptosis has a beneficial effect on OA. However, the molecular mechanism of ferroptosis in OA remains to be elucidated. P21, an indicator of aging, has been reported to inhibit ferroptosis, but the relationship between P21 and ferroptosis in OA remains unclear. Here, we aimed to investigate the expression and function of P21 in OA chondrocytes, and the involvement of P21 in the regulation of ferroptosis in chondrocytes. First, we demonstrated that high P21 expression was observed in the cartilage from OA patients and destabilized medial meniscus (DMM) mice, and in osteoarthritic chondrocytes induced by IL-1β, FAC and erastin. P21 knockdown exacerbated the reduction of Col2a1 and promoted the upregulation of MMP13 in osteoarthritic chondrocytes. Meanwhile, P21 knockdown exacerbated cartilage degradation in DMM-induced OA mouse models and decreased GPX4 expression in vivo. Furthermore, P21 knockdown sensitized chondrocytes to ferroptosis induced by erastin, which was closely associated with the accumulation of lipid peroxides. In mechanism, we demonstrated that P21 regulated the stability of GPX4 protein, and the regulation was independent of NRF2. Meanwhile, we found that P21 significantly affected the recruitment of GPX4 to linear ubiquitin chain assembly complex (LUBAC) and regulated the level of M1-linked ubiquitination of GPX4. Overall, our results suggest that P21 plays an essential anti-ferroptosis role in OA by regulating the stability of GPX4., Competing Interests: Declaration of competing interest All authors disclosed no relevant relationships., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)