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Butylated hydroxytoluene (BHT) and its analogs, butylated hydroxyanisole (BHA) and tert-butyl-hydroquinone (TBHQ), are widely used synthetic preservatives to inhibit lipid oxidation in the food, cosmetic and pharmaceutical industries. Despite their widespread use, little is known about their human exposure and related biotransformation products. The metabolism of these compounds was investigated using in vitro incubations with human and rat liver fractions. Liquid chromatography coupled to high-resolution tandem mass spectrometry was employed to detect and characterize stable and reactive species formed via oxidative metabolism, as well as phase II conjugates. Several oxidative metabolites have been detected, as well as glutathione, glucuronide, and sulfate conjugates, many of which were not previously reported. A combination of accurate mass measurements, MS/MS fragmentation behavior, and isotope-labeling studies were used to elucidate metabolite structures.

This work analyses the performance and emission characteristics of biofuelled compression ignition (C.I) engine with the implementation of an antioxidant. Using the transesterification process with sodium hydroxide as a catalyst, the beef tallow methyl ester (BTME) was obtained from the beef tallow oil. Poor physical properties of biodiesel (beef tallow oil (BTO)) namely high viscosity and density cause atomization problems leading to higher smoke, hydrocarbon and carbon monoxide emissions. The purpose of this work is to enhance the performance aspects, to limit smoke emissions from BTO operation and to examine the possibility of direct use of neat BTO in CI engine. This research paves a way of investing the impact of binary blends of BHA and BTO on the research engine. The experiments were conducted on a single-cylinder four-stroke C.I engine using the following fuel compositions: 20% of BTME mixed with 80% diesel (B20), 1000 ppm mono-phenolic antioxidant (butylated hydroxyanisole (BHA)) mixed with the blends of B20 (B20 + BHA), and 100% diesel. Based on the experimental results, it was found that the brake thermal efficiency (BTE) increases by 1.8% and the brake specific fuel consumption (BSFC) decreases by 2.5% for the fuel blend B20 + BHA when compared with that for B20 fuel blend. Compared with the B20 blend, the blend B20 + BHA emits 12.2% lesser nitrogen oxide due to breaking chain reactions, scavenging the initiating radicals and reducing the concentration of reactive radicals.

This manuscript presents the impact of addition of antioxidant additives to rice bran biodiesel blend on the performance and emission characteristics of compression ignition (C.I) engine. Rice bran methyl ester (RBME) was produced from rice bran oil by transesterification using sodium hydroxide as catalyst. An experimental investigation was conducted on a single-cylinder four-stroke C.I engine to analyze the performance and emission characteristics of rice bran methyl ester (RBME) blended with diesel at 20% by volume (B20) with and without addition of 1000 ppm of two monophenolic antioxidant additives, butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT). The results showed that the BHA- and BHT-treated B20 blend decreased the brake specific fuel consumption (BSFC) by 2.1 and 1.2% and increased the brake thermal efficiency (BTE) by 1.04 and 0.5% compared to B20. The BHA- and BHT-treated B20 blend produced mean reductions in NOx emission of 12.2 and 9.6%, respectively, compared to B20. The carbon monoxide (CO) and hydrocarbon (HC) emissions of BHA- and BHT-treated B20 were increased by 14.8–16.6% and 10.6–11.2%, respectively, compared to B20. However the emission levels were lower than those of diesel.

Cells produce free radicals and antioxidants when exposed to toxic compounds during cellular metabolism. However, free radicals are deleterious to lipids, proteins, and nucleic acids. Antioxidants neutralize and eliminate free radicals from cells, preventing cell damage. Therefore, the study aims to determine whether the antioxidants butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) will ameliorate the maximum dose of acrylamide and alpha (α)-solanine synergistic toxic effects in exposed BEAS-2B cells. These toxic compounds are consumed worldwide by eating potato products. BEAS-2B cells were simultaneously treated with BHA 10 μM and BHT 20 μM and incubated in a 5% CO2 humidified incubator for 24 h, followed by individual or combined treatment with acrylamide (3.5 mM) and α-solanine (44 mM) for 48 h, including the controls. Cell morphology, DNA, RNA, and protein were analyzed. The antioxidants did not prevent acrylamide and α-solanine synergistic effects in exposed BEAS-2B cells. However, cell morphology was altered; polymerase chain reaction (PCR) showed reduced RNA constituents but not DNA. In addition, the toxic compounds synergistically inhibited AKT/PKB expression and its downstream genes. The study showed BHA and BHT are not protective against the synergetic toxic effects of acrylamide and α-solanine in exposed BEAS-2B cells.

The present study assessed the long-term daily administration of benzoic acid (BA), potassium sorbate (PS), chlorophyll (CPL), tartrazine (TAZ), and butylated hydroxyanisole (BHA) on hepato-renal changes and DNA damage in rats. Animals were orally administered with the 10 times of the acceptable daily intake (ADI) from each tested substance daily for 60 consecutive days. Blood, liver, and kidney samples were collected to evaluate hematological, biochemical, histopathological, and genotoxic alterations. The extent of liver and kidney damage was evaluated by comet assay and histopathologically. Significant reduction of leukocyte numbers and lymphocytes % in CPL- and TAZ-treated rats. However, significant increases in platelet count in all treated groups after 60 days were detected. The levels of serum transaminases enzymes (ALT, AST), alkaline phosphatase (ALP), and creatinine were significantly increased in all treatments except with BHA group, but no substantial differences were found in urea after 60 days. Aside from BHA, results of DNA damage revealed significant increases in tailed nuclei, tail moment, DNA% in the tail, and tail length in liver and kidney at different degrees. Moreover, the histopathological figures of liver and kidneys affirmed destructive and degenerative changes. The study indicates that most of the tested food additives may provoke genotoxicity and hepato-nephropathy, which could be serious for human health. Therefore, it is necessary to be informed about the hazardous effects of food additives and more attention should be focused towards using natural substitutes.

Based on previous findings that ozone can induce an inflammatory response in the ocular surface of an animal model and in cultured human conjunctival epithelial cells, we investigated whether exposure to ozone exacerbates symptoms of allergic conjunctivitis. We evaluated the effects of exposure to ozone on conjunctival chemosis, conjunctival injection, corneal and conjunctival fluorescein staining scores, production of inflammatory cytokines in tears, and aqueous tear production in a mouse model of allergic conjunctivitis. To validate our in vivo results, we used interleukin (IL)-1α-pretreated conjunctival epithelial cells as an in vitro substitute for the mouse model. We evaluated whether exposure to ozone increased the inflammatory response and altered oxidative status and mitochondrial function in IL-1α-pretreated conjunctival epithelial cells. In the in vivo study, ozone induced increases in conjunctival chemosis, conjunctival injection, corneal and conjunctival fluorescein staining scores, and production of inflammatory cytokines, accompanied by a decrease in tear volume. In the in vitro study, exposure to ozone led to additional increases in IL-6 and tumor necrosis factor-α mRNA levels, which were already induced by treatment with IL-1α. Ozone did not induce any changes in cell viability. Pretreatment with IL-1α increased the expression of manganese superoxide dismutase, and exposure to ozone led to additional increments in the expression of this antioxidant enzyme. Ozone did not induce any changes in mitochondrial activity or expression of mitochondrial enzymes and proteins related to mitochondrial function, with the exception of phosphor-mammalian target of rapamycin. Treatment with butylated hydroxyanisole, a free radical scavenger, attenuated the ozone-induced increases in IL-6 expression in IL-1α-pretreated conjunctival epithelial cells. Therefore, we conclude that exposure to ozone exacerbates the detrimental effects on the integrity of the ocular surface caused by conjunctival allergic reactions, and further increases the inflammatory response in IL-1α-pretreated conjunctival epithelial cells.

Most hepatocellular carcinomas (HCCs) develop in the context of chronic liver inflammation. Oxidative stress is thought to play a major role in the pathogenesis of HCC development. In this study, we examined whether cold‐inducible RNA‐binding protein (Cirp) controls reactive oxygen species (ROS) accumulation and development of HCC by using murine models of hepatocarcinogenesis and human liver samples. Cirp expression, ROS accumulation, and CD133 expression were increased in the liver of tumor‐harboring mice. Cirp deficiency reduced production of interleukin‐1β and interleukin‐6 in Kupffer cells, ROS accumulation, and CD133 expression, leading to attenuated hepatocarcinogenesis. Thioacetamide treatment enhanced hepatic expression of CD133 and phosphorylated signal transducer and activator of transcription 3 (STAT3), which was prevented by treatment with the antioxidant butylated hydroxyanisole. Intriguingly, the risk of human HCC recurrence is positively correlated with Cirp expression in liver. Cirp appears to play a critical carcinogenic function and its expression might be a useful biomarker for HCC risk prediction. Cirp would enhance tumorigenesis by controlling ROS accumulation. Cirp might be associated with stem cell maintenance. Cirp expression might be a useful biomarker for HCC risk prediction.

Potential mechanisms of Al toxicity measured as Al-induced inhibition of growth in cultured tobacco cells (Nicotiana tabacum, nonchlorophyllic cell line SL) and pea (Pisum sativum) roots were investigated. Compared with the control treatment without Al, the accumulation of Al in tobacco cells caused instantaneously the repression of mitochondrial activities [monitored by the reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and the uptake of Rhodamine 123] and, after a lag of about 12 h, triggered reactive oxygen species (ROS) production, respiration inhibition, ATP depletion, and the loss of growth capability almost simultaneously. The presence of an antioxidant, butylated hydroxyanisol, during Al treatment of SL cells prevented not only ROS production but also ATP depletion and the loss of growth capability, suggesting that the Al-triggered ROS production seems to be a cause of ATP depletion and the loss of growth capability. Furthermore, these three late events were similarly repressed in an Al-tolerant cell line (ALT301) isolated from SL cells, suggesting that the acquisition of antioxidant functions mimicking butylated hydroxyanisol can be a mechanism of Al tolerance. In the pea root, Al also triggered ROS production, respiration inhibition, and ATP depletion, which were all correlated with inhibition of root elongation. Taken together, we conclude that Al affects mitochondrial functions, which leads to ROS production, probably the key critical event in Al inhibition of cell growth.

The use of reclaimed water for agricultural irrigation has emerged as a new strategy for coping with water scarcity in semiarid countries. However, the incorporation of the organic microcontaminants in such water into the diet through crop uptake poses a potential risk to human health. This paper aims to assess the presence of organic microcontaminants in different crops irrigated with groundwater and reclaimed water (secondary or tertiary effluents) in a greenhouse experiment. The determination of microcontaminants in water and vegetation samples was performed by solid-phase extraction and matrix solid-phase dispersion procedure with GC–MS/MS, respectively. The presence of nitrates in the groundwater used for irrigation increased biomass production by a higher proportion than the harvest index. The concentration of microcontaminants in lettuce, carrots, and green beans ranged from less than the limit of quantitation to 571 ng g −1 (fresh weight). Tributyl phosphate and butylated hydroxyanisole exhibited the highest concentration levels in crops. The concentration and frequency of detection of microcontaminants were lower in green bean pods than in green bean roots and leaves. Although the concentrations were generally low, the simultaneous presence of a variety of microcontaminants should be taken into consideration when assessing the risk to human health.

Living organisms encounter various perturbations, and response mechanisms to such perturbations are vital for species survival. Defective stress responses are implicated in many human diseases including cancer and neurodegenerative disorders. Phenol derivatives, naturally occurring and synthetic, display beneficial as well as detrimental effects. The phenol derivatives in this study, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), and bisphenol A (BPA), are widely used as food preservatives and industrial chemicals. Conflicting results have been reported regarding their biological activity and correlation with disease development; understanding the molecular basis of phenol action is a key step for addressing issues relevant to human health. This work presents the first comparative genomic analysis of the genetic networks for phenol stress response in an evolutionary context of two divergent yeasts, Schizosaccharomyces pombe and Saccharomyces cerevisiae. Genomic screening of deletion strain libraries of the two yeasts identified genes required for cellular response to phenol stress, which are enriched in human orthologs. Functional analysis of these genes uncovered the major signaling pathways involved. The results provide a global view of the biological events constituting the defense process, including cell cycle arrest, DNA repair, phenol detoxification by V-ATPases, reactive oxygen species alleviation, and endoplasmic reticulum stress relief through ergosterol and the unfolded protein response, revealing novel roles for these cellular pathways.