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Trapping Acrolein by Theophylline/Caffeine and Their Metabolites from Green Tea and Coffee in Mice and Humans
Abstract
Acrolein (ACR) is found exogenously as a widespread environmental pollutant and endogenously, where it is thought to be involved as a pathogenic factor in the progression of many pathological conditions. Eliminating ACR by dietary-active substances has been found to be one potential strategy to prevent ACR-associated chronic diseases. This study first compared the scavenging ACR efficacy of four purine alkaloids, theophylline (TP), paraxanthine (PXT), theobromine (TB), and caffeine (CAF), and then, TP, CAF, and their metabolites were investigated for their ability to trap ACR in vivo. Our results indicated that TP, which possesses an -NH moiety at the N-7 position, exhibits the best ACR-trapping capacity in vitro, while CAF has a slight ability to trap ACR due to the substitutions by -CH3 at the N-1, N-3, and N-7 positions. After oral administration of TP or CAF, the ACR adducts of TP and the metabolites of TP or CAF (e.g., mono- and di-ACR-TP, mono-ACR-1,3-DMU, and mono-ACR-1-MU) were detected in urinary samples obtained from both TP- and CAF-treated mouse groups by using ultra-performance liquid chromatography-tandem mass spectrometry. The quantification studies demonstrated that TP and its metabolites significantly trapped ACR in a dose-dependent manner in vivo. Furthermore, we also detected those ACR adducts of TP and TP/CAF's metabolites in human urine after four cups of green tea (2 g tea leaf/cup) or two cups of coffee (4 g coffee/cup) were consumed per day. Those results indicated that dietary TP or CAF has the potential capacity to scavenge ACR in vivo.
... In particular, edaravone can target the ene and carbonyl groups of acrolein to yield di-adducts [86]. Moreover, caffeine and theophylline [87] can trap acrolein, and their metabolites can continually scavenge acrolein in vivo; these adducts could be detected in the urinary samples of volunteers [88]. In conclusion, although many clinical drugs have shown effective acrolein-scavenging activity in a large amount of studies and have even been clinically applied to avoid acrolein-induced toxic side effects, some studies have indicated that the accumulation of drug-acrolein adducts may trigger new health risks [89]. ...
Acrolein is a highly toxic agent that may promote the occurrence and development of various diseases. Acrolein is pervasive in all kinds of foods, and dietary intake is one of the main routes of human exposure to acrolein. Considering that acrolein is substantially eliminated after its formation during food processing and re-exposed in the human body after ingestion and metabolism, the origin and fate of acrolein must be traced in food. Focusing on molecular mechanisms, this review introduces the formation of acrolein in food and summarises both in vitro and in vivo fates of acrolein based on its interactions with small molecules and biomacromolecules. Future investigation of acrolein from different perspectives is also discussed.
Acrolein (ACR) is a highly reactive α,β-unsaturated aldehyde that plays a key role in the pathogenesis of human diseases, such as atherosclerosis and pulmonary, cardiovascular, and neurodegenerative disorders. We investigated the capture capacity of hesperidin (HES) and synephrine (SYN) on ACR by individual and combined means in vitro, in vivo (utilizing a mouse model), and via a human study. After proving that HES and SYN could efficiently capture ACR by generating ACR adducts in vitro, we further detected the adducts of SYN-2ACR, HES-ACR-1, and hesperetin (HESP)-ACR in mouse urine by ultraperformance liquid chromatography-tandem mass spectrometry. Quantitative assays revealed that adduct formation occurred in a dose-dependent manner, and that there was a synergistic effect of HES and SYN on capturing ACR in vivo. Moreover, quantitative analysis suggested that SYN-2ACR, HES-ACR-1, and HESP-ACR were formed and excreted through the urine of healthy volunteers consuming citrus. The maximum excretions of SYN-2ACR, HES-ACR-1, and HESP-ACR were at 2-4, 8-10, and 10-12 h, respectively, after dosing. Our findings propose a novel strategy for eliminating ACR from the human body via the simultaneous consumption of a flavonoid and an alkaloid.
The objective of this study was to derive food-based dietary guidelines for the Dutch population. The dietary guidelines are based on 29 systematic reviews of English language meta-analyses in PubMed summarizing randomized controlled trials and prospective cohort studies on nutrients, foods and food patterns and the risk of 10 major chronic diseases: coronary heart disease, stroke, heart failure, diabetes, breast cancer, colorectal cancer, lung cancer, chronic obstructive pulmonary disease, dementia and depression. The committee also selected three causal risk factors for cardiovascular diseases or diabetes: systolic blood pressure, low-density lipoprotein cholesterol and body weight. Findings were categorized as strong or weak evidence, inconsistent effects, too little evidence or effect unlikely for experimental and observational data separately. Next, the committee selected only findings with a strong level of evidence for deriving the guidelines. Convincing evidence was based on strong evidence from the experimental data either or not in combination with strong evidence from prospective cohort studies. Plausible evidence was based on strong evidence from prospective cohort studies only. A general guideline to eat a more plant food-based dietary pattern and limit consumption of animal-based food and 15 specific guidelines have been formulated. There are 10 new guidelines on legumes, nuts, meat, dairy produce, cereal products, fats and oils, tea, coffee and sugar-containing beverages. Three guidelines on vegetables, fruits, fish and alcoholic beverages have been sharpened, and the 2006 guideline on salt stayed the same. A separate guideline has been formulated on nutrient supplements. Completely food-based dietary guidelines can be derived in a systematic and transparent way.European Journal of Clinical Nutrition advance online publication, 6 April 2016; doi:10.1038/ejcn.2016.52.
The purposes of this study were to perform a detailed analysis how: i) the frequency of coffee/tea consumption and ii) the use of additives in coffee/tea is associated with measures of total and abdominal obesity.
3,823 participants of the 2003-2004 National Health and Nutrition Examination Survey were examined. Obesity was assessed by BMI and waist circumference (WC). Coffee and tea consumption and use of additives were assessed by questionnaire.
Coffee consumption was not related to BMI or WC in either gender. However, men who drank ≥2 cups of tea per day had lower BMI (25.9 vs. 28.0 kg/m(2)) and WC (95.2 vs. 101.32 cm) values than men who never drank drink tea (p ≤ 0.05). The associations between tea consumption and BMI or WC were no longer significant after adjustment for additive use. Coffee/tea drinkers who used artificial sweeteners had larger (p ≤ 0.05) BMIs than coffee/tea drinkers who did not use sweeteners (28.2 vs. 27.1 kg/m(2) in men, 28.4 vs. 27.1 kg/m(2) in women).
Frequency of coffee/tea consumption was not associated with measures of obesity because additive use explained the association between tea consumption and obesity in men. Artificial sweetener use within coffee/tea was associated with higher BMI.
Many ophthalmologists instruct patients with glaucoma to avoid coffee, although data supporting this practice are insufficient.
To estimate the effect of drinking coffee on intraocular pressure (IOP).
In this crossover study, the effect of the consumption of regular (180 mg caffeine in 200 mL beverage) and decaffeinated coffee (3.6 mg caffeine in 200 mL beverage) was compared in patients with normotensive glaucoma (n = 6) or ocular hypertension (n = 22). IOP was monitored in both groups at 30, 60, and 90 minutes after coffee ingestion.
In patients with normotensive glaucoma who drank regular coffee, the mean +/- SD changes in IOP at 30, 60, and 90 minutes were 0.9 +/- 0.5, 3.6 +/- 1.1, and 2.3 +/- 0.66 mm Hg, respectively; in those who drank decaffeinated coffee, they were 0.75 +/- 0.36, 0.70 +/- 0.4, and 0.4 +/- 0.6 mm Hg, respectively. The corresponding values in patients with ocular hypertension were as follows: after regular coffee, 1.1 +/- 0.7, 3.4 +/- 1.0, and 3.0 +/- 2.7 mm Hg; and after decaffeinated coffee, 0.6 +/- 0.4, 0.9 +/- 0.2, and 0.5 +/- 0.5 mm Hg. The difference in the change in IOP from baseline after ingestion of regular versus decaffeinated coffee was statistically significant in each group at 60 and 90 minutes. Subjects who drank regular coffee demonstrated a greater elevation in IOP; this elevation may be clinically significant.
Intake of caffeinated beverage (>/=180 mg caffeine) may not be recommended for patients with normotensive glaucoma or ocular hypertension.
The influence of gender, exercise, and thermal stress on caffeine pharmacokinetics is unclear. We hypothesized that these factors would not have an effect on the metabolism of caffeine. Eight women participated in four 8-h trials and six men participated in two 8-h trials after the ingestion of 6 mg/kg caffeine. The women performed two resting trials (1 in the follicular phase and 1 in the luteal phase of the menstrual cycle) and two exercise trials (90 min of cycling exercise at 65% of maximal O(2) uptake, 1 h after caffeine ingestion) in the follicular phase (1 without and 1 with an additional thermal stress). The men performed one exercise and one resting trial. Menstrual cycle, gender, and exercise, with or without an additional thermal stress, had no effect on the pharmacokinetic measurements or urine caffeine. There was a trend for higher plasma caffeine and lower plasma paraxanthine concentrations in the women. These results confirm that gender, exercise, and thermal stress have no effect on caffeine pharmacokinetics in men and women.
Increasing evidence has identified the unsaturated aldehyde acrolein (ACR) as the potential factor that causes DNA cross-linking and the development of chronic diseases. The objective of this study was to investigate the mechanism by which theophylline (TP) scavenges ACR for the first time. TP efficiently scavenged ACR through forming adducts, which was demonstrated in a system in which TP was incubated with ACR at different ratios for different times for LC-MS/MS. Then, the mono- and di-ACR-TP adducts were purified, and their structures were elucidated by HRMS and NMR. We found that the ACR residue on mono-ACR-TP further trapped one more ACR and formed di-ACR-TP adducts. Furthermore, mono- and di-ACR-TP had similar time-dependent ACR-scavenging activity as TP. Finally, we demonstrated that green tea, coffee, and cocoa inhibited ACR by trapping ACR to form mono- and di-ACR-TP adducts during the incubation of green tea, coffee, and cocoa with ACR.
Acrolein (ACR) is an unsaturated aldehyde with high activity and toxicity and is produced in vivo and in food. This study investigated the impact of B-ring structure on the trapping of ACR by flavonols and the trapping mechanism and efficacy of ACR by myricetin. Galangin, kaempferol, quercetin, and myricetin, which possess the same A- and C-ring but different numbers of -OH groups on the B-ring, were selected for this study. Our results suggested that increasing the number of -OH groups on the B-ring can enhance the ACR trapping efficacy of flavonol and myrectin was identified as the most active flavonol. The adducts of myricetin with ACR under different ratios and incubation times were analyzed using LC-MS/MS. We also purified and identified the major mono- and di-ACR-myricetin adducts. Furthermore, myricetin could dose-dependently inhibit the formation of ACR in cookies through the formation of mono- and di-ACR adducts.
Scope:
Acrolein is a highly toxic unsaturated aldehyde. Humans are both endogenously and exogenously exposed to acrolein. Long-term exposure to acrolein leads to various chronic diseases. Dietary polyphenols have been reported to be able to attenuate acrolein-induced toxicity in vitro via formation of acrolein-polyphenol conjugates. However, whether in vitro acrolein-trapping abilities of polyphenols can be maintained under in vivo environments is still unknown.
Methods and results:
Two most commonly consumed dietary polyphenols, (-)-epigallocatechin-3-gallate (EGCG) from tea and genistein from soy, were used to evaluate for their anti-acrolein behaviors both in vitro and in mice. Tea EGCG exerted much higher capacity to capture acrolein than soy genistein in vitro. But translation of in vitro anti-acrolein activity into in vivo was mainly mediated by bioavailability and biotransformation of individual polyphenols. We found that 1) both absorbed EGCG and genistein could trap endogenous ACR by forming mono-ACR adducts and eventually be excreted into mouse urine; 2) both absorbed EGCG and genistein could produce active metabolites, MeEGCG and orobol, to scavenge endogenous ACR; 3) both MeEGCG and non-absorbed EGCG showed ability to trap ACR in the gut; 4) considerable amounts of microbial metabolites of genistein displayed enhanced anti-ACR capacity both in the body and in the gut, compared to genistein; and 5) biotransformation of genistein is able to boost its in vivo anti-ACR capacity, compared to EGCG.
Conclusion:
Our findings demonstrate that in vivo anti-acrolein ability of dietary polyphenols cannot be reflected solely based on their in vitro ability. The bioavailability and biotransformation of individual polyphenols especially gut microbiome contribute to in vivo anti-acrolein ability of dietary polyphenols. This article is protected by copyright. All rights reserved.
Background:
Coffee and tea are the most widely consumed beverages worldwide. However, the consumer may be unaware regarding the exact amount of methyl xanthine (MX i.e. caffeine (C), theobromine (TB) and theophylline (TH)) consumed, as majority of the products does not mention the amount. This may lead to serious risks including cardiovascular, kidney and stimulant effects. Aim of the study To determines MX amount in ready to use beverages (coffee and tea) collected from various outlets at the city of Al-Khobar, Saudi Arabia.
Material and methods:
Fourty different samples of espresso, black coffee and red tea were collected. A fast, reliable and efficient UHPLC-DAD method was developed and validated for MX determination. Total lipids were extracted and fractionated in order to determine glycolipids, phospholipids and neutral lipids.
Results:
The r2 value for the method ranged from 0.980-0.988 in a linearity range of 0.5-200 ppm. The range for MX; C (0.02-2.39 mg/mL), TB (0.00-0.10 mg/mL) and TH (0.00-0.004 mg/mL) and total lipids was 1-5 g. Glycolipids (3.1 g) was found higher among the lipid fractions followed by phospholipids (1.8 g) and neutral lipid (0.25 g). In general, espresso beverages (20-30 mL) contained high amount of MX whereas black coffee beverages contained high amount of lipids. Most of the beverages expressed either C, TB, TH, lipids or its fractions however, the products with sound amount of MX and lipids at the same time were; Espresso (Chemistry and Wogard).
Conclusion:
The MX and lipids in these beverages is though quiet below the allowed limits, still care may be taken. Especially when using the beverages with high serving volume (200-250 mL) or coffee prepared via filter method i.e. black coffee, using high temperature for longer time.
Cardiovascular diseases (CVDs) are the leading cause of death worldwide. The majority of cardiovascular complications are secondary to atherosclerosis. Extensive evidence has showed that environmental pollutants such as cigarette smoke and automobile exhaust increase the risk of developing atherosclerosis. Acrolein, a highly reactive unsaturated aldehyde, is found as a contaminant in air, food and water. Investigations during the last decades have shown that acrolein via various mechanisms such as oxidative stress, enhancement of inflammatory processes and the activation of matrix metalloproteases can initiate and accelerate atherosclerotic lesions formation. Furthermore, exposure to acrolein has been suggested to induce or exacerbate systemic dyslipidemia, an important risk factor for the development of atherosclerosis. Finally, there are reports which indicate acrolein can increase platelet activation and stimulation of the coagulation cascade which subsequently leads to thrombosis. Even a modest reduction of pollutants such as acrolein can have substantial effects on population health. Public health efforts to reduce acrolein exposures from known sources may lower the prevalence of vascular disease. This review focuses on the potential pathways and mechanisms behind the acrolein-induced atherothrombotic effects.
The in vivo mechanism of tea polyphenol-mediated prevention of many chronic diseases is still largely unknown. Studies have shown that accumulation of toxic reactive cellular metabolites, such as ammonia and reactive carbonyl species (RCS), is one of the causing factors to the development of many chronic diseases. In this study, we investigated the in vivo interaction between (-)-epigallocatechin-3-gallate (EGCG), the most abundant polyphenol in tea leaves, and ammonia and RCS. We found that EGCG could be oxidized to EGCG quinone in mice, and then rapidly react with ammonia to generate the aminated EGCG metabolite, 4′-NH2-EGCG. Both EGCG and its aminated metabolite could further scavenge RCS, such as methylglyoxal (MGO), malondialdehyde (MDA), and trans-4-hydroxy-2-nonenal (4-HNE), to produce the RCS conjugates of EGCG and the aminated EGCG. Both the aminated and the RCS conjugated metabolites of EGCG were detected in human after drinking four cups of green tea per day. By comparing the levels of the aminated and the RCS conjugated metabolites in EGCG exposed germ-free (GF) mice and specific-pathogen-free (SPF) mice, we demonstrated that gut microbiota facilitate the formation of the aminated metabolite of EGCG, the RCS conjugates of EGCG, and the RCS conjugates of the aminated EGCG. By comparing the trapping capacities of EGCG and its aminated metabolite under aerobic and anaerobic conditions, we found that oxygen is not essential for the trapping of reactive species by EGCG and 4′-NH2-EGCG suggesting that EGCG and its aminated metabolite could scavenge RCS in the GI track and in the circulation system. Altogether, this study provides in vivo evidences that EGCG has the capacity to scavenge toxic reactive metabolic wastes. This finding opens a new window to understand the underlying mechanisms by which drinking tea could prevent the development of chronic diseases.
Background and aim: Here, we examined the potential effect of coffee consumption and total caffeine intake on the occurrence of pre-diabetes and T2D, in a population with low coffee consumption. Methods and Results: Adults men and women, aged 20–70 years, were followed for a median of 5.8 y. Dietary intakes of coffee and caffeine were estimated using a 168-food items validate semi-quantitative food frequency questionnaire, at baseline. Cox proportional hazards regression models, adjusted for potential cofounders, were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between coffee and caffeine intakes and incidence of pre-diabetes and T2D. The total population was 1878 adults (844 men, 1034 women) and 2139 adults (971 men, 1168 women) for analysis of pre-diabetes and T2D, respectively. During the follow-up period the incidence of pre-diabetes and T2D was 30.8% and 6.6%, respectively. Forty-three percent of our subjects were no coffee drinker whereas 51.4% consumed 1 cup of coffee/week and 6.0% consumed more than 1 cup of coffee/week. A lower risk of pre-diabetes (HR = 0.73, 95% CI = 0.62–0.86) and T2D (HR = 0.66, 95% CI = 0.44–1.00) was observed in coffee drinkers compared to non-drinkers, in the fully adjusted models. Higher dietary intake of caffeine (≥152 vs. <65 mg/d) was accompanied with a borderline (P = 0.053) reduced risk of pre-diabetes (HR = 0.45, 95% CI = 0.19–1.00). Conclusion: Our findings indicated that coffee drinking may have favorable effect in prevention of pre-diabetes and T2D. © 2018 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University
Caffeine is the most widely used psychostimulant in Western countries, with antioxidant, anti-inflammatory and anti-apoptotic properties. In Alzheimer's disease (AD), caffeine is beneficial in both men and women, in humans and animals. Similar effects of caffeine were observed in men with Parkinson's disease (PD); however, the effect of caffeine in female PD patients is controversial due to caffeine's competition with estrogen for the estrogen-metabolizing enzyme, CYP1A2. Studies conducted in animal models of amyotrophic lateral sclerosis (ALS) showed protective effects of A2AR antagonism. A study found caffeine to be associated with earlier age of onset of Huntington's disease (HD) at intakes >190 mg/d, but studies in animal models have found equivocal results. Caffeine is protective in AD and PD at dosages equivalent to 3-5 mg/kg. However, further research is needed to investigate the effects of caffeine on PD in women. As well, the effects of caffeine in ALS, HD and Machado-Joseph disease need to be further investigated. Caffeine's most salient mechanisms of action relevant to neurodegenerative diseases need to be further explored.
Methylxanthines (MTXs) are consumed by almost everybody in almost every area of the world. Caffeine, theophylline and theobromine are the most well-known members of this family of compounds; they are present, inter alia, in coffee, tea, cacao, yerba mate and cola drinks. MTXs are readily absorbed in the gastrointestinal tract and are able to penetrate into the central nervous system, where they exert significant psychostimulant actions, which are more evident in acute intake. Coffee has been paradigmatic, as its use was forbidden in many diseases, however, this negative view has radically changed; evidence shows that methylxanthines display health benefits in diseases involving cell death in the nervous system. This paper reviews data that appraise the preventive and even therapeutic potential of MTXs in a variety of neurodegenerative diseases. Future perspectives include the use of MTXs to advance the understanding the pathophysiology of, inter alia, Alzheimer's disease (AD) and Parkinson's disease (PD), and the use of the methylxanthine chemical moiety as a basis for the development of new and more efficacious drugs. Abstract Neuroprotective effects of methylxanthines and xanthine-based drugs. A) The long-term moderate methylxanthine consumption seems protective against accumulation of noxious events that result in age-linked neurodegenerative diseases. B) Once the neurodegenerative process has been established, xanthine derived-drugs appear as effective tools for therapy.
Obesity is a serious health problem in adults and children worldwide. However, the basic strategies for the management of obesity (diet, exercise, drugs and surgery) have limitations and side effects. Therefore, many researchers have sought to identify bioactive components in food. Tea and coffee are the most frequently consumed beverages in the whole world. Their health benefits have been studied for decades, especially those of green tea. The anti-obesity effect of tea and coffee has been studied for at least ten years. The results have shown decreased lipid accumulation in cells via the regulation of the cell cycle during adipogenesis, changes in transcription factors and lipogenesis-related proteins in the adipose tissue of animal models, and decreased body weight and visceral fat in humans. Tea and coffee also influence the gut microbiota in obese animals and humans. Although the anti-obesity mechanism of tea and coffee still needs further clarification, they may have potential as a new strategy to prevent or treat obesity.
The US Departments of Health and Human Services (DHHS) and Agriculture (USDA) have released the eighth edition (2015-2020) of the Dietary Guidelines for Americans.¹ The Dietary Guidelines are an important part of a complex and multifaceted solution to promoting health and preventing diet-related chronic diseases including cardiovascular disease, type 2 diabetes, some cancers, and obesity. The Dietary Guidelines are required under the National Nutrition Monitoring and Related Research Act of 1990 and inform the development of federal food, nutrition, and health policies and programs. They serve as the evidence-based foundation for federal government nutrition education materials and are used to inform programs like Older Americans Act Nutrition Services Programs and the Supplemental Nutrition Assistance Program (SNAP) that affect millions of people each day. The Dietary Guidelines can also be adapted by health care professionals to describe and recommend healthy eating to patients. Recent studies have shown that diets that align closely with the Dietary Guidelines are associated with a significant reduction in the onset of and deaths due to diet-related chronic diseases.²,3
HighlightsAcrolein/crotonaldehyde causes DNA adducts and interstrand cross-links.Epigallocatechin gallate (EGCG) traps acrolein/crotonaldehyde.ECCG lowers DNA adduct formation and interstrand cross-links.AbstractThe present work explored the potential application of phytochemicals in the prevention of DNA adduct formation and interstrand cross-links (ICLs) caused by acrolein (ACR) and crotonaldehyde (CRO). Our study showed that epigallocatechin gallate, a major phenolic compound in green tea, was the most effective compound to prevent DNA adduct formation caused by ACR and CRO and trap ACR and CRO in a chemical system. As an example, epigallocatechin gallate showed the inhibitory effect on dG damage caused by ACR (67.1%) and the best trapping ability against ACR (100%) at the concentration of 10 mM, significantly different from the control without the addition of a phytochemical (P < 0.01). Furthermore, ethidium bromide assay showed that epigallocatechin gallate and caffeine are effective in preventing the formation of ICLs in calf thymus DNA caused by ACR and CRO. Our present work enriches the knowledge base of polyphenols and caffeine for their protective activities toward genomic DNA.Practical ApplicationsDietary phytochemicals in teas, fruits and vegetables offer a vast range of health benefits and possible disease preventive potential to humans. However, little is known whether dietary phytochemicals, particularly polyphenols, can prevent DNA damage or not. Our study suggested that two important phytochemicals in green tea, epigallocatechin gallate and caffeine in tea, can prevent DNA adduct formation and interstrand cross-links induced by lipid peroxidation-related reactive carbonyl species. This information can be incorporated in our daily life for general health management.
Twenty eight coffee samples from around the world were tested for caffeine levels to develop near infrared reflectance spectroscopy (NIRS) calibrations for whole and ground coffee. Twenty-five individual beans from five of those coffees were used to develop a NIRS calibration for caffeine concentration in single beans. We used an international standard high performance liquid chromatography method to analyse for caffeine content. Coffee is a legal stimulant and possesses a number of heath properties. However, there is variation in the level of caffeine in brewed coffee and other caffeinated beverages. Being able to sort beans based on caffeine concentration will improve quality control in the level of caffeine in those beverages. There was a range in caffeine concentration was from 0.01 mg/g (decaffeinated coffee) up to 19.9 mg/g (Italian coffee). The majority of coffees were around 10.0 mg/g to 12.0 mg/g. The NIRS results showed r2 values for bulk unground and ground coffees were greater than 0.90 with standard errors less than 2 mg/g. For the single bean calibration the r2 were between 0.85 and 0.93 with standard errors of cross validation of 0.8 to 1.6 mg/g depending upon calibration. The results showed it was possible to develop NIRS calibrations to estimate the caffeine concentration of individual coffee beans. One application of this calibration could be sorting beans on caffeine concentration to provide greater quality control for high-end markets. Further, bean sorting may open new markets for novel coffee products.
α,β-Unsaturated aliphatic carbonyl compounds are naturally widespread in food, but are also formed during the thermal treatment of food. This applies, for example, to the genotoxic carcinogen acrylamide (AA), but also to acrolein (AC), the simplest α,β-unsaturated aldehyde. First observations indicate that human exposure to AC may be higher than the exposure to AA. The DFG Senate Commission on Food Safety therefore compared data on AC and AA available in the scientific literature, evaluating current knowledge on formation, occurrence, exposure, metabolism, biological effects, toxicity, and carcinogenicity and defined knowledge gaps as well as research needs in an opinion on November 19, 2012, in German. The English version was agreed on April 17, 2013.
Acrolein is an α,β-unsaturated aldehyde formed by thermal treatment of animal and vegetable fats, carbohydrates and amino acids. In addition it is generated endogenously. As an electrophile, acrolein forms adducts with gluthathione and other cellular components and is therefore cytotoxic. Mutagenicity was shown in some in vitro tests. Acrolein forms different DNA adducts in vivo, but mutagenic and cancerogenous effects have not been demonstrated for oral exposure. In subchronic oral studies, local lesions were detected in the stomach of rats. Systemic effects have not been reported from basic studies. A WHO working group established a tolerable oral acrolein intake of 7.5 μg/kg body weight/day. Acrolein exposure via food cannot be assessed due to analytical difficulties and the lack of reliable content measurements. Human biomonitoring of an acrolein urinary metabolite allows rough estimates of acrolein exposure in the range of a few μg/kg body weight/day. High exposure could be ten times higher after the consumption of certain foods. Although the estimation of the dietary acrolein exposure is associated with uncertainties, it is concluded that a health risk seems to be unlikely.
Acrolein (ACR) is a toxic and highly reactive α,β-unsaturated aldehyde widely distributed in the environment as a common pollutant and generated endogenously mainly by lipoxidation reactions. Its biological effects are due to its ability to react with the nucleophilic sites of proteins, to form covalently modified biomolecules which are thought to be involved as pathogenic factors in the onset and progression of many pathological conditions such as cardiovascular and neurodegenerative diseases. Functional impairment of structural proteins and enzymes by covalent modification (crosslinking) and triggering of key cell signalling systems are now well-recognized signs of cell and tissue damage induced by reactive carbonyl species (RCS). In this review, we mainly focus on the in vitro and in vivo evidence demonstrating the ability of ACR to covalently modify protein structures, in order to gain a deeper insight into the dysregulation of cellular and metabolic pathways caused by such modifications. In addition, by considering RCS and RCS-modified proteins as drug targets, this survey will provide an overview on the newly developed molecules specifically tested for direct or indirect ACR scavenging, and the more significant studies performed in the last years attesting the efficacy of compounds already recognized as promising aldehyde-sequestering agents.
Tea and coffee, the most popular beverages in the world, have been consumed for thousands of years for their alluring flavors and health benefits. Polyphenols, particularly flavonoids and phenolic acids, are of great abundance in tea and coffee and contribute a lot to their flavor and health properties. This paper reviews the polyphenol chemistry of tea and coffee, specifically their stability, and scavenging ability of reactive oxygen species (ROS) and reactive carbonyl species (RCS). During the manufacturing and brewing process, green tea and black tea polyphenols undergo epimerization and oxidation, respectively. Meanwhile, the lactonization and the polymerization of chlorogenic acid are the major causes for the degradation of polyphenols in coffee. Tea catechins, besides having antioxidant properties, have the novel characteristic of trapping reactive carbonyl species. The A ring of the catechins is the binding site for RCS trapping, whereas the B ring is the preferred site for antioxidation.
The toxicity of the ubiquitous pollutant and endogenous metabolite, acrolein, is due in part to covalent protein modifications. Acrolein reacts readily with protein nucleophiles via Michael addition and Schiff base formation. Potential acrolein targets in protein include the nucleophilic side chains of cysteine, histidine, and lysine residues as well as the free amino terminus of proteins. Although cysteine is the most acrolein-reactive residue, cysteine-acrolein adducts are difficult to identify in vitro and in vivo. In this study, model peptides with cysteine, lysine, and histidine residues were used to examine the reactivity of acrolein. Results from these experiments show that acrolein reacts rapidly with cysteine residues through Michael addition to form M+56 Da adducts. These M+56 adducts are, however, not stable, even though spontaneous dissociation of the adduct is slow. Further studies demonstrated that when acrolein and model peptides are incubated at physiological pH and temperature, the M+56 adducts decreased gradually accompanied by the increase of M+38 adducts, which are formed from intramolecular Schiff base formation. Adduct formation with the side chains of other amino acid residues (lysine and histidine) was much slower than cysteine and required higher acrolein concentration. When cysteine residues were blocked by reaction with iodoacetamide and higher concentrations of acrolein were used, adducts of the N-terminal amino group or histidyl residues were formed, but lysine adducts were not detected. Collectively, these data demonstrate that acrolein reacts avidly with protein cysteine residues and that the apparent loss of protein-acrolein Michael adducts over time may be related to the appearance of a novel (M+38) adduct. These findings may be important in identification of in vivo adducts of acrolein with protein cysteine residues.
The metabolism and disposition of [2,3-14C]acrolein was studied in Sprague-Dawley rats after oral or intravenous dosing. Four groups of ten rats (five male and five female) were dosed with radiolabeled acrolein intravenously at 2.5 mg kg-1 (Group 2), orally by gavage at 2.5 mg kg-1, either as a single dose (Group 3) or after 14 daily doses of unlabeled acrolein (Group 4), or orally by gavage at 15 mg kg-1 (Group 5). Urine, feces, expired air and organic volatiles were collected for 7 days, after which the animals were sacrificed and tissues collected. All samples were analyzed for total radioactivity. After 7 days, the excretory patterns of male and female rats were almost identical. Urinary excretion was highest in the intravenously dosed animals (66-69%) and lowest in the Group 5 animals (36-40%), whereas the reverse was true for feces (< 2% for i.v. Group 2 animals and 28-30% for the Group 5 animals). Carbon dioxide expiration was comparable (26-31%) across all groups. Tissue concentrations of radioactivity were minimal in all groups (< 1.2%), but concentrations of radioactivity were highest in the intravenous Group 2 animals. The time course of excretion for all groups was similar with the exception of the high-dose animal group, which showed a pronounced delay in excretion during the first 12 h.
The native occurrence of tea polyphenols, namely, (-)-epicatechin, (+)-catechin, (-)-epigallocatechin 3-gallate, (-)-epicatechin, and (-)-epicatechin 3-gallate, and caffeine in tea flowers was assessed by an isocratic HPLC procedure. The levels of total catechins and caffeine were determined in tea flowers collected from 10 different species of Camellia sinensis. The results showed the levels of total catechin ranged from 10 to 38 mg/g, whereas the level of caffeine ranged from 3 to 8 mg/g. Levels of catechins and caffeine in tea leaves and various teas were also determined and ranged from 2 to 126 mg/g and from 23 to 49 mg/g, respectively. Both tea flower and tea leaf extracts exert their strong hydroxyl radical scavenging effects in the Fenton reaction system and nitric oxide suppressing effects in LPS-induced RAW 264.7 cells. Most tea flowers contain less caffeine, but comparable amounts of total catechins, compared to tea leaves and teas. The present study demonstrates that both tea flowers and tea leaves contain appreciable amounts of catechins and caffeine. It is likely that tea flowers might be useful for making alternative tea beverages.
Theanine, caffeine, and catechins in fresh tea leaves and oolong tea were determined by using capillary electrophoresis (CE). CE separated these tea polyphenols from three other tea ingredients, namely, caffeine, theophylline, and theanine, within 8 min. The young leaves (apical bud and the two youngest leaves) were found to be richer in caffeine, (-)-epigallocatechin gallate (EGCg), and (-)-epicatechin gallate (ECg) than old leaves (from 5th to 7th leaves). On the other hand, the old leaves (from 8th to 10th leaves) contained higher levels of theanine, (-)-epigallocatechin (EGC), and (-)-epicatechin (EC). Results from a comparison of fresh young tea and oolong tea compositions indicated oolong tea contained more theanine and catechins than fresh young tea. Furthermore, it was found that the levels of theanine, EGC, and EGCg in young leaves rose markedly with the withering process. Caffeine did not markedly change. However, fully or partially fermented teas (oolong tea or pauchong tea) have a common initial step in the withering process. Fresh tea leaves or oolong tea extract (0.1%, w/v) markedly inhibited neurosphere adhesion, cell migration, and neurite outgrowth in rat neurospheres. Theanine (348 micrograms/mL) and caffeine at high concentration (50 micrograms/mL) did not inhibit neurosphere adhesion or migration activities, but EGCg at 20 micrograms/mL effectively inhibited neurosphere adhesion for 24 h. These results indicated that EGCg might affect neural stem cell survival or differentiation.
Acrolein, an alpha,beta-unsaturated aldehyde, is a ubiquitous environmental toxic pollutant. Because of potential human exposure, there is a need for a sensitive, reliable, and specific method to monitor acrolein exposure. Acrolein is a potent electrophile and reacts with proteins mainly through Michael addition reaction, leading to acrolein-protein adducts (APA). The present study aimed to develop a competitive enzyme-linked immunosorbent assay (ELISA) method for the quantitation of APA in biological samples. Antibody to acrolein-keyhole limpet hemocyanin adduct was raised in rabbits, and the specificity of the antibody was determined by ELISA using acrolein-albumin adduct (AAA) or native albumin. A dose-dependent response was observed with AAA, but no immunoreactivity with native albumin. Further, lack of cross-reactivity of anti-acrolein antibody with formaldehyde-, malondialdehyde-, or 4-hydroxynonenal-albumin adducts indicates its specificity for acrolein. For the competitive ELISA, 1:16,000 diluted antisera was used with varying concentrations of AAA, which provided a linear detection range between 250 and 10,000 pg. To test the efficacy of the method for possible use as a biomarker of acrolein exposure, SD rats were orally administered 1 or 7 doses of 9.2 mg/kg/d acrolein. APA levels, quantitated in the serum, showed significantly greater formation (32% and 58% after 1 and 7 doses, respectively) in acrolein-treated rats as compared to the controls. Western blot analyses of APA in the sera from acrolein-treated rats showed APA bands (especially 29, 31, and 100 kD) with greater intensity in comparison to controls, further supporting our ELISA results. These results suggest that quantitation of APA has potential to be used as biomarker of acrolein exposure and eventually for molecular dosimetry and risk assessment.
The aim of this study was to test the usefulness of the metabolite/caffeine ratio for the evaluation of hepatic dysfunction. Subjects with liver cirrhosis and chronic hepatitis, as well as healthy volunteers, were given the oral dose of 300 mg caffeine. Blood samples were collected after 4, 8, and 12 hours. Concentrations of caffeine (CA) and its three metabolites-paraxanthine (PX), theobromine (TB), and theophylline (TP)-were determined by high-performance liquid chromatography. Pharmacokinetic parameters of caffeine and PX/CA, TB/CA, and TP/CA ratios were calculated. Elimination of caffeine was decreased in cirrhotics in comparison with healthy volunteers, as proved by the values of clearance (0.035 vs. 0.094 L/h/kg), elimination coefficient (0.061 vs. 0.153 h(-1)), and half-life (11.4 vs. 4.3 h). Serum metabolite/caffeine ratios were significantly reduced in cirrhotic patients: PX/CA by more than 80%, TB/CA by 50% to 70%, and TP/CA by 40% to 70%. The reduction of the ratios in chronic hepatitis patients was lower and did not occur at all time points. A high correlation was found between caffeine clearance and metabolite/caffeine ratios. Metabolite/caffeine ratios calculated in a single blood sample collected 8 or 12 hours after caffeine administration could provide a practical assessment of hepatic function in cirrhotic patients. The value of the test for the chronic hepatitis patients is limited.
Acrolein (2-propenal) is ubiquitously present in (cooked) foods and in the environment. It is formed from carbohydrates, vegetable oils and animal fats, amino acids during heating of foods, and by combustion of petroleum fuels and biodiesel. Chemical reactions responsible for release of acrolein include heat-induced dehydration of glycerol, retro-aldol cleavage of dehydrated carbohydrates, lipid peroxidation of polyunsaturated fatty acids, and Strecker degradation of methionine and threonine. Smoking of tobacco products equals or exceeds the total human exposure to acrolein from all other sources. The main endogenous sources of acrolein are myeloperoxidase-mediated degradation of threonine and amine oxidase-mediated degradation of spermine and spermidine, which may constitute a significant source of acrolein in situations of oxidative stress and inflammation. Acrolein is metabolized by conjugation with glutathione and excreted in the urine as mercapturic acid metabolites. Acrolein forms Michael adducts with ascorbic acid in vitro, but the biological relevance of this reaction is not clear. The biological effects of acrolein are a consequence of its reactivity towards biological nucleophiles such as guanine in DNA and cysteine, lysine, histidine, and arginine residues in critical regions of nuclear factors, proteases, and other proteins. Acrolein adduction disrupts the function of these biomacromolecules which may result in mutations, altered gene transcription, and modulation of apoptosis.