Heterocyclic Aromatic Amines Research Articles

Short-Term Exposure to 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine Induces Colonic Energy Metabolism Disorders in Rats.

2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is one of the most abundant heterocyclic aromatic amines generated in thermally processed meat products, and the toxicities of its short-term exposure in the intestines remain unclear. This study aimed to elucidate the short-term PhIP toxicity in colons through administering PhIP orally to rats for 4 weeks. The results indicated that short-term PhIP exposure induced colonic oxidative stress, a significant decrease of serum triglyceride, and a disrupted colonic gene expression pattern associated with mitochondrial electron transport chain and energy metabolism. Thirteen energy metabolites, including lactate and d-erythrose-4-phosphate, showed significant changes under short-term PhIP effects. Energy metabolism pathway analysis revealed that PhIP-induced colonic energy metabolism disorders are characterized by inhibited glycolysis and enhanced tricarboxylic acid cycle. Further investigation found that PhIP altered the energy metabolic phenotype of colon epithelial cells to increase aerobic respiration. In summary, our study provides new insights into the colon toxicity induced by a short-term PhIP exposure.

Plasma-activated water pretreatment as a promising technique to reduce the formation of heterocyclic aromatic amines and advanced glycation end products in roasted fish patties

This study investigated the efficacy of using plasma-activated water (PAW) as a novel and additive-free pretreatment in reducing the formation of free and bound heterocyclic aromatic amines (HAAs) and advanced glycation end products (AGEs) in roasted fish patties. PAW activated for different durations (50 s, 100 s, and 150 s), significantly decreased the levels of HAAs and AGEs. The highest inhibition rates were observed at 35.44% and 19.82% for free and bound HAAs, respectively, and 42.76% and 23.23% for free and bound AGEs, respectively. PAW pretreatment reduced the formation of HAAs and AGEs and mitigated their increase during storage. Analysis using electron paramagnetic resonance and UPLC-MS/MS showed a decrease in free radicals and reactive carbonyls (phenylglyoxal, glyoxal, and methylglyoxal), which can serve as intermediates for HAAs and AGEs. Correlation analysis indicated a significant positive correlation between HAAs/AGEs and phenylacetaldehyde, glyoxal, methylglyoxal, and the total spin number (P < 0.05). This suggests that PAW suppresses the production of reactive carbonyls by quenching free radicals, thereby inhibiting the formation of HAAs and AGEs. In conclusion, with its additive-free approach, PAW pretreatment holds promise for reducing HAAs and AGEs and improving the safety of roasted fish products.

A green deep eutectic solvent-based aqueous two-phase system for the extraction of heterocyclic aromatic amines from marinating juice

A green deep eutectic solvent-based aqueous two-phase system for the extraction of heterocyclic aromatic amines from marinating juice

Comparing effects of tangerine-peel (Citrus reticulata Blanco) age and concentration on deep-fried rabbit meat: Impact on heterocyclic aromatic amines, amino acids, and flavor compound formation

Many nutritional experts recommend rabbit meat as a high-protein source. However, the high temperatures used to prepare deep-fried rabbit meat (DFRM) typically produce numerous heterocyclic aromatic amines (HAAs), a class of substances with carcinogenic risks. In this study, we chromatographically evaluate changes in the volatile compounds, amino acids, and HAAs in DFRM while employing tangerine peel (TP) as an additive. A total of 35 volatile organic compounds are detected in the TP, which increase the concentrations of sweet and umami amino acids in the DFRM. Remarkably, the TP substantially inhibits the IQ-type HAAs, particularly MeIQ, MeIQx, 4,8-DiMeIQx, and PhIP, which are produced during deep frying. Correlation analyses reveal that the histidine, aldehydes, and alcohols are strongly and positively correlated (P < 0.001) with the MeIQ, MeIQx, 4,8-DiMeIQx, and PhIP production. This study offers innovative and natural approaches for reducing HAA formation during the frying of rabbit meat.

Exploration of the prediction and generation patterns of heterocyclic aromatic amines in roast beef based on Genetic Algorithm combined with Support Vector Regression

Heterocyclic aromatic amines (HAAs) are harmful byproducts in food heating. Therefore, exploring the prediction and generation patterns of HAAs is of great significance. In this study, genetic algorithm (GA) and support vector regression (SVR) are used to establish a prediction model of HAAs based on heating conditions, reveal the influence of heating temperature and time on the precursor and formation of HAAs in roast beef, and study the formation rules of HAAs under different processing conditions. Principal component analysis (PCA) showed that the effect on HAAs generation increases with the increase of heating temperature and time. The GA-SVR model exhibited near-zero absolute errors and regression correlation coefficients (R) close to 1 when predicting HAAs contents. The GA-SVR model can be applied for real-time monitoring of HAAs in grilled beef, providing technical support for controlling hazardous substances and intelligent processing of heat-processed meat products.

Comparative analysis of free and bound heterocyclic aromatic amines in fried chicken drumsticks affected by various vegetable oils

The study explored the impact of different vegetable oils, including soybean oil, rice bran oil, and safflower oil, on the generation of free and protein-bound heterocyclic aromatic amines (HAAs) in fried chicken drumsticks. All fried samples showed increased pH values, a*-values (the redness), and b*-values (the yellowness), while decreased L*-values (the brightness) and water content than the control sample (P < 0.05). Fried chicken drumsticks contained a total of 10 HAAs, including five types of free HAAs (MeIQ, MeIQx, PhIP, Harman, and Norharman), as well as five types of protein-bound HAAs (4,8-DiMeIQx, 7,8-DiMeIQx, AαC, Harman, and Norharman). Drumsticks prepared with safflower oil exhibited the highest levels of free HAAs (248.23 ng/g) and protein-bound HAAs (116.14 ng/g). In contrast, those fried in rice bran oil showed the lowest levels of free HAAs (172.92 ng/g) and protein-bound HAAs (99.13 ng/g) (P < 0.05). In conclusion, rice bran oil is an appropriate choice for frying chicken drumsticks due to its ability to reduce HAAs, which provides a scientific foundation for the production of fried chicken drumsticks.

Using bioactive compounds to mitigate the formation of typical chemical contaminants generated during the thermal processing of different food matrices.

With rising consumer awareness of health and wellness, the demand for enhanced food safety is rapidly increasing. The generation of chemical contaminants during the thermal processing of food materials, including polycyclic aromatic hydrocarbons, heterocyclic aromatic amines, and acrylamide happens every day in every kitchen all around the world. Unlike extraneous chemical contaminants (e.g., pesticides, herbicides, and chemical fertilizers), these endogenic chemical contaminants occur during the cooking process and cannot be removed before consumption. Therefore, much effort has been invested in searching for ways to reduce such thermally induced chemical contaminants. Recently, the addition of bioactive compounds has been found to be effective and promising. However, no systematic review of this practical science has been made yet. This review aims to summarize the latest applications of bioactive compounds for the control of chemical contaminants during food thermal processing. The underlying generation mechanisms and the toxic effects of these chemical contaminants are discussed in depth to reveal how and why they are suppressed by the addition of certain bioactive ingredients. Examples of specific bioactive compounds, such as phenolic compounds and organic acids, as well as their application scenarios, are outlined. In the end, outlooks and expectations for future development are provided based on a comprehensive summary and reflection of references.

A magnetic carboxyl-functionalized covalent organic framework for the efficient enrichment of foodborne heterocyclic aromatic amines prior to UPLC-MS analysis

Foodborne heterocyclic aromatic amines (HAAs) are potent mutagens and carcinogens, posing significant health risks. Existing enrichment methods for HAAs need better adsorption selectivity and capacity for daily exposure assessment. This study hypothesized that introducing carboxylic groups into magnetic covalent organic frameworks (m-COFs) would improve HAAs adsorption by providing additional binding sites. Hence, we prepared a novel magnetic adsorbent, termed as Fe3O4@DOPA-TpPa-(COOH)2 capable of enhancing the HAAs detection through magnetic solid-phase extraction (MSPE) coupled with UPLC-MS. This sorbent demonstrated a large specific surface area (130.7 m2/g), high magnetic responsivity (21.05 emu/g), and robust stability, with an adsorption capacity (Qm[cal]: 81.82 mg/g) driven by electrostatic, LP − π/C-H − π interactions, and hydrogen bonding. Optimal MSPE conditions provided sensitive detection with a broad linear range (5–500 ng/mL), low limits of detection (0.01–7.01 ng/g), and excellent repeatability. Application to Cantonese mooncake samples showed satisfactory recoveries (62.12%–126.86%). This method offers a more accurate tool for detecting HAAs.

Food process contaminants: formation, occurrence, risk assessment and mitigation strategies - a review.

Thermal treatment of food can lead to the formation of potentially harmful chemicals, known as process contaminants. These are adventitious contaminants that are formed in food during processing and preparation. Various food processing techniques, such as heating, drying, grilling, and fermentation, can generate hazardous chemicals such as acrylamide (AA), advanced glycation end products (AGEs), heterocyclic aromatic amines (HAAs), furan, polycyclic aromatic hydrocarbons (PAHs), N-nitroso compounds (NOCs), monochloropropane diols (MCPD) and their esters (MCPDE) which can be detrimental to human health. Despite efforts to prevent the formation of these compounds during processing, eliminating them is often challenging due to their unknown formation mechanisms. It is critical to identify the potential harm to human health in processed food and understand the mechanisms by which harmful compounds form during processing, as prolonged exposure to these toxic compounds can lead to health problems. Various mitigation strategies, such as the use of diverse pre- and post-processing treatments, product reformulation, additives, variable process conditions, and novel integrated processing techniques, have been proposed to control these food hazards. In this review, we summarize the formation and occurrence, the potential for harm to human health produced by process contaminants in food, and potential mitigation strategies to minimize their impact.

Effect of air-frying on formation and correlations of polycyclic aromatic hydrocarbons, acrylamide, and heterocyclic aromatic amines in foods and risk assessment.

The online version contains supplementary material available at 10.1007/s10068-024-01639-4.

A review of heterocyclic aromatic amines in cooked meat: generation pathways and mitigation mechanism by natural exogenous additives

A review of heterocyclic aromatic amines in cooked meat: generation pathways and mitigation mechanism by natural exogenous additives

Simultaneous mitigation of heterocyclic aromatic amines and advanced glycation end products in roasted beef patties by plasma-activated water: Effects and mechanisms

Heterocyclic aromatic amines (HAAs) and advanced glycation end products (AGEs) are hazardous substances produced when food is heated. In this study, the ability of plasma-activated water (PAW) to simultaneously mitigate production of HAAs and AGEs in roasted beef patties was investigated. Assays of free radicals, lipid peroxidation, and active carbonyls were used to analyze the mechanisms. PAW treatment decreased the contents of free HAAs, free AGEs, bound HAAs, and bound AGEs to 12.65 ng/g, 0.10 μg/g, 297.74 ng/g, and 4.32 μg/g, with the inhibition rates of 23.88%, 23.08%, 11.02%, and 8.47%, respectively. PAW treatment decreased HAAs and AGEs and mitigated their increase during storage. The decrease of HAAs and AGEs in PAW-treated samples was correlated with the enhancement of antioxidant capacity. The increase of free radical scavenging ability by PAW treatment led to the decrease of lipid peroxidation and the decrease of active carbonyls, HAAs, and AGEs in meat products.

The magnetic layered double hydroxide/zeolitic imidazolate framework-8 nanocomposite coupled with HPLC-MS/MS for the detection of heterocyclic aromatic amines in thermally processed meat

In this research, a novel magnetic nanocomposite (Fe3O4@Zn/Al-LABSA-LDH/ZIF-8) was synthesized using Fe3O4 as the magnetic core, layered double hydroxide (LDH) with linear alkylbenzene sulfonic acid (LABSA) intercalation and zeolitic imidazolate framework-8 (ZIF-8) as the shell. Benefiting from the intercalation of LABSA into LDH combined with ZIF-8, the multiple interactions, including π-π stacking, hydrogen bonding, and electrostatic interactions, conferred high selectivity and good extraction capability to the material towards heterocyclic aromatic amines (HAAs). Fe3O4@Zn/Al-LABSA-LDH@ZIF-8 was used as an adsorbent for magnetic solid-phase extraction (MSPE) to enrich HAAs in thermally processed meat samples, followed by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) detection. The method exhibited a low detection limit (0.021–0.221 ng/g), good linearity (R2 ≥ 0.9999), high precision (RSD < 7.2 %), and satisfactory sample recovery (89.7 % -107.5 %). This research provides a promising approach for developing novel adsorbents in sample preparation and improving analytical performance.

Effect of free and bound proanthocyanidins from Chinese quince on heterocyclic aromatic amine formation and quality in fried chicken.

The abilities of Chinese quince free proanthocyanidins (FP) and bound proanthocyanidins (BP) at different levels (0.1%, 0.15%, and 0.3%) to mitigate heterocyclic aromatic amine (HAA) formation in fried chicken patties were investigated for the first time and compared with vitamin C (Vc). FP and BP reduced HAAs in a dose-dependent manner. Significantly, high concentrations of FP (0.3%) resulted in a reduction of PhIP, harman, and norharman levels by 59.84%, 22.91%, and 38.21%, respectively, in chicken patties. The addition of proanthocyanidins significantly (p<0.05) reduced the weight loss of fried chicken patties. Furthermore, a positive correlation was observed among pH, weight loss, and total HAA formation in all three groups (FP, BP, and Vc). Multivariate analysis showed that FP had a more pronounced effect than BP from the perspective of enhancing the quality of fried chicken patties and reducing the formation of HAAs. These results indicate that proanthocyanidins, both BP and FP, but especially FP, from Chinese quince can inhibit the formation of carcinogenic HAAs when added to protein-rich foods that are subsequently fried.

Risk Assessment of Polycyclic Aromatic Hydrocarbons and Heterocyclic Aromatic Amines in Processed Meat, Cooked Meat and Fish-Based Products Using the Margin of Exposure Approach.

The objective of this study is to assess the risk of exposure of polycyclic aromatic hydrocarbons (PAHs) and heterocyclic aromatic amines (HCAs) in meat and fish-based products marketed in Malaysia using the margin of exposure (MOE) approach. Benchmark Dose (BMD) software was used to model the BMD at a lower end of a one-sided 95% confidence interval with a 10% incremental risk (BMDL10) of PAHs and HCAs from different target organ toxicities. The MOEs of PAHs and HCAs in meat and fish-based products were determined by utilising the calculated BMDL10 values and estimated daily intake of meat and fish-based products from published data. The calculated BMDL10 values of PAHs (i.e. benzo[a]pyrene [BaP] and fluoranthene [FA]) and HCAs (i.e. 2-amino-3,8,dimethylimidazo[4,5-f]quinoxaline [MeIQx] and 2-amino-1-methyl-6-phenylimidazo[4,5,6]pyridine [PhIP]) ranged from 19 mg/kg bw/day to 71,801 mg/kg bw/day. The MOE of BaP ranged from 41,895 to 71,801 and that of FA ranged from 19 to 1412. As for MeIQx and PhIP, their MOEs ranged from 6,322 to 7,652 and from 2,362 to 14,390, respectively. The MOEs of FA, MeIQx and PhIP were lower than 10,000, indicating a high concern for human health and therefore demanding effective risk management actions.

Theoretical exploration of the phenolic compounds’ inhibition mechanism of heterocyclic aromatic amines in roasted beef patties by density functional theory

The ability of spices (bay leaf, star anise, and red pepper) and their characteristic phenolic compounds (quercetin, kaempferol, and capsaicin) to inhibit Heterocyclic aromatic amines (HAAs) in roasted beef patties were compared. Density functional theory (DFT) was used to reveal phenolic compounds interacting with HAAs-related intermediates and free radicals to explore possible inhibitory mechanisms for HAAs. 3 % red chili and 0.03 % capsaicin reduced the total HAAs content by 57.09 % and 68.79 %, respectively. DFT demonstrated that this was due to the stronger interaction between capsaicin and the β-carboline HAAs intermediate (Ebind = –32.95 kcal/mol). The interaction between quercetin and phenylacetaldehyde was found to be the strongest (Ebind = −17.47 kcal/mol). Additionally, DFT indicated that capsaicin reduced the carbonyl content by transferring hydrogen atoms (HAT) to eliminate HO·, HOO·, and carbon-centered alkyl radicals. This study provided a reference for the development of DFT in the control of HAAs.

In-situ growth of metal-organic frameworks on cellulose nanofiber aerogels for rapid adsorption of heterocyclic aromatic amines

Heterocyclic aromatic amines (HAAs) are the main carcinogens produced during thermal processing of protein-rich foods. In this paper, a composite aerogel (TOCNFCa) with a stabilized dual-network structure was prepared via a template for the in-situ synthesis of UiO-66 on cellulose for the adsorption of HAAs in food. The dual-network structure of TOCNFCa provides the composite aerogel with excellent wet strength, maintaining excellent compressive properties. With the in-situ grown UiO-66 content up to 71.89 wt%, the hierarchical porosity endowed TOCNFCa@UiO-66 with the ability to rapidly adsorb HAAs molecules with high capacity (1.44–5.82 μmol/g). Based on excellent thermal stability, adsorption capacity and anti-interference, TOCNFCa@UiO-66 achieved satisfactory recoveries of HAAs in the boiled marinade, which is faster and more economical than the conventional SPE method. Moreover, TOCNFCa@UiO-66 could maintain 84.55 % of the initial adsorption capacity after 5 times of reuse.

Effect of tea extracts on heterocyclic aromatic amines and advanced glycation end products in roasting Eleutheronema Tetradactylum and lipid-mediated inhibition mechanism analysis

Eleutheronema Tetradactylum is commercially important marine fish and a fixture at tables. However, nonnegligible hazardous substances, such as heterocyclic aromatic amines (HAAs) and advanced glycation end products (AGEs), generates along during thermal processing. Herein, we determined HAAs and two representative AGEs, Nε-carboxyethyl-lysine (CEL) and Nε-carboxymethyl-lysine (CML) formation in roasted Eleutheronema Tetradactylum, and proposed inhibitory method of tea polyphenol to effectively reduce HAAs, CML and CEL, which caused 51.23, 46.72, 24.06 and 35.48 percentage reduction of Norharman, Harman, CML and CEL, respectively, led IQ, 8-MeIQx below detected limitation. Precursors (amino acids, creatin(in)e, glucose and glyoxal), lipid oxidation, fatty acid analysis and further nontargeted lipidomic approaches are attempted to reveal the inhibition mechanism. This work develops a new method to minimize HAAs and AGEs in Eleutheronema Tetradactylum, provide a comprehensive interpretation of inhibition mechanism by tea polyphenols, which is helpful to food manufacturers for healthier fish production.

The Risk of Oral Cancer and the High Consumption of Thermally Processed Meat Containing Mutagenic and Carcinogenic Compounds.

The International Agency for Research on Cancer has classified the consumption of heat-processed meat as a direct human carcinogen and the consumption of red meat as a probable carcinogen. Mutagenic and carcinogenic compounds present in meat dishes include, among others, polycyclic aromatic hydrocarbons (PAHs) and heterocyclic aromatic amines (HAAs). These compounds can cause the development of gastrointestinal cancer. Oral cancer is one of the world's research priorities due to the ever-increasing incidence rate. However, the effect of diet on oral cancer is still a poorly recognized issue. The aim of this study was to assess the relationship between the risk of oral cancer and dietary ingredients with a particular emphasis on red meat and thermally processed meat. This study was conducted among patients with oral cancer in 2022 and 2023. The shortened standardized Food Frequency Questionnaire (FFQ) and a multivariate regression statistical analysis were used. The high consumption of red meat in general and thermally processed meat, especially smoked, fried, roasted and boiled, increases the risk of oral cavity cancer. Limiting the consumption of meat products and modifying the methods of preparing meat dishes may reduce exposure to carcinogenic compounds from the diet and thus reduce the risk of developing oral cancer.

Effects of Lipid on the Formation of Heterocyclic Aromatic Amines and Advanced Glycation End Products in Thermally Processed Fish

ABSTRACT The formation of hazardous substances, heterocyclic aromatic amines (HAAs) and two representative advanced glycation end products (AGEs), Nε-carboxymethyl-lysine (CML) and Nε-carboxyethyl-lysine (CEL) in five kinds of fish with different fat contents during thermal processing was investigated. The results indicated that HAAs, AGEs produced is related to the lipids in varying degrees. The variation of key precursors were examined to explain the relationship between fat oxidation and molecular pathway of HAAs and AGEs formation. The current research may help us better understand the overall generation of hazardous substances in food systems, and provide new ideas for formulating prevention in future production.