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Search Results (31)

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Keywords = n-nitrosamine compounds

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25 pages, 3256 KB  
Review
Developing Healthier Meat Products: Application of Natural Polyphenols to Reduce Hazardous Compounds During High Temperature Processing and Digestion
by Du-Xin Jin and Yu-Xuan Jin
Foods 2025, 14(22), 3952; https://doi.org/10.3390/foods14223952 - 18 Nov 2025
Viewed by 747
Abstract
Meat products are popularized worldwide for their great flavor and high nutritional value. However, a high consumption of high-temperature processed meat has posed an adverse health implication, contributing to an imperative demand for healthier meat products. Polyphenols are a category of compounds with [...] Read more.
Meat products are popularized worldwide for their great flavor and high nutritional value. However, a high consumption of high-temperature processed meat has posed an adverse health implication, contributing to an imperative demand for healthier meat products. Polyphenols are a category of compounds with excellent antioxidant and antimicrobial properties. Accumulating evidence has demonstrated that polyphenols can reduce carcinogen formation, particularly heterocyclic aromatic amines (HAAs), polycyclic aromatic hydrocarbons (PAHs), and N-nitrosamines (NAs), during thermal processing of meat. Notably, polyphenols can mitigate lipid and protein oxidation during the gastrointestinal digestion of meat, underscoring the role of antioxidant polyphenols in enhancing meat consumption safety. To promote the application of polyphenols in mitigating hazardous compounds in meat products, this review elucidates polyphenols’ mitigation mechanisms against thermally generated carcinogens in meat products, analyzing their multilevel suppression pathways during processing and subsequent digestive transformation through gastrointestinal interfaces. Furthermore, this article proposes an encapsulation strategy for polyphenols to address their inherent low aqueous solubility and detrimental effects on sensory properties in meat products, aiming to enhance bioavailability while minimizing adverse organoleptic impacts. This review can provide new strategies for the application of polyphenols in developing healthier meat products and to indicate a feasible direction for future research. Full article
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14 pages, 1028 KB  
Article
Tobacco Smoke Exposure Biomarker Profiles and Healthcare Utilization Patterns Among U.S. Children
by Ashley L. Merianos, Georg E. Matt, Roman A. Jandarov and E. Melinda Mahabee-Gittens
Toxics 2025, 13(11), 909; https://doi.org/10.3390/toxics13110909 - 23 Oct 2025
Viewed by 726
Abstract
This study aimed to examine the associations between distinct tobacco smoke exposure (TSE) biomarkers and healthcare utilization patterns in U.S. children ages 3–11 years with and without current asthma. Secondary data from the 2013–2016 National Health and Nutrition Examination Survey were analyzed (N [...] Read more.
This study aimed to examine the associations between distinct tobacco smoke exposure (TSE) biomarkers and healthcare utilization patterns in U.S. children ages 3–11 years with and without current asthma. Secondary data from the 2013–2016 National Health and Nutrition Examination Survey were analyzed (N = 2838). TSE biomarkers included serum cotinine, urinary total nicotine equivalents (TNE2), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), the NNAL/TNE2 ratio, and the N-acetyl-S-(2-cyanoethyl)-L-cysteine (2CyEMA)/TNE2 ratio. We conducted Poisson regression analyses to examine the associations between each biomarker and healthcare visits and hospitalizations within the past 12 months, adjusting for sociodemographic and home TSE covariates. Children without asthma who had higher urinary TNE2 levels (adjusted incidence rate ratio [aIRR] = 1.03, 95% confidence interval [CI] = 1.02–1.04) and children with asthma who had higher urinary 2CyEMA/TNE2 ratio levels (aIRR = 1.05, 95%CI = 1.03–1.07) were at an increased risk of having more healthcare visits. Children without asthma who had higher serum cotinine (aIRR = 1.21, 95%CI = 1.07–1.37) and higher 2CyEMA/TNE2 ratio levels (aIRR = 1.25, 95%CI = 1.14–1.37) were at an increased risk of hospitalizations. Children with asthma who had higher NNAL/TNE2 ratio levels (aIRR = 1.52, 95%CI = 1.11–2.09) were at increased risk of hospitalizations. It is important to consider comprehensive biomarkers of TSE in children, such as TNE, tobacco-specific nitrosamines, and volatile organic compounds, along with healthcare utilization patterns. Child TSE reduction policies are urgently needed. Full article
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20 pages, 1188 KB  
Article
Assessing Nitrosamine Migration from Drinking Water Contact Materials Using a Validated LLE-GC-MS Method
by Beatriz Antunes, Andreia Videira, Ana Penetra, Vitor V. Cardoso, Rui N. Carneiro and Cristina M. M. Almeida
Molecules 2025, 30(11), 2403; https://doi.org/10.3390/molecules30112403 - 30 May 2025
Cited by 1 | Viewed by 1663
Abstract
Nitrosamines (NAs) are toxic compounds associated with disinfection processes. Human exposure can occur through the hydraulic hoses and seals that are in contact with drinking water. This study develops and validates a chromatographic method to quantify 11 NAs in water leachates from four [...] Read more.
Nitrosamines (NAs) are toxic compounds associated with disinfection processes. Human exposure can occur through the hydraulic hoses and seals that are in contact with drinking water. This study develops and validates a chromatographic method to quantify 11 NAs in water leachates from four organic materials. The method is based on liquid–liquid extraction (LLE) followed by gas chromatography coupled with mass spectrometry (GC-MS). The method was validated by the application of several statistical tests, namely, linearity/working range, precision, trueness, and recovery tests. The GC-MS method showed a good linear range for all NAs with coefficients of determination (r2) higher than 0.9989, coefficients of variation of the method (CVm) lower than 2.5%, and PG < F (0.05; 1; N-3). The working range varies between 10 µg/L and 386.7 µg/L. The GC-MS method showed good precision under repeatability and reproducibility conditions with a relative standard deviation (RSD) lower than 12% and 10%, respectively. The GC-MS showed good trueness with a relative error lower than 20%. Matrix effects were significant, with recovery (Rec) values between 47% and 125% and an RSD lower than 20%. The limit of detection (LOD) and quantification (LOQ) ranged between 0.71 µg/L and 8.9 µg/L and between 2.3 µg/L and 29.8 µg/L, respectively. The method quantification limits (MQL) ranged from 0.0045 µg/L to 0.0378 µg/L. The sum of the MQL (0.2 µg/L) is lower than the reference limit of 0.3 µg/L for NAs in the leachates from the migration tests. Four organic materials were subjected to migration tests with demineralized and chlorinated water to assess their suitability for the water supply system. These materials met the NA specifications for use in the water network. Full article
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24 pages, 1625 KB  
Review
Nitric Oxide in Parkinson’s Disease: The Potential Role of Dietary Nitrate in Enhancing Cognitive and Motor Health via the Nitrate–Nitrite–Nitric Oxide Pathway
by Gianluca Tripodi, Mauro Lombardo, Sercan Kerav, Gilda Aiello and Sara Baldelli
Nutrients 2025, 17(3), 393; https://doi.org/10.3390/nu17030393 - 22 Jan 2025
Cited by 13 | Viewed by 6349
Abstract
Background/Objectives: Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, leading to motor symptoms such as tremor, rigidity, and bradykinesia. The pathological hallmarks of PD include Lewy bodies and mechanisms [...] Read more.
Background/Objectives: Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, leading to motor symptoms such as tremor, rigidity, and bradykinesia. The pathological hallmarks of PD include Lewy bodies and mechanisms like oxidative/nitrosative stress, chronic inflammation, and mitochondrial dysfunction. Nitric oxide (NO), produced by nitric oxide synthase (NOS) isoforms, plays a dual role in neuroprotection and neurodegeneration. Excessive NO production exacerbates neuroinflammation and oxidative/nitrosative damage, contributing to dopaminergic cell death. This review explores NO’s role in PD pathogenesis and investigates dietary nitrate as a therapeutic strategy to regulate NO levels. Methods: A literature review of studies addressing the role of NO in PD was conducted using major scientific databases, including PubMed, Scopus, and Web of Science, using keywords such as “nitric oxide”, “NOSs”, “Parkinson’s disease”, and “nitrate neuroprotection in PD”. Studies on nitrate metabolism via the nitrate–nitrite–NO pathway and its effects on PD hallmarks were analyzed. Studies regarding the role of nitrosamine formation in PD, which are mainly formed during the nitrification process of amines (nitrogen-containing compounds), often due to chemical reactions in the presence of nitrite or nitrate, were also examined. In particular, nitrate has been shown to induce oxidative stress, affect the mitochondrial function, and contribute to inflammatory phenomena in the brain, another factor closely related to the pathogenesis of PD. Results: Excessive NO production, particularly from iNOS and nNOS, was strongly associated with neuroinflammation and oxidative/nitrosative stress, amplifying neuronal damage in PD. Dietary nitrate was shown to enhance NO bioavailability through the nitrate–nitrite–NO pathway, mitigating inflammation and oxidative/nitrosative damage. Conclusions: Dysregulated NO production contributes significantly to PD progression via inflammatory and oxidative/nitrosative pathways. Dietary nitrate, by modulating NO levels, offers a promising therapeutic strategy to counteract these pathological mechanisms. Further clinical trials are warranted to establish its efficacy and optimize its use in PD management. Full article
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20 pages, 1205 KB  
Article
Residual Nitrite, Nitrate, and Volatile N-Nitrosamines in Organic and Conventional Ham and Salami Products
by Kathrine H. Bak, Susanne Bauer, Christoph Eisenreich and Peter Paulsen
Foods 2025, 14(1), 112; https://doi.org/10.3390/foods14010112 - 3 Jan 2025
Cited by 7 | Viewed by 6190
Abstract
Nitrite and nitrate in meat products may be perceived negatively by consumers. These compounds can react to form carcinogenic volatile N-nitrosamines. “Nitrite-free” (i.e., uncured) organic meat products may contain nitrate from natural sources (e.g., spices and water). We studied the quality of ham [...] Read more.
Nitrite and nitrate in meat products may be perceived negatively by consumers. These compounds can react to form carcinogenic volatile N-nitrosamines. “Nitrite-free” (i.e., uncured) organic meat products may contain nitrate from natural sources (e.g., spices and water). We studied the quality of ham and salami (conventional cured; organic cured; organic uncured). Residual nitrite and nitrate, volatile N-nitrosamines, microbial load, surface color, water activity, and pH were determined, considering one week of refrigerated storage in open or unopened packages. Residual nitrite and nitrate in organic, uncured salami were similar to cured salami, presumably from the addition of herbs and spices and nitrate reduction by nitrate reductase from microorganisms. For cooked ham, residual nitrite was significantly lower in the organic, uncured sample, while residual nitrate was not detected. N-nitrosodiphenylamine was detected in all samples at day 0, exceeding, in three out of five cured and both uncured products, the US legal limit of 10 µg/kg of volatile N-nitrosamines in foods. This finding warrants further investigation. The microbial load in salami products was dominated by bacteria from starter cultures. In ham, a slight increase in total aerobic count and lactic acid bacteria during storage was noted. Overall, the microbial quality of the products was as expected for the respective product types. Full article
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14 pages, 1066 KB  
Article
Using Celery Powder in a Semi-Dry Fermented Sausage ‘Heat-Treated Sucuk’: Nitrosamine Formation, Lipid Oxidation, and Volatile Compounds
by Zeynep Feyza Yılmaz Oral, Mükerrem Kaya and Güzin Kaban
Foods 2024, 13(20), 3306; https://doi.org/10.3390/foods13203306 - 18 Oct 2024
Cited by 3 | Viewed by 2798
Abstract
This study investigated the effect of using celery powder (CP) as source of pre-converted nitrite (treatments: A: 150 mg/kg NaNO2, B: 100 mg/kg NaNO2 + CP as 50 mg/kg NaNO2 equivalent, C: 50 mg/kg NaNO2 + CP as [...] Read more.
This study investigated the effect of using celery powder (CP) as source of pre-converted nitrite (treatments: A: 150 mg/kg NaNO2, B: 100 mg/kg NaNO2 + CP as 50 mg/kg NaNO2 equivalent, C: 50 mg/kg NaNO2 + CP as 100 mg/kg NaNO2 equivalent, D: CP as 150 mg/kg NaNO2 equivalent) on the physicochemical and microbiological properties in heat-treated sucuk (HTS), a kind of semi-dry fermented sausage. The influence of cooking time (CT) on the nitrosamine formation in HTS with and without CP was also determined. The results indicated that the use of CP increased the pH value and decreased the aw value. Micrococcus/Staphylococcus and residual nitrite were not affected by the use of CP. TBARS value varied from 0.78 to 0.90 mg MDA/kg. CP did not affect the abundance of hexanal in HTS, however, it increased the abundance of camphene. The results of PCA showed that treatments A, B, and C had similar volatile compound profiles. CP did not affect both N-nitrosodimethylamine and N-nitrosodiethylamine, but their levels increased as the CT increased. Increased CT also resulted in increased N-nitrosopiperidine (NPIP) in all treatments, but the cooking for 1 min did not cause a significant increase in treatments A, B, and C. CP leads to a significant increase in NPIP content, especially after 3 and 5 min of cooking in HTS. Full article
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24 pages, 30669 KB  
Article
Maximizing N-Nitrosamine Rejection via RO Membrane Plugging with Hexylamine and Hexamethylenediamine
by Silvia Morović, Katarina Marija Drmić, Sandra Babić and Krešimir Košutić
Nanomaterials 2024, 14(13), 1117; https://doi.org/10.3390/nano14131117 - 28 Jun 2024
Cited by 5 | Viewed by 2145
Abstract
The rapid expansion of urban areas and the increasing demand for water resources necessitate substantial investments in technologies that enable the reuse of municipal wastewater for various purposes. Nonetheless, numerous challenges remain, particularly regarding disinfection by-products (DBPs), especially carcinogenic compounds such as N [...] Read more.
The rapid expansion of urban areas and the increasing demand for water resources necessitate substantial investments in technologies that enable the reuse of municipal wastewater for various purposes. Nonetheless, numerous challenges remain, particularly regarding disinfection by-products (DBPs), especially carcinogenic compounds such as N-nitrosamines (NTRs). To tackle the ongoing issues associated with reverse osmosis (RO) membranes, this study investigated the rejection of NTRs across a range of commercially available RO membranes. In addition, the research aimed to improve rejection rates by integrating molecular plugs into the nanopores of the polyamide (PA) layer. Hexylamine (HEX) and hexamethylenediamine (HDMA), both linear chain amines, have proven to be effective as molecular plugs for enhancing the removal of NTRs. Given the environmental and human health concerns associated with linear amines, the study also aimed to assess the feasibility of diamine molecules as potential alternatives. The application of molecular plugs led to changes in pore size distribution (PSD) and effective pore number, resulting in a decrease in membrane permeability (from 5 to 33%), while maintaining levels suitable for RO processes. HEX and HDMA exhibited a positive effect on NTR rejection with ACM1, ACM5 and BW30LE membranes. In particular, NDMA rejection, the smallest molecule of the tested NTRs, with ACM1 was improved by 65.5% and 70.6% after treatment with HEX and HDMA, respectively. Full article
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30 pages, 1707 KB  
Review
Plant-Based Meat Analogues in the Human Diet: What Are the Hazards?
by Maria Gräfenhahn and Michael Beyrer
Foods 2024, 13(10), 1541; https://doi.org/10.3390/foods13101541 - 15 May 2024
Cited by 17 | Viewed by 7962
Abstract
Research regarding meat analogues is mostly based on formulation and process development. Information concerning their safety, shelf life, and long-term nutritional and health effects is limited. This article reviews the existing literature and analyzes potential hazards introduced or modified throughout the processing chain [...] Read more.
Research regarding meat analogues is mostly based on formulation and process development. Information concerning their safety, shelf life, and long-term nutritional and health effects is limited. This article reviews the existing literature and analyzes potential hazards introduced or modified throughout the processing chain of plant-based meat analogues via extrusion processing, encompassing nutritional, microbiological, chemical, and allergen aspects. It was found that the nutritional value of plant-based raw materials and proteins extracted thereof increases along the processing chain. However, the nutritional value of plant-based meat analogues is lower than that of e.g., animal-based products. Consequently, higher quantities of these products might be needed to achieve a nutritional profile similar to e.g., meat. This could lead to an increased ingestion of undigestible proteins and dietary fiber. Although dietary fibers are known to have many positive health benefits, they present a hazard since their consumption at high concentrations might lead to gastrointestinal reactions. Even though there is plenty of ongoing research on this topic, it is still not clear how the sole absorption of metabolites derived from plant-based products compared with animal-based products ultimately affects human health. Allergens were identified as a hazard since plant-based proteins can induce an allergic reaction, are known to have cross-reactivities with other allergens and cannot be eliminated during the processing of meat analogues. Microbiological hazards, especially the occurrence of spore- and non-spore-forming bacteria, do not represent a particular case if requirements and regulations are met. Lastly, it was concluded that there are still many unknown variables and open questions regarding potential hazards possibly present in meat analogues, including processing-related compounds such as n-nitrosamines, acrylamide, and heterocyclic aromatic amino acids. Full article
(This article belongs to the Section Food Nutrition)
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18 pages, 1191 KB  
Review
Red Meat Heating Processes, Toxic Compounds Production and Nutritional Parameters Changes: What about Risk–Benefit?
by Marco Iammarino, Rosaria Marino, Valeria Nardelli, Mariateresa Ingegno and Marzia Albenzio
Foods 2024, 13(3), 445; https://doi.org/10.3390/foods13030445 - 30 Jan 2024
Cited by 17 | Viewed by 8916
Abstract
The heating process is a crucial step that can lead to the formation of several harmful chemical compounds in red meat such as heterocyclic aromatic amines, N-Nitrosamines, polycyclic aromatic hydrocarbons and acrylamide. Meat has high nutritional value, providing essential amino acids, bioactive compounds [...] Read more.
The heating process is a crucial step that can lead to the formation of several harmful chemical compounds in red meat such as heterocyclic aromatic amines, N-Nitrosamines, polycyclic aromatic hydrocarbons and acrylamide. Meat has high nutritional value, providing essential amino acids, bioactive compounds and several important micronutrients which can also be affected by heating processes. This review aims to provide an updated overview of the effects of different heating processes on both the safety and nutritional parameters of cooked red meat. The most-used heating processes practices were taken into consideration in order to develop a risk–benefit scenario for each type of heating process and red meat. Full article
(This article belongs to the Special Issue Strategies to Improve the Functional Value of Meat and Meat Products)
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10 pages, 1280 KB  
Article
N-Nitrosamine Impurities in Ethalfluralin: Determination of an Overlooked Deleterious Source in Pesticides
by George P. Balayiannis and Helen Karasali
Agriculture 2023, 13(5), 1104; https://doi.org/10.3390/agriculture13051104 - 22 May 2023
Cited by 3 | Viewed by 2892
Abstract
N-nitrosamines are a class of carcinogenic chemical compound. Considering the large-scale application of agrochemicals globally, the elimination of N-nitrosamines from pesticides should be a priority for manufacturers and regulators. A set of methods was developed and validated for the determination of [...] Read more.
N-nitrosamines are a class of carcinogenic chemical compound. Considering the large-scale application of agrochemicals globally, the elimination of N-nitrosamines from pesticides should be a priority for manufacturers and regulators. A set of methods was developed and validated for the determination of the toxicologically relevant N-nitrosamine impurity of ethalfluralin (ethyl-N-(2-methylallyl) N-nitroso amine—EMANA) in 33% w v−1 emulsifiable concentrate (EC) formulations. Solid Phase Extraction (SPE) was compared with the “dilute and shoot” approach. Gas chromatography (GC) was combined with Flame Ionization Detection (FID) and mass spectrometry (MS). For MS, two mass filtering modes (Selective Ion Monitoring—SIM, tandem mass spectrometry—MS/MS) and two ionization modes (Electron Ionization—EI, Positive chemical ionization—PCI) were applied. It was concluded that, in the case of samples with high nitrosamine concentration (>90 μg g−1), the “dilute and shoot” approach can be applied without compromising the quality of the results. SPE, however, is required to attain the LOQ (0.33 μg g−1) with good recovery (97.4–110.67%), linearity (R > 0.99) and precision (%RSD 0.68–1.74). The LOQ supersedes the limit set by EFSA (1 μg g−1) in the Technical Active Substance—TAS. The concentration range of the methods is 0.05–110 μg g−1. The methods were applied for the official surveillance program of the Greek agrochemicals market. Full article
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34 pages, 4663 KB  
Review
DNA Alkylation Damage by Nitrosamines and Relevant DNA Repair Pathways
by Jörg Fahrer and Markus Christmann
Int. J. Mol. Sci. 2023, 24(5), 4684; https://doi.org/10.3390/ijms24054684 - 28 Feb 2023
Cited by 62 | Viewed by 12971
Abstract
Nitrosamines occur widespread in food, drinking water, cosmetics, as well as tobacco smoke and can arise endogenously. More recently, nitrosamines have been detected as impurities in various drugs. This is of particular concern as nitrosamines are alkylating agents that are genotoxic and carcinogenic. [...] Read more.
Nitrosamines occur widespread in food, drinking water, cosmetics, as well as tobacco smoke and can arise endogenously. More recently, nitrosamines have been detected as impurities in various drugs. This is of particular concern as nitrosamines are alkylating agents that are genotoxic and carcinogenic. We first summarize the current knowledge on the different sources and chemical nature of alkylating agents with a focus on relevant nitrosamines. Subsequently, we present the major DNA alkylation adducts induced by nitrosamines upon their metabolic activation by CYP450 monooxygenases. We then describe the DNA repair pathways engaged by the various DNA alkylation adducts, which include base excision repair, direct damage reversal by MGMT and ALKBH, as well as nucleotide excision repair. Their roles in the protection against the genotoxic and carcinogenic effects of nitrosamines are highlighted. Finally, we address DNA translesion synthesis as a DNA damage tolerance mechanism relevant to DNA alkylation adducts. Full article
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18 pages, 1066 KB  
Article
Reduction of Nitrite in Canned Pork through the Application of Black Currant (Ribes nigrum L.) Leaves Extract
by Karolina M. Wójciak, Karolina Ferysiuk, Paulina Kęska, Małgorzata Materska, Barbara Chilczuk, Monika Trząskowska, Marcin Kruk, Danuta Kołożyn-Krajewska and Rubén Domínguez
Molecules 2023, 28(4), 1749; https://doi.org/10.3390/molecules28041749 - 12 Feb 2023
Cited by 11 | Viewed by 2831
Abstract
Sodium nitrite is a multifunctional additive commonly used in the meat industry. However, this compound has carcinogenic potential, and its use should be limited. Therefore, in this study the possibility of reducing the amount of sodium(III) nitrite added to canned meat from 100 [...] Read more.
Sodium nitrite is a multifunctional additive commonly used in the meat industry. However, this compound has carcinogenic potential, and its use should be limited. Therefore, in this study the possibility of reducing the amount of sodium(III) nitrite added to canned meat from 100 to 50 mg/kg, while enriching it with freeze-dried blackcurrant leaf extract, was analyzed. The possibility of fortification of canned meat with blackcurrant leaf extract was confirmed. It contained significant amounts of phenolic acids and flavonoid derivatives. These compounds contributed to their antioxidant activity and their ability to inhibit the growth of selected Gram-positive bacteria. In addition, it was observed that among the three different tested doses (50, 100, and 150 mg/kg) of the blackcurrant leaf extract, the addition of the highest dose allowed the preservation of the antioxidant properties of canned meat during 180 days of storage (4 °C). At the end of the storage period, this variant was characterized by antiradical activity against ABTS (at the level of 4.04 mgTrolox/mL) and the highest reducing capacity. The addition of 150 mg/kg of blackcurrant leaf extract caused a reduction in oxidative transformations of fat in meat products during the entire storage period, reaching a level of TBARS almost two times less than in the control sample. In addition, these products were generally characterized by stability (or slight fluctuations) of color parameters and good microbiological quality and did not contain N-nitrosamines. Full article
(This article belongs to the Special Issue Bioactive Compounds from Functional Foods)
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25 pages, 2706 KB  
Article
The Degradation Product of Ramipril Is Potentially Carcinogenic, Genotoxic and Mutagenic
by Katarzyna Regulska, Agnieszka Matera-Witkiewicz, Aleksandra Mikołajczyk and Beata J. Stanisz
Appl. Sci. 2023, 13(4), 2358; https://doi.org/10.3390/app13042358 - 12 Feb 2023
Cited by 8 | Viewed by 4544
Abstract
(1) Background: The aim of this study was to identify the degradation product of ramipril (RAM) formed under dry air and to verify its potential modes of carcinogenicity. We intended to check whether its formation and presence in final dosage forms could pose [...] Read more.
(1) Background: The aim of this study was to identify the degradation product of ramipril (RAM) formed under dry air and to verify its potential modes of carcinogenicity. We intended to check whether its formation and presence in final dosage forms could pose a cancer risk to humans who are treated with RAM due to cardiological indications. The carcinogenicity of this compound was evaluated with respect to two mechanisms: a potential direct DNA-damage and indirect toxicity, secondary to forming mutagenic N-nitroso metabolites. (2) Methods: Firstly, a forced ageing test under dry air was conducted for pure RAM in order to induce its degradation. The validated HPLC system was used to describe the kinetic order of this reaction. The emerging degradation impurity was identified by HPLC-MS. In the second stage, the cancer risk of the identified RAM degradant was predicted using a structure-based assessment by in silico QSAR model, employing three endpoints: carcinogenicity, genotoxicity and mutagenicity. In the third stage, the obtained QSAR results were experimentally verified. To verify genotoxicity prediction, in vitro micronucleus assay was employed. It enabled us to assess the potential direct DNA-damaging properties of RAM degradant at high concentrations (as screening series) and at concentrations usually observed in human blood (to mimic the clinical scenario). To verify the QSAR mutagenicity prediction, an in vitro Ames test was carried out. It was designed so as to detect two mechanisms of mutagenicity: a direct one (for pure degradant) and an indirect one (via N-nitroso-metabolites formation). N-nitroso-metabolites for mutagenicity assessment were obtained using NAP test. (3) Results: The kinetic mechanism of RAM degradation was first-order, the degradation rate constant was k = 1.396 ± 0.133 × 10−5 s−1 (T = 373 K), thus the formation of impurity was rapid. Energy of activation was 174.12 ± 46.2 kJ/mol, entropy was positive, thus reaction was bimolecular and favored; enthalpy was 171.65 ± 48.7 kJ/mol, thus reaction was endothermic. Only one degradation impurity was formed, and it was identified as RAM diketopiperazine derivative (DKP). QSAR simulation predicted that DKP could be carcinogenic and genotoxic, but this result had only moderate reliability. DKP was also predicted to be non-mutagenic and this prediction was strong (endpoint score 0.2). The confirmatory micronucleus experiment for genotoxicity prediction suggested that DKP was cytotoxic and it could be also aneugenic at a high concentration (0.22 mg/mL), evidenced by a three-fold increase in micronuclei relative to the control (11.86:33.33%, p = 0.0184). At physiologic concentrations, its cytotoxicity and genotoxicity did not occur. This means that the genotoxicity of DKP was limited by a threshold mechanism. In the mutagenicity in vitro assessment, pure DKP was not mutagenic, but its nitrosation product induced base substitutions mutations in test bacteria TA100 following metabolic activation at a concentration of 4.5 mg/mL, confirming its mutagenicity. (4) Conclusions: RAM rapidly cyclizes to diketopiperazine derivative under dry air. This impurity resides in drugs administered to patients. DKP is potentially aneugenic and cytotoxic at high concentrations, yet at concentrations typically occurring in human blood, this effect is unlikely. The exposure of patients to high concentrations of DKP, exceeding the typical blood level and standard RAM dosing, could lead to cancer development, thus the safe threshold for human exposure to DKP must be verified in follow-up in vivo experiments. Based on our results, it is impossible to establish the maximum safe dose of pure DKP to humans. Furthermore, DKP itself is not mutagenic, but it is liable to the formation of mutagenic nitroso-metabolites in vivo. Nitroso-derivatives of DKP are in vitro mutagens and their real-life impact on humans must be further evaluated in in vivo studies. Until this is carried out, RAM should not be formulated by manufacturers using dry procedures to minimize DKP formation and reduce risk of human carcinogenesis, since DKP could cause cancer via two independent mechanisms: direct genotoxicity when the exposure over standard RAM dosing occurs, and indirect mutagenicity via in vivo N-nitrosamine formation. Full article
(This article belongs to the Special Issue Toxicity of Chemicals: Evaluation, Analysis and Impact)
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14 pages, 1824 KB  
Article
Investigation on the Contents of Nε-carboxymethyllysine, Nε-carboxyethyllysine, and N-nitrosamines in Commercial Sausages on the Chinese Market
by Wenjing Wang, Yafei Kou, Yanli Du, Mingyu Li, Jian Zhang, Aiping Yan, Jianhua Xie and Mingyue Shen
Foods 2023, 12(4), 724; https://doi.org/10.3390/foods12040724 - 7 Feb 2023
Cited by 9 | Viewed by 2775
Abstract
Sausages are among the most popular meat products worldwide. However, some harmful products, such as advanced glycation end-products (AGEs) and N-nitrosamines (NAs), can be formed simultaneously during sausage processing. In this study, the contents of AGEs, NAs, α-dicarbonyls and the proximate composition were [...] Read more.
Sausages are among the most popular meat products worldwide. However, some harmful products, such as advanced glycation end-products (AGEs) and N-nitrosamines (NAs), can be formed simultaneously during sausage processing. In this study, the contents of AGEs, NAs, α-dicarbonyls and the proximate composition were investigated in two kinds of commercial sausages (fermented sausages and cooked sausages) in the Chinese market. The correlations among them were further analyzed. The results showed that the fermented and cooked sausages had different in protein/fat contents and pH/thiobarbituric acid reactive substance values due to their different processing technologies and added ingredients. The Nε-carboxymethyllysine (CML) and Nε-carboxyethyllysine (CEL) concentrations varied from 3.67 to 46.11 mg/kg and from 5.89 to 52.32 mg/kg, respectively, and the NAs concentrations ranged from 1.35 to 15.88 µg/kg. The contents of some hazardous compounds, such as CML, N-nitrosodimethylamine, and N-nitrosopiperidine, were observed to be higher in the fermented sausages than in the cooked sausages. Moreover, levels of NAs in some sausage samples exceeded the limit of 10 µg/kg issued by the United States Department of Agriculture, suggesting that particular attention should be paid to mitigating NAs, especially in fermented sausages. The correlation analysis suggested that the levels of AGEs and NAs were not significantly correlated in both kinds of sausages. Full article
(This article belongs to the Special Issue Chemical Contaminants and Food Quality)
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19 pages, 356 KB  
Review
A Review on the Role of Lactic Acid Bacteria in the Formation and Reduction of Volatile Nitrosamines in Fermented Sausages
by Selen Sallan, Zeynep Feyza Yılmaz Oral and Mükerrem Kaya
Foods 2023, 12(4), 702; https://doi.org/10.3390/foods12040702 - 6 Feb 2023
Cited by 26 | Viewed by 5718
Abstract
Nitrosamines are N-nitroso compounds with carcinogenic, mutagenic and teratogenic properties. These compounds could be found at certain levels in fermented sausages. Fermented sausages are considered to be a suitable environment for nitrosamine formation due to acid formation and reactions such as proteolysis [...] Read more.
Nitrosamines are N-nitroso compounds with carcinogenic, mutagenic and teratogenic properties. These compounds could be found at certain levels in fermented sausages. Fermented sausages are considered to be a suitable environment for nitrosamine formation due to acid formation and reactions such as proteolysis and lipolysis during ripening. However, lactic acid bacteria (spontaneous or starter culture), which constitute the dominant microbiota, contribute significantly to nitrosamine reduction by reducing the amount of residual nitrite through nitrite degradation, and pH decrease has an important effect on the residual nitrite amount as well. These bacteria also play an indirect role in nitrosamine reduction by suppressing the growth of bacteria that form precursors such as biogenic amines. In recent years, research interest has focused on the degradation or metabolization of nitrosamines by lactic acid bacteria. The mechanism by which these effects are seen has not been fully understood yet. In this study, the roles of lactic acid bacteria on nitrosamine formation and their indirect or direct effects on reduction of volatile nitrosamines are discussed. Full article
(This article belongs to the Special Issue Safety of Processed Meat Products)
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