scholarly journals In Vitro Genotoxicity Assessment of Functional Ingredients: Betaine, Choline, and Taurine

Foods ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 339
Author(s):  
Julen Sanz-Serrano ◽  
Ariane Vettorazzi ◽  
Damian Muruzabal ◽  
Amaya Azqueta ◽  
Adela López de Cerain

This article focuses on a complete in vitro genotoxicity assessment of three nutrients widely used as functional ingredients in the European market: betaine, choline, and taurine. The European Food Safety Authority (EFSA) tiered approach for food additives in concordance with the safety assessment of chemicals in food developed by Food and Agriculture Organization/World Health Organization (FAO/WHO) was followed; the miniaturized Ames test in Salmonella typhimurium TA97a, TA98, TA100, TA102, and TA1535 strains (following the principles of Organization for Economic Co-operation and Development (OECD) 471), and the micronucleus test (OECD 487) in TK6 cells were performed. In addition, the in vitro standard and enzyme-modified (human 8-oxoguanine DNA glycosylase 1 (hOGG), endonuclease III (EndoIII), 3-alkyladenine DNA glycosylase (hAAG)) comet assay (S9−/S9+) was conducted in order to assess the potential premutagenic lesions in TK6 cells. None of the compounds produced any signs of genotoxicity in any of the conditions tested. This article increases the limited evidence available and complements the EFSA recommendations for the in vitro genotoxicity testing of nutrients.

2002 ◽  
Vol 49 (1) ◽  
pp. 145-155 ◽  
Author(s):  
Janusz Błasiak ◽  
Ewa Gloc ◽  
Mariusz Warszawski

Idarubicin is an anthracycline antibiotic used in cancer therapy. Mitoxantrone is an anthracycline analog with presumed better antineoplastic activity and lesser toxicity. Using the alkaline comet assaywe showed that the drugs at 0.01-10 microM induced DNA damage in normal human lymphocytes. The effect induced by idarubicin was more pronounced than by mitoxantrone (P < 0.001). The cells treated with mitoxantrone at 1 microM were able to repair damage to their DNA within a 30-min incubation, whereas the lymphocytes exposed to idarubicin needed 180 min. Since anthracyclines are known to produce free radicals, we checked whether reactive oxygen species might be involved in the observed DNA damage. Catalase, an enzyme inactivating hydrogen peroxide, decreased the extent of DNA damage induced by idarubicin, but did not affect the extent evoked by mitoxantrone. Lymphocytes exposed to the drugs and treated with endonuclease III or formamidopyrimidine-DNA glycosylase (Fpg), enzymes recognizing and nicking oxidized bases, displayed a higher level of DNA damage than the untreated ones. 3-Methyladenine-DNA glycosylase II (AlkA), an enzyme recognizing and nicking mainly methylated bases in DNA, increased the extent of DNA damage caused by idarubicin, but not that induced by mitoxantrone. Our results indicate that the induction of secondary malignancies should be taken into account as side effects of the two drugs. Direct strand breaks, oxidation and methylation of the DNA bases can underlie the DNA-damaging effect of idarubicin, whereas mitoxantrone can induce strand breaks and modification of the bases, including oxidation. The observed in normal lymphocytes much lesser genotoxicity of mitoxantrone compared to idarubicin should be taken into account in planning chemotherapeutic strategies.


2020 ◽  
Vol 11 (SPL1) ◽  
pp. 1278-1285
Author(s):  
Mohamed Yafout ◽  
Amine Ousaid ◽  
Ibrahim Sbai El Otmani ◽  
Youssef Khayati ◽  
Amal Ait Haj Said

The new SARS-CoV-2 belonging to the coronaviruses family has caused a pandemic affecting millions of people around the world. This pandemic has been declared by the World Health Organization as an international public health emergency. Although several clinical trials involving a large number of drugs are currently underway, no treatment protocol for COVID-19 has been officially approved so far. Here we demonstrate through a search in the scientific literature that the traditional Moroccan pharmacopoeia, which includes more than 500 medicinal plants, is a fascinating and promising source for the research of natural molecules active against SARS-CoV-2. Multiple in-silico and in-vitro studies showed that some of the medicinal plants used by Moroccans for centuries possess inhibitory activity against SARS-CoV or SARS-CoV-2. These inhibitory activities are achieved through the different molecular mechanisms of virus penetration and replication, or indirectly through stimulation of immunity. Thus, the potential of plants, plant extracts and molecules derived from plants that are traditionally used in Morocco and have activity against SARS-CoV-2, could be explored in the search for a preventive or curative treatment against COVID-19. Furthermore, safe plants or plant extracts that are proven to stimulate immunity could be officially recommended by governments as nutritional supplements.


2018 ◽  
Vol 28 (4) ◽  
pp. 1213-1217
Author(s):  
Jovana Džoljić ◽  
Ljiljana Đorđević

Food and Agricultural Organization as a “sweeteners” consider products used for sweetening derived from sugar crops, cereals, fruits or milk, or that are produced by insects. Sweeteners, as an additive, have important role for technological functions of food, especially in providing texture, bulk and color, and also as preservative agents. Regardless the numerous sweeteners, alternative sweeteners to sucrose are in main focus for implementation in food industry. Nowadays Food and Agricultural Organization and World Health Organization Food standards, Codex Alimentarius Commission (2018) accepted list of 27 food additives that have the functional class “sweetener”. Nowadays, alternative sweeteners and their application in food technology are in main focus of scientist. Stevia plant stands for one of the most important natural intense sweetener, since stevia glycosides are almost 400 times sweeter than sucrose. Extracts of stevia represents a powerful tool for reducing sugars in food and beverages, which can be acceptable substitutes to full sugar versions of this products. Regarding the data of Euromonitor international, new food products containing stevia grew 10% from 2016 to 2017. The biggest increment in stevia use was noticed in categories of snacks, juice drinks, dairy, carbonated soft drinks and confectionery. Barriocanal et al. (2008) highlighted that safety studies reported no negative side effects of stevia use. Can be expected that in recent future use of S. rebaudiana as sweetener would be extended to almost all the world’s countries, regarding all discovered beneficial health effects.


Author(s):  
Lara Bittmann

On December 31, 2019, WHO was informed of cases of pneumonia of unknown cause in Wuhan City, China. A novel coronavirus was identified as the cause by Chinese authorities on January 7, 2020 and was provisionally named "2019-nCoV". This new Coronavirus causes a clinical picture which has received now the name COVID-19. The virus has spread subsequently worldwide and was explained on the 11th of March, 2020 by the World Health Organization to the pandemic.


2018 ◽  
Vol 24 (10) ◽  
pp. 1138-1147
Author(s):  
Bruno Rivas-Santiago ◽  
Flor Torres-Juarez

Tuberculosis is an ancient disease that has become a serious public health issue in recent years, although increasing incidence has been controlled, deaths caused by Mycobacterium tuberculosis have been accentuated due to the emerging of multi-drug resistant strains and the comorbidity with diabetes mellitus and HIV. This situation is threatening the goals of World Health Organization (WHO) to eradicate tuberculosis in 2035. WHO has called for the creation of new drugs as an alternative for the treatment of pulmonary tuberculosis, among the plausible molecules that can be used are the Antimicrobial Peptides (AMPs). These peptides have demonstrated remarkable efficacy to kill mycobacteria in vitro and in vivo in experimental models, nevertheless, these peptides not only have antimicrobial activity but also have a wide variety of functions such as angiogenesis, wound healing, immunomodulation and other well-described roles into the human physiology. Therapeutic strategies for tuberculosis using AMPs must be well thought prior to their clinical use; evaluating comorbidities, family history and risk factors to other diseases, since the wide function of AMPs, they could lead to collateral undesirable effects.


2020 ◽  
Vol 14 (2) ◽  
pp. 134-144 ◽  
Author(s):  
Matthew P. Ameh ◽  
Mamman Mohammed ◽  
Yusuf P. Ofemile ◽  
Magaji G. Mohammed ◽  
Ada Gabriel ◽  
...  

Background: The World Health Organization included snakebite envenomation among Neglected Tropical Diseases in 2017. The importance of natural products from plants is enormous, given that most prescribed drugs originate from plants. Among this is Mucuna pruriens and Mimosa pudica, with many registered patents asserting their health benefits. Objective: This study investigated the in vitro neutralizing effects of Mucuna pruriens seed and Mimosa pudica root extracts on venoms of Naja nigricollis and Bitis arietans. Methods: In mice, the LD50 and phytochemical analysis of M. pruriens and M. pudica plant extracts were carried out prior to the evaluation of their haemolytic and fibrinolytic effect. Their effects on the activities of phospholipase A2 (PLA2) were also assessed. Results: At a concentration of 50 mg/ml, both plant extracts were found to neutralize the fibrinolytic activity of N. nigricollis, but 400 mg/ml was required to neutralize the fibrinolytic activity of B. arietans. In haemolytic studies, 50 mg/ml concentration of M. pruriens extract suppressed haemolysis caused by N. nigricollis venom by 70% but at the same concentration, M. pudica extract reduced haemolysis by 49.4%. M. pruriens, at 50 mg/ml concentration, only inhibited phospholipase A2 activity by 7.7% but higher concentrations up to 400mg/ml had no effect against the venom of N. nigricollis; at 200 mg/ml. M. pudica extract inhibited PLA2 activity by 23%. Conclusion: The results suggest that M. pruriens and M. pudica may be considered as promising antivenom agents for people living in a snake-bite prone environment.


Author(s):  
Damián Muruzabal ◽  
Julen Sanz-Serrano ◽  
Sylvie Sauvaigo ◽  
Bertrand Treillard ◽  
Ann-Karin Olsen ◽  
...  

AbstractMechanistic toxicology is gaining weight for human health risk assessment. Different mechanistic assays are available, such as the comet assay, which detects DNA damage at the level of individual cells. However, the conventional alkaline version only detects strand breaks and alkali-labile sites. We have validated two modifications of the in vitro assay to generate mechanistic information: (1) use of DNA-repair enzymes (i.e., formamidopyrimidine DNA glycosylase, endonuclease III, human 8-oxoguanine DNA glycosylase I and human alkyladenine DNA glycosylase) for detection of oxidized and alkylated bases as well as (2) a modification for detecting cross-links. Seven genotoxicants with different mechanisms of action (potassium bromate, methyl methanesulfonate, ethyl methanesulfonate, hydrogen peroxide, cisplatin, mitomycin C, and benzo[a]pyrene diol epoxide), as well as a non-genotoxic compound (dimethyl sulfoxide) and a cytotoxic compound (Triton X-100) were tested on TK-6 cells. We were able to detect with high sensitivity and clearly differentiate oxidizing, alkylating and cross-linking agents. These modifications of the comet assay significantly increase its sensitivity and its specificity towards DNA lesions, providing mechanistic information regarding the type of damage.


2009 ◽  
Vol 6 (4) ◽  
pp. 453-456 ◽  
Author(s):  
Mohammed A. Alshawsh ◽  
Ramzi A. Mothana ◽  
Hassan A. Al-shamahy ◽  
Salah F. Alsllami ◽  
Ulrike Lindequist

Developing countries, where malaria is one of the most prevalent diseases, still rely on traditional medicine as a source for the treatment of this disease. In the present study, six selected plants (Acalypha fruticosa,Azadirachta indica,Cissus rotundifolia,Echium rauwalfii,Dendrosicyos socotranaandBoswellia elongata) commonly used in Yemen by traditional healers for the treatment of malaria as well as other diseases, were collected from different localities of Yemen, dried and extracted with methanol and water successfully. The antiplasmodial activity of the extracts was evaluated against fresh clinical isolates ofPlasmodium falciparum. The selectivity parameters to evaluate the efficacy of these medicinal plants were measured byin vitromicro test (Mark III) according to World Health Organization (WHO) 1996 & WHO 2001 protocols of antimalarial drug tests. Among the investigated 12 extracts, three were found to have significant antiplasmodial activity with IC50values less than 4 µg/ml, namely the water extracts ofA. fruticosa,A. indicaandD. socotrana. Six extracts showed moderate activity with IC50values ranging from 10 to 30 µg/ml and three appeared to be inactive with IC50values more than 30 µg/ml. In addition, preliminary phytochemical screening of the methanolic and aqueous extracts indicated the presence of saponins, tannins, flavonoids, terpenoids, polysaccharides and peptides.


2018 ◽  
Vol 24 (5) ◽  
pp. 576-594 ◽  
Author(s):  
Josivan da Silva Costa ◽  
Karina da Silva Lopes Costa ◽  
Josiane Viana Cruz ◽  
Ryan da Silva Ramos ◽  
Luciane Barros Silva ◽  
...  

About 132 thousand cases of melanoma (more severe type of skin cancer) were registered in 2014 according to the World Health Organization. This type of cancer significantly affects the quality of life of individuals. Caffeine has shown potential inhibitory effect against epithelial cancer. In this study, it was proposed to obtain new caffeine-based molecules with potential epithelial anticancer activity. For this, a training set of 21 molecules was used for pharmacophore perception procedures. Multiple linear regression analyses were used to propose mono-, bi-, tri-, and tetra-parametric models applied in the prediction of the activity. The generated pharmacophore was used to select 350 molecules available at the ZINCpharmer server, followed by reduction to 24 molecules, after selection using the Tanimoto index, yielding 10 molecules after final selection by predicted activity values > 1.5229. These ten molecules had better pharmacokinetic properties than the other ones used as reference and within the clinically significant limits. Only two molecules show minor hits of toxicity and were submitted to molecular docking procedures, showing BFE (binding free energy) values lower than the reference values. Statistical analyses indicated strong negative correlations between BFE and pharmacophoric properties (high influence on BFE lowering) and practically null correlation between BFE and BBB. The two most promising molecules can be indicated as candidates for further in vitro and in vivo analyzes.


Author(s):  
Elliot P. Cowan

Observation: Outbreak situations require in vitro diagnostics (IVDs) to identify those who are infected and to track the infectious agent in the population. However, such IVDs are typically not available and must be developed. In addition, the process of IVD development, assessment, and implementation are very time and resource intensive. Recognising the extraordinary public health need for IVDs in an outbreak situation, streamlined processes are needed to provide tests that meet the standard of a reasonable assurance of safety and effectiveness in the shortest amount of time. These IVDs are designated for outbreak use.Addressing Issues: This paper presents a pathway to the outbreak use of IVDs that can be considered by countries experiencing an outbreak situation. It takes into account recognition of the outbreak, product development, regulatory evaluation, implementation, and monitoring of the outbreak-use test. Streamlined assessment programmes for emergency-use tests have been established by the US Food and Drug Administration and the World Health Organization. These programmes take into account test requirements for the country in which the outbreak exists. Therefore, countries can consider adopting these tests without the need to conduct expensive and time consuming assessments, such as performance studies. Key responsible parties are identified for each step of the pathway, recognising that transparency and communication among all parties are critical.


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