Toxicological Studies of Czech Beers and Their Constituents
Abstract
:1. Introduction
- −
- The fruit fly D. melanogaster shows a consistent similarity to humans as approximately 75% of the genes involved in diseases are similar in the fly [18,19]. This well-known eukaryote with the largest scientific history in genetics has also contributed to the understanding of developmental biology, evolutionary concepts and more recently, toxicology [20,21,22,23,24]. Its short life cycle (10–12 days), cost efficiency and easy maintenance are characteristics that make Drosophila to be considered as an ideal model organism.
- −
- The HL-60 human model cell line originated thirty two years ago from a patient with acute myeloid leukaemia [25]. After culturing peripheral blood leukocytes from this female patient, a growth-factor-independent immortal cell line with distinct myeloid characteristics was obtained [26]. This promyelocytic leukaemia cell line has been used world-wide for many toxicity and cancer purposes.
2. Materials and Methods
2.1. Samples Preparation and Sample Compounds
2.2. In Vivo Animal Model and In Vitro Cellular Culture Used
2.2.1. Drosophila Melanogaster
- −
- mwh/mwh: Carries a recessive mutation mwh (multiple wing hairs) which produces several tricomas instead of one per cell when it is in homozygosis [30].
- −
- flr3/In (3LR) TM3, rippsep bx34eesBdS: Carries a flr3 (flare) marker which is a recessive lethal mutation when it is in homozygosis producing deformed tricomas, though it is viable in homozygous somatic cells if and when the larvae start the development [31].
2.2.2. HL-60 Cell Cultures
2.3. Safety In Vivo Assays of Freeze-Dried Samples
2.3.1. Toxicity
2.3.2. Genotoxicity
2.4. Protection In Vivo Tests
2.4.1. Antitoxicity
2.4.2. Antigenotoxicity
2.4.3. Longevity
2.5. Chemopreventive In Vitro Tests
2.5.1. Cytotoxicity Assay
2.5.2. Tumour Cells DNA Damage Evaluation
DNA Fragmentation
Comet Assay
Methylation Status Evaluation
3. Results and Discussion
3.1. Safety of Freeze-Dried Samples
3.2. Genotoxicity of Freeze-Dried Samples
3.3. Antitoxicity
3.4. Antigenotoxicity
3.5. Longevity
3.6. Cytotoxicity
3.7. DNA Fragmentation
3.8. Comet Assay
3.9. Methylation Status
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Beer Trade Mark | Named in the Manuscript | Beer Type/Ingredient Origin |
---|---|---|
Pilsner Urquell | Pilsner Urquell | Blond |
Staropramen Lezak | Staropramen Lezak | Blond |
Staropramen Cerny Lezak | Staropramen Cerny | Stout |
Staropramen Nealko | Staropramen Nealko | Alcohol-free |
Staropramen Nefiltrovany | Staropramen Nefiltrovany | Blond |
Lobkowicz Lezak Premium | Lobkowicz Lezak | Blond |
Lobkowicz Cerny Premium | Lobkowicz Cerny | Stout |
Lobkowicz Nealkoholicky Premium | Lobkowicz Nealko | Alcohol-free |
Lobkowicz Psenicny Premium | Lobkowicz Psenicny | Wheat |
Budweiser Budvar B:Original, Svetly lezak | Budweiser Lezak | Blond |
Budweiser Budvar B:Free, Nealkoholicke pivo | Budweiser Nealko | Alcohol-free |
Budweiser Budvar B:Cherry, Tmavy lezak s visni | Budweiser Cherry | Cherry flavoured |
Herold Svétly Breznicky Lezak | Herold Lezak | Blond |
Herold Tmave Speciálni Pivo | Herold Cerny | Stout |
Herold Psenicny Kvasnicovy Lezak | Herold Psenicny | Wheat |
Herold Polotmave Specialni Pivo | Herold Polotmave | Pomegranate flavoured |
Rest of mash (1) | Rest of mash | CULS (8) Prague brewery |
Blond malt | Blond malt | CULS Prague brewery |
Dark malt | Dark malt | CULS Prague brewery |
Sladek hop (2) | Sladek hop | CULS Prague brewery |
Saazer hop (3) | Saazer hop | CULS Prague brewery |
Saccharomyces uvarum(4) | S. uvarum | CULS Prague brewery |
Wort (5) | Wort | CULS Prague brewery |
Hopped wort (6) | Hopped wort | CULS Prague brewery |
Young beer (7) | Young beer | CULS Prague brewery |
Reaction ID | GenBank Number | Amplicon Start | Amplicon End | Forward Primer Sequence 5′ to 3′ (N) | Reverse Primer Sequence 5′ to 3′ (N) | GC-Content (%) | |
---|---|---|---|---|---|---|---|
Forward Reverse | |||||||
Alu C4 | Consensus Sequence | 1 | 98 | GGTTAGGTATAGTGGTTTATATTTGTAATTTTAGTA (36) | ATTAACTAAACTAATCTTAAACTCCTAACCTCA (33) | 25 | 27.3 |
Alu M1 | Y07755 | 5059 | 5164 | ATTATGTTAGTTAGGATGGTTTCGATTTT (29) | CAATCGACCGAACGCGA (17) | 27.6 | 58.8 |
LINE-1 | X52235 | 251 | 331 | GGACGTATTTGGAAAATCGGG (21) | AATCTCGCGATACGCCGTT (19) | 47.6 | 52.6 |
Sat-α | M38468 | 139 | 260 | TGATGGAGTATTTTTAAAATATACGTTTTGTAGT (34) | AATTCTAAAAATATTCCTCTTCAATTACGTAAA (33) | 23.5 | 21.2 |
Compound | Clones per Wing (nº Spots) (1) | |||||
---|---|---|---|---|---|---|
N° of Wings | Small Single Clones (1–2 Cells) m = 2 | Large Simple Clones (>2 Cells) m = 5 | Twin Clones m = 5 | Total Clones m = 2 | U-Test (2) | |
H2O | 38 | 0.105 (4) | 0.053 (2) | 0 | 0.158 (6) | |
H2O2 | 40 | 0.2 (8) | 0.2 (8) | 0 | 0.400 (16) + | |
Pilsner Urquell (mg/mL) | ||||||
3.125 | 40 | 0.175 (7) | 0.100 (4) | 0 | 0.275 (11) i | ∆ |
50 | 40 | 0.225 (9) | 0.075 (3) | 0 | 0.300 (12) i | ∆ |
Blond malt (mg/mL) | ||||||
0.0625 | 40 | 0.225 (9) | 0.025 (1) | 0 | 0.250 (10) i | ∆ |
1 | 40 | 0.250 (10) | 0.075 (3) | 0 | 0.325 (13) i | ∆ |
Dark malt (mg/mL) | ||||||
0.0625 | 40 | 0.200 (8) | 0.025 (1) | 0 | 0.225 (9) i | ∆ |
1 | 40 | 0.100 (4) | 0.025 (1) | 0 | 0.125 (5) i | ∆ |
Sladek hop (mg/mL) | ||||||
0.00156 | 40 | 0.125 (5) | 0.05 (2) | 0 | 0.175 (7) i | ∆ |
0.025 | 38 | 0.316 (12) | 0.052 (2) | 0 | 0.368 (14) i | ∆ |
Saazer hop (mg/mL) | ||||||
0.000625 | 38 | 0.211 (8) | 0.052 (2) | 0 | 0.263 (10) i | ∆ |
0.01 | 38 | 0.131 (5) | 0.079 (3) | 0 | 0.210 (8) i | ∆ |
S. uvarum (mg/mL) | ||||||
0.00023 | 40 | 0.200 (8) | 0.075 (3) | 0 | 0.275 (11) i | ∆ |
0.00375 | 34 | 0.294 (10) | 0.059 (2) | 0 | 0.353 (12) i | ∆ |
Wort (mg/mL) | ||||||
3.125 | 40 | 0.300 (12) | 0 | 0.025 (1) | 0.325 (13) i | ∆ |
50 | 38 | 0.132 (5) | 0.026 (1) | 0 | 0.158 (6) i | ∆ |
Hopped wort (mg/mL) | ||||||
3.125 | 40 | 0.200 (8) | 0.025 (1) | 0 | 0.225 (9) i | ∆ |
50 | 38 | 0.131 (5) | 0.158 (6) | 0 | 0.289 (11) i | ∆ |
Young beer (mg/mL) | ||||||
3.125 | 40 | 0.255 (9) | 0 | 0 | 0.255 (9) i | ∆ |
50 | 34 | 0.353 (12) | 0 | 0 | 0.353 (12) i | ∆ |
Clones per Wing (nº Spots) (1) | Mann Whitney U-Test (2) | Inhibition Percentage (%) (3) | |||||
---|---|---|---|---|---|---|---|
Compound | N° of Wings | Small Single Clones (1–2 Cells) m = 2 | Large Simple Clones (More Than 2 Cells) m = 5 | Twin Clones m = 5 | Total Clones m = 2 | ||
H2O | 40 | 0.175 (7) | 0 | 0 | 0.175 (7) | ||
H2O2 | 40 | 0.2 (8) | 0.2 (8) | 0 | 0.400 (16) + | ||
Pilsner Urquell (mg/mL) | |||||||
3.125 | 38 | 0.263 (10) | 0.026 (1) | 0 | 0.289 (11) β | 27.75 | |
50 | 40 | 0.200 (8) | 0.025 (1) | 0 | 0.225 (9) β | 43.75 | |
Blond malt (mg/mL) | |||||||
0.0625 | 40 | 0.225 (9) | 0.050 (2) | 0 | 0.275 (11) β | 31.25 | |
1 | 38 | 0.315 (12) | 0.106 (4) | 0 | 0.421 (16) λ | ∆ | −5.25 |
Dark malt (mg/mL) | |||||||
0.0625 | 40 | 0.175 (7) | 0.05 (2) | 0 | 0.225 (9) β | 43.75 | |
1 | 38 | 0.131 (5) | 0.052 (2) | 0 | 0.183 (7) β | 54.25 | |
Sladek hop (mg/mL) | |||||||
0.00156 | 38 | 0.131 (5) | 0.079 (3) | 0 | 0.210 (8) β | 47.50 | |
0.025 | 40 | 0.325 (13) | 0.075 (3) | 0 | 0.400 (16) λ | ∆ | 0.00 |
Saazer hop (mg/mL) | |||||||
0.000625 | 38 | 0.079 (3) | 0.052 (2) | 0 | 0.131 (5) β | 67.25 | |
0.01 | 40 | 0.050 (2) | 0.050 (2) | 0 | 0.100 (4) β | 75.00 | |
S. uvarum (mg/mL) | |||||||
0.00023 | 18 | 0.278 (5) | 0.222 (4) | 0 | 0.500 (9) λ | ∆ | −25.00 |
0.00375 | 27 | 0.222 (6) | 0.125 (3) | 0 | 0.333 (9) β | 16.75 | |
Wort (mg/mL) | |||||||
3.125 | 40 | 0.125 (5) | 0.025 (1) | 0 | 0.150 (6) β | 62.50 | |
50 | 40 | 0.250 (10) | 0.025 (1) | 0 | 0.275 (11) β | 31.25 | |
Hopped wort (mg/mL) | |||||||
3.125 | 40 | 0.325 (13) | 0.075 (3) | 0 | 0.400 (16) λ | ∆ | 00.00 |
50 | 40 | 0.100 (4) | 0.100 (4) | 0 | 0.200 (8) β | 50.00 | |
Young beer (mg/mL) | |||||||
3.125 | 40 | 0.425 (17) | 0.075 (3) | 0 | 0.500 (20) λ | ∆ | −25.00 |
50 | 26 | 0.500 (13) | 0.192 (5) | 0 | 0.692 (18) λ | ∆ | −73.00 |
Compound | Concentration | Mean Lifespan (1) (Days) | Mean Healthspan (1) (Days) | ||
---|---|---|---|---|---|
Pilsner Urquell | Control | 74.319 | 47.048 | ||
3.125 mg/mL | 69.096 | * | 48.615 | ns | |
6.25 mg/mL | 73.179 | ns | 45.385 | ns | |
12.5 mg/mL | 74.571 | ns | 57.923 | * | |
25 mg/mL | 64.857 | * | 44.765 | ns | |
50 mg/mL | 72.413 | ns | 49.462 | ns | |
Blond malt | Control | 69.888 | 35.959 | ||
0.0625 mg/mL | 76.349 | * | 47.769 | * | |
0.125 mg/mL | 70.412 | ns | 39.714 | ns | |
0.25 mg/mL | 78.448 | ns | 65.617 | * | |
0.5 mg/mL | 73.514 | ns | 48.067 | * | |
1 mg/mL | 77.946 | * | 53.583 | * | |
Dark malt | Control | 69.888 | 35.959 | ||
0.0625 mg/mL | 70.557 | ns | 50.129 | * | |
0.125 mg/mL | 66.314 | * | 34.135 | ns | |
0.25 mg/mL | 58.281 | * | 35.692 | ns | |
0.5 mg/mL | 73.077 | ns | 44.001 | ns | |
1 mg/mL | 72.433 | ns | 38.176 | ns | |
Sladek hop | Control | 72.107 | 44.211 | ||
0.00156 mg/mL | 77.439 | * | 50.792 | ns | |
0.00312 mg/mL | 78.083 | * | 54.987 | * | |
0.00625 mg/mL | 68.774 | ns | 45.750 | ns | |
0.0125 mg/mL | 68.280 | ns | 42.154 | ns | |
0.025 mg/mL | 67.556 | ns | 36.667 | * | |
Saazer hop | Control | 72.107 | 44.211 | ||
0.000625 mg/mL | 60.714 | * | 29.929 | * | |
0.00125 mg/mL | 69.993 | ns | 43.947 | ns | |
0.0025 mg/mL | 70.314 | ns | 48.909 | ns | |
0.005 mg/mL | 70.143 | ns | 44.754 | ns | |
0.01 mg/mL | 72.098 | ns | 53.091 | * | |
S. uvarum | Control | 74.319 | 47.048 | ||
0.00023 mg/mL | 67.590 | * | 42.545 | * | |
0.00047 mg/mL | 73.738 | ns | 53.167 | ns | |
0.00094 mg/mL | 71.876 | ns | 51.533 | * | |
0.00187 mg/mL | 73.223 | ns | 55.292 | * | |
0.00375 mg/mL | 79.060 | * | 54.393 | * | |
Wort | Control | 74.319 | 47.048 | ||
3.125 mg/mL | 66.179 | * | 51.929 | ns | |
6.25 mg/mL | 68.399 | ns | 38.143 | * | |
12.5 mg/mL | 77.628 | ns | 64.238 | * | |
25 mg/mL | 67.464 | * | 52.571 | ns | |
50 mg/mL | 63.885 | * | 48.250 | ns | |
Hopped wort | Control | 74.319 | 47.048 | ||
3.125 mg/mL | 72.232 | ns | 50.077 | ns | |
6.25 mg/mL | 76.922 | ns | 63.375 | * | |
12.5 mg/mL | 66.256 | * | 41.167 | ns | |
25 mg/mL | 71.095 | ns | 40.541 | * | |
50 mg/mL | 73.004 | ns | 53.833 | ns | |
Young beer | Control | 74.319 | 47.048 | ||
3.125 mg/mL | 71.696 | ns | 47.357 | ns | |
6.25 mg/mL | 70.747 | * | 57.357 | * | |
12.5 mg/mL | 72.117 | * | 52.224 | * | |
25 mg/mL | 78.426 | ns | 57.786 | * | |
50 mg/mL | 75.314 | ns | 58.314 | * |
© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
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Merinas-Amo, T.; Merinas-Amo, R.; García-Zorrilla, V.; Velasco-Ruiz, A.; Chladek, L.; Plachy, V.; del Río-Celestino, M.; Font, R.; Kokoska, L.; Alonso-Moraga, Á. Toxicological Studies of Czech Beers and Their Constituents. Foods 2019, 8, 328. https://doi.org/10.3390/foods8080328
Merinas-Amo T, Merinas-Amo R, García-Zorrilla V, Velasco-Ruiz A, Chladek L, Plachy V, del Río-Celestino M, Font R, Kokoska L, Alonso-Moraga Á. Toxicological Studies of Czech Beers and Their Constituents. Foods. 2019; 8(8):328. https://doi.org/10.3390/foods8080328
Chicago/Turabian StyleMerinas-Amo, Tania, Rocío Merinas-Amo, Victoria García-Zorrilla, Alejandro Velasco-Ruiz, Ladislav Chladek, Vladimir Plachy, Mercedes del Río-Celestino, Rafael Font, Ladislav Kokoska, and Ángeles Alonso-Moraga. 2019. "Toxicological Studies of Czech Beers and Their Constituents" Foods 8, no. 8: 328. https://doi.org/10.3390/foods8080328