Catequinas del té verde: efectos antigenotóxicos y genotóxicos. Revisión sistemática / Green tea catechins: antigenotoxic and genotoxic effects. Systematic review

Las catequinas del té verde (Camellia sinensis) (CTV) presentan efectos benéficos para la salud asociados a su potencial antioxidante. Por otra parte, el estrés oxidante es una de las vías de inducción de daño genotóxico. De ahí que, en la presente revisión se realizó un análisis de los efectos antigenotóxicos y genotóxicos de las CTV, haciendo énfasis en las vías implicadas en estos procesos y sus efectos en la salud. Se realizó una revisión de artículos indexados en las bases de datos de PubMed® y Science Direct® (2021) con las palabras clave "green tea" y "green tea catechins". Se delimitaron los estudios utilizando los operadores booleanos "AND", "OR" y "NOT" ("antigenotoxic", "genotoxic", "antioxidant" y "prooxidant"). En su mayoría se consideraron las publicaciones del 2016 al 2021. Se observó que los efectos benéficos en la salud de las CTV están relacionados con: a) su actividad antioxidante mediante la captura, inhibición y prevención de la formación de las especies reactivas de oxígeno; b) la regulación del sistema antioxidante endógeno; c) la activación de los mecanismos de reparación al contribuir en la eliminación del aducto 8-hidroxi-2'-desoxiguanosina; d) la inducción de apoptosis en células con daño al ADN; y e) la inhibición de la inflamación relacionada con su actividad antiapoptótica. Si bien, en algunos de los estudios se reportaron efectos genotóxicos, estos a su vez contribuyeron en la eliminación de células con daño genético, por lo que, no se puede considerar del todo a la actividad genotóxica de las CTV como perjudiciales para la salud(AU)

The green tea catechins (Camellia sinensis) (CTV) have beneficial effects for health associated with their antioxidant potential. Moreover, oxidative stress is one of the pathways for inducing genotoxic damage. Hence, in this review, an analysis of the antigenotoxic and genotoxic effects of CTV was carried out, emphasizing the pathways involved in these processes and their effects on health. A review of articles indexed in the PubMed® and ScienceDirect® (2021) databases with the keywords "green tea" and "green tea catechins" was carried out. Studies were delimited using the Boolean operators "AND", "OR" and "NOT" ("antigenotoxic", "genotoxic", "antioxidant" and "prooxidant"). For the most part, publications from 2016 to 2021 were considered. It was observed that the beneficial health effects of CTVs are related to: a) their antioxidant activity through the capture, inhibition and prevention of the formation of reactive oxygen species; b) the regulation of the endogenous antioxidant system; c) the activation of the repair mechanisms by contributing to the elimination of the 8-hydroxy-2'-deoxyguanosine adduct; d) the induction of apoptosis in cells with DNA damage; and e) the inhibition of inflammation related to its antiapoptotic activity. Although some of the studies reported genotoxic effects, these in turn contributed to the elimination of cells with genetic damage. Therefore, the genotoxic activity of CTV cannot be considered as harmful to health

Antioxidant and antigenotoxic properties of Alpinia galanga, Curcuma amada, and Curcuma caesia

Objective: To compare the antioxidant and anti-genotoxic properties of Alpinia (A.) galanga, Curcuma (C.) amada, and C. caesia. Methods: Cytotoxicity of ethanolic extracts of A. galanga, C. amada, and C. caesia at selected doses was evaluated by trypan blue, MTT, and flow cytometry-based assays. Genotoxicity and anti-genotoxicity (against methyl methanesulfonate, 35 μM and H2O2, 250 μM) of these plants were studied by comet assay in human lymphocytes in vitro. Furthermore, DPPH, ABTS, FRAP, lipid peroxidation, and hydroxyl radical scavenging assays were performed to study the antioxidant potentials of the plants. Finally, anti-genotoxic potential of C. amada was validated in Swiss albino mice using comet assay. Phytochemical composition of C. amada was determined by GC/MS and HPLC. Results: The selected doses (2.5, 5, and 10 μg/mL) of A. galanga, C. amada, and C. caesia were non-toxic by cytotoxicity tests. All three ethanolic extracts of plant rhizomes demonstrated antioxidant and anti-genotoxic properties against methyl methanesulfonate-and H2O2-induced oxidative stress in human peripheral blood lymphocytes in vitro. Multivariate analysis revealed that various antioxidant properties of these extracts in DPPH, ABTS, and FRAP assays were strongly correlated with their total phenolic constituents. C. amada extract conferred protection against cyclophosphamide-induced DNA damage in the bone marrow cells of mice and DNA damage was significantly inhibited by 2.5 mg/kg C. amada extract. Conclusions: C. amada is rich in potentially bioactive molecules and exhibits potent antioxidant activities. Its anti-genotoxicity against cyclophosphamide-induced oxidative stress is also confirmed in this study.

Comparative Study between Powder and Nanoparticles of Dried Cactus (Opuntia ficus-indica L.) Fruit Peels in Streptozotocin-induced Diabetic Rats: Anti-microbial and Anti-genotoxic Capacity

Aim: To overcome the toxic effects attributed to the use medicinal treatments against diabetes there is a desire toward using natural food and folk remedies. So, the aim this study was to use nanoparticles of dried cactus fruit peels (Opuntia ficus-indica) compared with powder materials to control blood glucose in streptozotocin (STZ)-induced diabetic rats. Place and Duration of Study: Food Toxicology and Contaminants Department, Polymer and Pigments Department, and Cell Biology Department, National Research Centre, Egypt, between April 2017 and March 2018. Methodology: Powder and nanoparticles were used to determine the fatty acids content and assessment the dietary fiber contents, mycotoxin contamination as well as examine the antimicrobial activity. Moreover, male albino rats were treated with single i.p. dose of STZ to induce diabetes. STZ induced-rats were divided into several groups and treated daily with 50, 100 and 200 mg/kg b.wt of cactus fruit peels powder or nanoparticles orally for 2 months. At the end of the experimental period, blood samples were aspirated to determine glucose levels as well as liver and pancreas tissues were collected for the biological analyses. Results: The results of the present study exhibited that both extracts of cactus fruit peels either powder or nanoparticles were able to reduce significantly the glucose levels and increase the expression of insulin and insulin receptor genes in induced-diabetic rats. Moreover, cactus fruit peels extracts exhibited antifungal and antibacterial activities and increase in the antioxidant enzymes (GPx and CAT) as well as anti-genotoxic effects in DM-induced rats. Furthermore, nanoparticles of dried cactus fruit peels were more effective in control glucose levels, gene expression, antimicrobial and anti-genotoxic activities compared with powder materials even in its low dose. Conclusion: The results conclude that the nanoparticles form of cactus fruit peels extracts was much more effective in the therapeutic action than powder form. The anti-diabetic effect of cactus fruit peels nanoparticles could be attributed to its content from dietary fiber. Moreover, the antifungal and antibacterial activities as well as the anti-genotoxic ability of cactus fruit peels nanoparticles could be attributed to fatty acids and/or GABA contents which were more able to control oxidative stress.

Antigenotoxicity protection of Carapa guianensis oil against mitomycin C and cyclophosphamide in mouse bone marrow

ABSTRACT The aim of this study was to evaluate the possible protective of C. guianensis oil against MMC and CP, which are direct- and indirect-acting chemical mutagens, using the micronucleus test. Three experiments were performed. First the C. guianensis oil was co-administered to mice at doses of 250, 500 and 1000 mg/kg bw with 4 mg/kg bw MMC or 50 mg/kg bw CP. Second, the mutagenic drug (CP) was administered ip 50 mg/kg bw and after 6 and 12 hours 250 and 500 mg/kg bw of C. guianensis oil were administered. In the last, C. guianensis oil was administrated (250 and 500 mg/kg bw) during five days and after it was administered ip 50 mg/kg bw CP. The results obtained showed that the C. guianensis oil is not cytotoxic neither genotoxic to mouse bone marrow. Regarding the antimutagenic effect, all doses of C. guianensis oil were significantly (p < 0.05) effective in reducing the frequency of micronucleated polychromatic erythrocytes, when compared with MMC or CP alone. Based on these results, our results suggest that the C. guianensis oil shows medicinal potential as an antimutagenic agent, modulating the mutagenicity caused by both direct- and indirect-acting chemical mutagens, in a mammalian model.

Isolation and characterization of flavanols from Anthocephalus cadamba and evaluation of their antioxidant, antigenotoxic, cytotoxic and COX-2 inhibitory activities

ABSTRACT In search of lead molecules for use in disease prevention and as food additive from natural sources, two flavanols were isolated from leaves of Anthocephalus cadamba (Roxb.) Miq., Rubiaceae. Their structures were established as 6-hydroxycoumarin-(4"→8)-(-)-epicatechin and 6-hydroxycoumarin-(4"→8)-(-)-epicatechin-(4→6‴)-(-)-epicatechin on the basis of spectroscopic data. Both the compounds exhibited potent antioxidant and antigenotoxic activity. 6-Hydroxycoumarin-(4"→8)-(-)-epicatechin scavenged DPPH, ABTS+.and superoxide anion radicals with IC50 values of 6.09 µg/ml, 5.95 µg/ml and 42.70 µg/ml respectively whereas the IC50 values for 6-hydroxycoumarin-(4"→8)-(-)-epicatechin-(4→6‴)-(-)-epicatechin were 6.62 µg/ml for DPPH free radicals, 6.93 µg/ml for ABTS radical cations and 49.08 µg/ml for superoxide anion radicals. Both the compounds also exhibited potent reducing potential in reducing power assay and protected the plasmid DNA (pBR322) against the attack of hydroxyl radicals generated by Fenton's reagent in DNA protection assay. In SOS chromotest, 6-hydroxycoumarin-(4"→8)-(-)-epicatechin decreased the induction factor induced by 4NQO (20 µg/ml) and aflatoxin B1 (20 µg/ml) by 31.78% and 65.04% respectively at a concentration of 1000 µg/ml. On the other hand, 6-hydroxycoumarin-(4"→8)-(-)-epicatechin-(4→6‴)-(-)-epicatechin decreased the genotoxicity of these mutagens by 37.11% and 47.05% respectively. It also showed cytotoxicity in COLO-205 cancer cell line with GI50 of 435.71 µg/ml. Both the compounds showed moderate cyclooxygenase-2 inhibitory activity.

Protective effect of Genistein against N-nitrosodiethylamine (NDEA)-induced hepatotoxicity in Swiss albino rats / 药物分析学报

In the present study, we studied the effect of Genistein against the hepatotoxicity induced by N-nitrosodiethylamine (NDEA). NDEA is present in almost all kinds of food stuff and has been reported to be a hepatocarcinogen. The male rats were exposed to NDEA (0.1 mg/mL) dissolved in drinking water separately and along with 25, 50, 100 mg/mL of Genistein for 21 days. The activities of serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) were measured in blood serum. Lipid peroxidation, protein carbonyl content, micronucleus frequency and DNA damage (Comet assay) were performed on rat hepatocytes. The results of the study reveal that the treatment of NDEA along with Genistein showed a significant dose-dependent decrease in the levels of blood serum enzymes i.e., SGOT, SGPT, ALP and LDH (Po0.05). The HE staining of histological sections of the liver also revealed a protective effect of Genistein. A significant dose-dependent reduction in the lipid peroxidation and protein carbonyl content was observed in rats exposed to NDEA (0.1 mg/mL) along with Genistein (Po0.05). The results obtained for the comet assay in rat hepatocytes showed a significant dose-dependent decrease in the mean tail length (Po0.05). Thus the present study supports the hepatoprotective role of Genistein.

The antigenotoxic activity of latex from Himatanthus articulatus

Himatanthus articulatus (Vahl) Woodson (Apocynaceae) is a native plant to the Amazon popularly used to treat ulcers, tumors, inflammations, cancer, syphilis and malaria. The aim of the present study was to investigate the in vivo genotoxic/antigenotoxic and mutagenic potential of this plant, using the comet and the micronucleus assays in mice. Female and male adult mice were treated with different doses of H. articulatus latex by gavage for two consecutive days. For the experiments, the latex was serially diluted with water to 1:2 (D1); 1:4 (D½) and 1:8 (D») and administered to the animals. The blood slides were exposed to hydrogen peroxide (ex vivo) to evaluate antigenotoxic effect. Under the experimental conditions used in this study, the latex of H. articulatus did not increase the frequency of DNA damage as measured by the comet assay and micronucleus test in treated mice, indicating a non-genotoxic and non-mutagenic activity. In relation to the antigenotoxicity, latex exerted protective effect against DNA damage induced by hydrogen peroxide. Therefore, our results add new information about the antigenotoxic potential of H. articulatus latex, which is popularly used in the Amazon to treat different pathologies.

Chemopreventive activity of phenylalanine against damage mutagenic prompted by the acute administration of cyclophosphamide in pregnant and non-pregnant mice using the micronucleus test / Atividade quimiopreventiva da fenilalanina contra danos mutagênicos pela administração aguda de ciclofosfamida em ratas grávidas e não grávidas, utilizando o teste do micronúcleo

This study aimed to evaluate the quimiopreventive ability of phenylalanine. We used pregnant and non-pregnant female mice divided into the following groups: G1-PBS, (0.1 mL/kg b.w); G2, cyclophosphamide (35 mg/kg p.c.-i.p.); G3 and G4, phenylalanine (150 and 300 mg/kg b.w respectively-v.o.) and G5 and G6, association between the two doses of phenylalanine and cyclophosphamide, respectively. The peripheral blood samples were taken at T0, before the administration of any drug test and / or vehicles, also at T24 and T48 where the collections were made 24 and 48 h after administration of cyclophosphamide, respectively. A general analysis has found that, for the group of non-pregnant female, the antimutagenic evaluation showed reduction percentages of damage of 57.24 percent and 31.64 percent for G5 and G6, respectively, at T24, and 29.32 percent and 24.13 percent for G5 and G6, respectively, at T48. Antimutagenic pregnant animals in the 24 h quimiopreventive efficiency shown only for the lower dose (G5) and the percentages of reduction were 43.25 percent in G5 and G6 at 18.47 percent. At T48 the harm-reduction percentages were 44.67 percent and 37.76 percent for G5 and G6, respectively.

A presente pesquisa teve por objetivo avaliar a capacidade quimiopreventiva da fenilalanina. Utilizou-se um lote de fêmeas prenhes e não prenhes divididas nos seguintes grupos experimentais: G1, PBS (0,1 mL/kg p.c.); G2, ciclofosfamida (35 mg/kg p.c.-i.p.); G3, fenilalanina (150 mg/kg p.c.-v.o.) e G4, fenilalanina (300 mg/kg p.c.-v.o.) e G5 (150 mg/kg p.c. de fenilalanina e 35 mg/kg de ciclofosfamida); G6, (300 mg/kg p.c. de fenilalanina e 35 mg/kg de ciclofosfamida). As coletas de sangue periférico foram realizadas em T0, antes da administração de qualquer substância teste e/ou veículos, e igualmente em T24 e T48, onde as coletas foram realizadas respectivamente 24 e 48 h após a administração da ciclofosfamida. Em uma análise geral verificou-se que, para o grupo de fêmeas não prenhes, a avaliação da antimutagenicidade demonstrou porcentagens de redução de danos de 57,24 por cento e 31,64 por cento para G5 e G6, respectivamente, em T24, e 29,32 por cento e 24,13 por cento para G5 e G6, respectivamente, em T48. Nos animais prenhes a antimutagenicidade de 24 h demonstrou eficiência quimiopreventiva apenas para a menor dose (G5) e as porcentagens de redução de danos foram de 43,25 por cento em G5 e 18,47 por cento em G6. No momento T48 as porcentagens de redução de danos foram de 44,67 por cento e 37,76 por cento para G5 e G6, respectivamente.

Antigenotoxic activity and antioxidant properties of organic and aqueous extracts of pequi fruit (Caryocar brasiliense Camb. ) pulp

The daily consumption of natural antioxidants protects against oxidative damage caused by reactive oxygen species (ROS), including DNA damage, and can reduce the risk of cancer, atherosclerosis and other degenerative diseases. The pulp of pequi (Caryocar brasiliense Camb.) fruit, a tree native to the Brazilian savannah, contains several compounds with antioxidant properties, including carotenoids, vitamin C, phenolic compounds such as flavonoids, saponins and tannins, and essential oils. In this work, we examined the ability of organic and aqueous extracts of pequi fruit pulp to protect against the genotoxicity induced by two antineoplastic drugs, cyclophosphamide (CP) and bleomycin (BLM). Micronucleus tests with mouse bone marrow cells and single-cell gel electrophoresis (comet assay) with peripheral blood leukocytes were used to examine the effects of CP and BLM, respectively. The antioxidant activity of the extracts was assessed by measuring lipid peroxidation with the TBARS method in mouse plasma. The fruit pulp extracts had no clastogenic or genotoxic effects in the cells studied, but both extracts protected against oxidative DNA damage caused by BLM or CP, indicating an ability to inhibit chemical mutagenesis in vivo. However, the protective effect against oxidative DNA damage depended on the dose of extract used. At the doses tested, the aqueous extract enhanced lipid peroxidation in mice of both sexes, especially in males. In contrast, the organic extract enhanced lipid peroxidation only in male mice, with no significant effect in females. These results suggest that, with adequate adjustment of the dose, an organic extract of pequi fruit pulp could be a useful dietary supplement with natural antioxidant activity, at least in females.