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•Fluoroquinolones (FQ) may be degraded by different ROS.•Ionization state and fluorine atoms in FQ regulate their ROS-mediated degradation.•ROS-mediated degradation products of FQ ...were nontoxic in Vero cells.•Fluorine atoms increase FQ electron donor ability by fluoromaticity effect.
Fluoroquinolones have been attractive broad-spectrum antibiotics for ophthalmic application. However, they have shown phototoxicity as a significant side effect, which is strongly dependent on fluoroquinolone structure and some environment conditions. Beyond their photo-reactivity, an indirect light-induced process deserves to be considered. The photosensitized action of molecules present in the ocular organ, such as Riboflavin, may produce reactive oxygen species (ROS) that could degrade fluoroquinolones. As a consequence, the antibiotics may lose their therapeutic action and/or produce degradation products with harmful effects on health.
In this contribution, a kinetic analysis of ROS-mediated degradation processes of ophthalmic quinolones is addressed. Further, considering the evidence towards the structure-modulated phototoxicity, we evaluated the influence of structural fluorine atoms on these processes. The non-fluorinated precursor Nalidixic Acid and the fluoroquinolones (Ciprofloxacin, Norfloxacin and Lomefloxacin) were selected for this study. Cytotoxicity experiments in Vero cells were performed in order to investigate the potential toxicity of the ROS-mediated degradation products.
Our results suggest that quinolones may be degraded by ROS and these processes are regulated by the ionization state of quinolone and the presence of fluorine atoms in their structure. Both effects increase the electron donor ability of the quinolones, which favor electron transfer processes and increase their reactivity towards species with an electrophilic character. Interestingly, this fluorine-dominated effect has been recently called “fluoromaticity”.
Cytotoxicity assays indicated that neither the Qs nor their ROS-mediated degradation products presented injury on Vero cells under the current experimental conditions.
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•Subchronic toxicity of M. verticillata essential oil was studied.•The essential oil not induced 90-day toxicity and genotoxicity effect on Wistar rats.•The essential oil appears to ...be safe and could be devoid of any toxic risk.
Minthostachys verticillata (Lamiaceae), popularly known as peperina is largely used in popular medicine for its digestive, carminative, antispasmodic and antirheumatic properties. There are no reports of repeated exposure toxicity to guarantee their safety. The present study investigated the chemical composition, analyzed by GC–FID, and the 90-day toxicity and genotoxicity effect of M. verticillata essential oil (Mv-EO), using Wistar rats as test animals. The rats were divided into four groups (5rats/sex/group) and Mv-EO was administered on diet at doses of 0, 1, 4 and 7g/kg feed. The main components of Mv-EO were pulegone (64.65%) and menthone (23.92%). There was no mortality, adverse effects on general conditions or changes in body weight, food consumption and feed conversion efficiency throughout the study in male and female rats. Subchronic administration of Mv-EO did not alter the weights, morphological and histopathological analyses of liver, kidney and intestine. Genotoxicity was tested by micronucleus and comet assays. Mv-EO up to a concentration of 7g/kg feed for 90days did not exert a cyto-genotoxic effect on the bone marrow and cells blood of Wistar rats. These results suggest that Mv-EO appears to be safe and could be devoid of any toxic risk.
The aim of the current study was to evaluate the protective effects of Minthostachys verticillata essential oil (Mv-EO) against aflatoxin B
1
-induced toxicity in Vero cells in vitro and in male ...rats. The cytotoxicity of AFB
1
(0-30 µg/mL) and Mv-EO (0-500 µg/mL) was determined on Vero cells using the Neutral Red assays. The tested Mv-EO did not cause genotoxicity or cytotoxicity in vivo and was able to attenuate AFB
1
-caused cytotoxicity and genotoxicity. Animals were divided into four groups consisting of 5 (five) rats in each group: T1 basal feed (BF - negative control), T2 BF + Mv-EO 0.04%, T3 BF + AFB
1
100 µg/kg, T4 BF + food with AFB
1
100 µg/kg + Mv-EO 0.04%. Tissue samples were collected at the end of treatment period for genotoxic study and histological examination. Treatment with Mv-EO alone and even combined with AFB
1
showed a significant improvement in the histomorphometry of intestinal villi, without alteration of productive parameters. Also, the micronucleus test demonstrated that Mv-EO reduced AFB
1
-induced DNA damage on bone marrow cells of male Wistar rats. This study demonstrated that Mv-EO could be used as protective against AFB
1
-induced cytotoxicity and genotoxicity, and as phytogenic feed additive.
Chlorogenic acid (ChlA) has shown short-term protective effects against the cyto-genotoxic effects of ochratoxin A (OTA). The present study evaluated the effect of oral administration of ChlA in male ...Wistar rats exposed to OTA. OTA (0.4 mg/kg bw/day), ChlA (5 mg/kg bw/day), or the combination of both, were administered orally to animals during 28 days. No deaths, decrease in feed consumption or change in the body weight of animals were observed in any group. In the OTA-treated group a decrease in locomotion as well as increased DNA damage in blood, kidney and bone marrow cells were observed. ChlA alone was not genotoxic for animals. The combination of OTA+ChlA decreased the DNA damage by 37% in blood cells, by 55% in kidney cells and by 80% in bone marrow cells compared to OTA-treated group. In conclusion, oral treatment with ChlA showed a good protective effect on genotoxicity produced by OTA in rats during 28 days exposure.
► Toxicity and chemical composition of Minthostachys verticillata essential oil were studied. ► The main compounds were pulegone, menthone and limonene. ► The essential oil not induced cytotoxic ...effect both on Vero cell and human PBMCs. ► The oil not induced apoptosis on human PBMCs nor genotoxicity on erythrocytes of mice. ► The results suggest this species appears to be a safe therapeutic agent.
Minthostachys verticillata (peperina) is an aromatic and medicinal plant with several uses and ethnobotanical properties. Numerous studies have demonstrated that its essential oil (Mv-EO) presents antimicrobial capacity and shows immunomodulating and anti-allergic properties in human cell lines. Thus, the goal of this study was to investigate the main chemical composition, analyzed by GC–FID, and the cyto-genotoxic effects of Mv-EO, using Vero cells, human PBMCs and mice bone marrow cells. The Mv-EO was rich in pulegone 60.5% and menthone 18.2%. Our results clearly show that Mv-EO is not cyto-genotoxic in vitro nor in vivo. It not induced cytotoxic effects, as indicated by trypan blue dye exclusion and NRU assays both in Vero cells and human PBMCs. In addition, Mv-EO (100–1000μg/mL) not induced apoptotic effects on human PBMCs, as indicated by Hoechst staining and DNA fragmentation analysis by agarose gel electrophoresis. The in vivo assay showed that Mv-EO (25–500mg/kg) not increased the frequency of micronucleus in bone marrow cells of mice. Further, the ratio of polychromatic/normochromatic erythrocytes was not modified. These findings suggest that Mv-EO appears to be safe as a therapeutic agent.
Arachis hypogaea L. (Leguminosae) is distributed in tropical and subtropical areas. Peanut has high nutritional and commercial value. Scientific research showed that peanut has biological properties ...such as anticancer, antioxidant, antiinflammatory. However, it is necessary to know if consumption of peanut, either as food or as a phytopharmaceutical implies a health risk. The aim was to evaluate cytotoxicity and genotoxicity of ethanolic extracts from A. hypogaea. Also, chemical characterization of these extracts was performed. Cytotoxicity was evaluated by MTT and Neutral Red Uptake (NRU) assays on Vero cells. Genotoxicity was studied by Micronuclei and comet assays on Balb/C mice. Qualitative and quantitative chemical analysis of extracts were performed. Results showed that extracts have low cytotoxicity. Tegument ethanolic extract (TEE) and Seed ethanolic extract (SEE) were not genotoxic. The treatments with TEE at 250 mg/kg and SEE at 2000 mg/kg revealed (highest concentrations evaluated) some toxicity on blood marrow cells of mice. Chemical characterization indicated that TEE had 74.33 ± 1.10 mg GAE/g of dried extract and SEE had 15.05 ± 0.06 mg GAE/g of dried extract of total phenolic content. Also, proanthocyanidins (O.D. at 550 nm 1.39 ± 0.15) and caffeic acid (2.46%) were identified in TEE. While, linoleic acid (58.84%) oleic acid (11.31%) and palmitic acid (8.37%) were major compounds of SEE. In conclusion, peanut consumption is safe at concentrations recommended for healthy uses, such as nutrition, and phytomedicine.
Food science, Food safety, Natural product chemistry, Arachis hypogaea L, Cytotoxicity, Genotoxicity, Caffeic acid, Linoleic acid.
Soybean mosaic disease, caused by the soybean mosaic virus (SMV), is responsible for major losses in yield and seed quality worldwide. Although resistant cultivars are used for its prevention and ...control, an alternative strategy could consist of applying environmentally friendly antimicrobial agents, such as extracts and essential oils (EOs) of aromatic plants. This study assessed an extract of Achyrocline satureioides and EOs of Minthostachys verticillata, Origanum vulgare, and Thymus vulgaris in terms of their phytotoxicity in soybean. Since all the concentrations tested were found to be safe, the activity of each product against SMV was then assayed in vivo, i.e., in experimentally infected soybean plants. The parameters measured were plant height, wet weight, and virus titer. All the treated plants had a greater height and weight than those in the viral control group. The EOs of M. verticillata (0.80 mg/mL) and T. vulgaris (0.71 mg/mL) inhibited the production of viral antigens, as determined by an ELISA test. These findings could encourage further studies aimed at developing an effective biopesticide against SMV.
Achyrocline satureioides (Asteraceae) is a medicinal plant traditionally used in Argentina for the treatment of intestinal infections and various digestive disorders. Its infusion is widely utilised ...for respiratory problems and viral infections. The objective of this study was to investigate cytotoxicity, virucidal and antiviral properties of the cold aqueous extract (CAE) and hot aqueous extract (HAE) of this plant against Western equine encephalitis virus (WEEV). Cytotoxicity in Vero cells was evaluated by maximum non-cytotoxic concentration (MNCC), neutral red (NR) uptake and MTT reduction methods. To study the antiviral activity of aqueous extracts, plaque reduction assay was performed after pre-treatment of host cells, adsorption, penetration and post-penetration of the virus. Extracellular virus inactivation was also analysed by the same method. Extracts showed strong inhibitory activity after virus penetration with selective index values of 32 (NR) and 63.3 (MTT) for the CAE, and 16.2 (NR) and 24.3 (MTT) for the HAE. Both extracts exhibited virucidal action with lower efficacy than their antiviral properties. The present results demonstrate that aqueous extracts of A. satureioides are active against WEEV. Further studies are needed in order to identify which compounds could be responsible for this effect, and how they exert antiviral action.
The methanolic extract of Verbascum thapsus was evaluated for its antiviral activity against the pseudorabies virus strain RC/79 (PrV), and also for its cytotoxic activity on Vero cells. The extract ...showed CC
50
values of 1100 µg mL
−1
and 1426 µg mL
−1
by NRU and MTT assays, respectively. The 50% inhibitory concentration of the extract for PrV plaque formation was determined at 35 µg mL
−1
, and selectivity indices were 31.4 (NRU) and 40.7 (MTT). When cells were pre-treated with the extract prior to virus infection, the inhibition in plaque formation was 70%. PrV was highly inhibited when it was incubated with plant extract or when the extract was added during the adsorption phase (99%). However, no inhibitory effect was observed when the extract was added to the cells after the adsorption period. Thus, these results suggest that the methanolic extract of Verbascum thapsus may contain bioactive compound(s) that affect PrV mostly in the adsorption phase.
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Achyrocline satureioides (Lam.) DC. Asteraceae, ‘marcela del campo’, possess several pharmacological properties. Previously we reported antiviral activity of an aqueous extract of A. ...satureioides against an alphavirus, Western Equine Encephalitis virus. Alphaviruses are highly virulent pathogens which cause encephalitis in humans and equines. There are no effective antiviral to treat its infections. The aim of this study was to evaluate in vitro cytotoxic and antiviral activities against Western Equine Encephalitis virus of five water extract chromatographic fractions from A. satureioides and identify the main compounds of the bioactive fraction. Also, it was to assess in vivo cytogenotoxic ability of the active fraction. Cytotoxicity studies revealed low toxicity of the most of fractions in Vero and in equine peripheral blood mononuclear cells. Antiviral studies showed that the water crude extract – Sephadex LH 20 – fraction 3 MeOH–H2O (Fraction 3) was active against Western Equine Encephalitis virus with Effective Concentration 50%=5μg/ml. Selectivity Indices were 126.0 on Vero and 133.6 on peripheral blood mononuclear cells, four times higher than aqueous extract selectivity index. Regarding the mechanism of action we demonstrated that F3 exerted its action in intracellular replication stages. Further, fraction 3 showed important virucidal action. Fraction 3 contains, in order of highest to lowest: chlorogenic acid, luteolin, 5,7,8-trimethoxyflavone, 3-O-methylquercetin and caffeic acid. Fraction 3 did not induce in vivo toxic nor mutagenic effect. Therefore, it is safe its application as antiviral potential. Further studies of antiviral activity in vivo will be developed using a murine model.
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