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Nonstereoselective behavior of novel chiral organophosphorus pesticide Dufulin in cherry radish by different absorption methods
2022
Zheng, Ruonan | Shao, Siyao | Zhang, Subin | Yu, Zhiyang | Zhang, Weiwei | Wu, Tao | Zhou, Xin | Ye, Qingfu
Dufulin is a biologically derived antiviral agent chemically synthesized by α-phosphoramidate in sheep and is effective against viral diseases in plants such as tobacco, rice, cucumber and tomato. However, the environmental behaviors and fate of Dufulin under different cultivation systems remain unknown. This study investigates the absorption, translocation and accumulation of ¹⁴C-Dufulin stereoisomers introduced by pesticide leaf daubing and by mixing the pesticide with soil in different tissues of cherry radish. We particularly focused on whether the behaviors of Dufulin enantiomers in plants were stereoselective. In the leaf uptake experiments, S-Dufulin and R-Dufulin were transported both up and down, while more than 93% of the pesticide remained in the labeled leaves. During the radicular absorption experiments, both enantiomers of Dufulin were taken up by radish roots and moved to the upper part of the plant, while less than 0.2% Dufulin was absorbed from the soil. Hence, it was easier for Dufulin to enter plants through the leaf surface than through the roots. However, we found in this trial that the stereoisomers of Dufulin underwent nonstereoselective absorption and translocation, which implies that rac-Dufulin and its metabolites should be a major research priority. Overall, our results provide a relatively accurate prediction of the risk assessment of Dufulin, which will help guide its rational use in the environment as well as ensure eco-environmental safety and human health.
Mostrar más [+] Menos [-]Polystyrene microplastic particles in combination with pesticides and antiviral drugs: Toxicity and genotoxicity in Ceriodaphnia dubia
2022
Nugnes, Roberta | Russo, Chiara | Lavorgna, Margherita | Orlo, Elena | Kundi, M. (Michael) | Isidori, Marina
Freshwater ecosystems are recognized as non-negligible sources of plastic contamination for the marine environment that is the final acceptor of 53 thousand tons of plastic per year. In this context, microplastic particles are well known to directly pose a great threat to freshwater organisms, they also indirectly affect the aquatic ecosystem by adsorbing and acting as a vector for the transport of other pollutants (“Trojan horse effect”). Polystyrene is one of the most widely produced plastics on a global scale, and it is among the most abundant microplastic particles found in freshwaters. Nevertheless, to date few studies have focused on the eco-genotoxic effects on freshwater organisms caused by polystyrene microplastic particles (PS-MPs) in combination with other pollutants such as pharmaceuticals and pesticides. The aim of this study is to investigate chronic and sub-chronic effects of the microplastic polystyrene beads (PS-MP, 1.0 μm) both as individual xenobiotic and in combination (binary/ternary mixtures) with the acicloguanosine antiviral drug acyclovir (AC), and the neonicotinoid broad-spectrum insecticide imidacloprid (IMD) in one of the most sensitive non-target organisms of the freshwater food chain: the cladoceran crustacean Ceriodaphnia dubia. Considering that the individually selected xenobiotics have different modes of action and/or different biological sites, the Bliss independence was used as reference model for this research. Basically, when C. dubia neonates were exposed for 24 h to the mixtures during Comet assay, mostly an antagonistic genotoxic effect was observed. When neonates were exposed to the mixtures for 7 days, mostly an additive chronic toxic effect occurred at concentrations very close or even overlapping to the environmental ones ranging from units to tens of ng/L for PS-MPs, from tenths/hundredths to units of μg/L for AC and from units to hundreds of μg/L for IMD, revealing great environmental concern.
Mostrar más [+] Menos [-]Impact of long-term parental exposure to Tamiflu metabolites on the development medaka offspring (Oryzias latipes)
2020
Chen, Wei-Yu | Wu, Yen-Ting | Lin, Hsing-Chieh | Ieong, Meng-Ian | Lee, Bing-Heng
Despite the widespread use of the antiviral drug, Tamiflu®, little is known about the long-term toxic effects of drug or its metabolites in an aquatic ecosystem. This study integrated epidemiological and ecotoxicological methods to determine environmentally relevant concentrations of Tamiflu. A model based on the species medaka (Oryzias latipes) was then used to determine the health status and reproductivity of adults exposed to the drug as well as the embryonic development of offspring. The proposed ecotoxicological model was also used to quantitatively and qualitatively evaluate the toxicodynamic parameters related to egg production, hatchability, and development. Our results revealed that at an environmentally relevant exposure, Tamiflu and its metabolites had no adverse effects on growth, survival, or fecundity of adult medaka. Nonetheless, we observed a reduction in hatchability under exposure to 300 μg L⁻¹ and a reduction in body length under exposure exceeding 90 μg L⁻¹. Under exposure to 300 μg L⁻¹, the estimated spawning time to reach 50% of the maximum percentage of cumulative egg production (ET50) far exceeded that of the control group (without exposure to Tamiflu). We also observed a ∼ 3-fold decrease in maximum egg hatching (Eₘₐₓ). Based on an integrated epidemiological and ecotoxicological model, predictions of environmental concentrations of Tamiflu and its metabolites revealed that the influenza subtypes associated with increases in environmental concentrations: A(H3N2) > A(H1N1) > type B (in order of their effects). We also determined that A(H3N2) posed a potential risk to hatchability and development. Note however, the environmental concentrations of Tamiflu and its metabolites in most countries are lower than the effect concentrations derived in this study, indicating no hazards for aquatic environments. We recommend the use of hatchability and embryonic development as indicators in assessing the effects of long-term parental exposure to Tamiflu metabolites.
Mostrar más [+] Menos [-]Removal of the antiviral agent oseltamivir and its biological activity by oxidative processes
2012
Mestankova, Hana | Schirmer, Kristin | Escher, Beate I. | von Gunten, Urs | Canonica, Silvio
The antiviral agent oseltamivir acid (OA, the active metabolite of Tamiflu®) may occur at high concentrations in wastewater during pandemic influenza events. To eliminate OA and its antiviral activity from wastewater, ozonation and advanced oxidation processes were investigated. For circumneutral pH, kinetic measurements yielded second-order rate constants of 1.7 ± 0.1 × 10⁵ and 4.7 ± 0.2 × 10⁹ M⁻¹ s⁻¹ for the reaction of OA with ozone and hydroxyl radical, respectively. During the degradation of OA by both oxidants, the antiviral activity of the treated aqueous solutions was measured by inhibition of neuraminidase activity of two different viral strains. A transient, moderate (two-fold) increase in antiviral activity was observed in solutions treated up to a level of 50% OA transformation, while for higher degrees of transformation the activity corresponded to that caused exclusively by OA. OA was efficiently removed by ozonation in a wastewater treatment plant effluent, suggesting that ozonation can be applied to remove OA from wastewater.
Mostrar más [+] Menos [-]Degradation of Acyclovir by Zero-valent Iron Activated Persulfate Oxidation: Kinetics and Pathways Research
2022
Wei, Xingya | Li, Changjun | Gao, Naiyun
Acyclovir (ACV) is a commonly used antiviral drug; however, its poor bioavailability can lead to at least ng/L level residue in natural water. Sulfate radical, produced from persulfate (PS) by zero-valent iron (ZVI) activation, was demonstrated to effectively degrade ACV in this study. Influencing parameters, including ZVI dose, PS usage, initial ACV concentration, solution pH, and temperature, were evaluated to find the optimal degradation conditions. Intermediates were identified and main degradation pathways were proposed. Experiments showed that ACV degradation by ZVI/PS oxidation followed a pseudo zero-order reaction well (R² > 0.99). At pH ≦ 9, the optimal combination was 0.4 mM PS with 1.2 mM ZVI, in order to completely remove 10 μM ACV during 60-min reaction. Heat activation of PS would hinder the effect of ZVI if temperature was 45 °C or above. ACV could be oxidized to four major degradation products, including methoxyacetic acid (P1, C₃H₆O₃, m/z = 91), 1,1,2-trinitroethane (P2, C₂H₃N₃O₆, m/z = 165), trinitromethane (P3, CHN₃O₆, m/z = 151), and dinitromethane (P4, CH₂N₂O₄, m/z = 105). Though the mineralization rate was not high (about 24.0%), ZVI/PS oxidation was proved to be an available treatment method for ACV-induced water pollution.
Mostrar más [+] Menos [-]Ayurveda Rasayana as antivirals and immunomodulators: potential applications in COVID-19
2021
Coronavirus disease (COVID-19) has been declared as a pandemic by the World Health Organization with rapid spread across 216 countries. COVID-19 pandemic has left its imprints on various health systems globally and caused immense social and economic disruptions. The scientific community across the globe is in a quest for digging the effective treatment for COVID-19 and exploring potential leads from traditional systems of healthcare across the world too. Ayurveda (Indian traditional system of medicine) has a comprehensive aspect of immunity through Rasayana which is a rejuvenation therapy. Here we attempt to generate the potential leads based on the classical text from Ayurveda in general and Rasayana in particular to develop effective antiviral and/or immunomodulator for potential or adjunct therapy in SARS-CoV-2. The Rasayana acts not only by resisting body to restrain or withstand the strength, severity or progression of a disease but also by promoting power of the body to prevent the manifestation of a disease. These Rasayana herbs are common in practice as immunomodulator, antiviral and protectives. The studies on Rasayana can provide an insight into the future course of research for the plausible development of effective management of COVID-19 by the utilization and development of various traditional systems of healthcare. Keeping in view the current pandemic situation, there is an urgent need of developing potential medicines. This study proposes certain prominent medicinal plants which may be further studied for drug development process and also in clinical setup under repurposing of these herbs.
Mostrar más [+] Menos [-]Multi-core-shell composite SnO2NPs@ZIF-8: potential antiviral agent and effective photocatalyst for waste-water treatment
2019
Chandra, Ramesh | Singh, Vedita | Tomar, Shailly | Nath, Mala
With increasing environment pollution and bacterial transmitted viral diseases globally, the development of new, effective, and low-cost materials/strategies is the current major challenge. To combat with this alarming problem, three new multi-functional and thermally stable SnO₂NPs@ZIF-8 composites (NC1, NC2, and NC3) were synthesized by a facile and sustainable approach involving in situ encapsulation of SnO₂NPs (150, 300, and 500 μL suspension in methanol) within zeolitic imidazole framework at room temperature. The morphology and crystallinity of ZIF-8 remained unchanged upon the proper encapsulation of SnO₂NPs in its matrix. Herein, for the first time, the antiviral potential of ZIF-8 and SnO₂NPs@ZIF-8 against chikungunya virus is reported by investigating their cytotoxicity against Vero cell line (employing MTT ((3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide)) assay). The maximum non-toxic doses were 0.04 mg mL⁻¹ for ZIF-8 and SnO₂NPs@ZIF-8 and 0.1 mg mL⁻¹ for SnO₂NPs. Further, NC1 exhibited (based on plaque assay) reduction in viral load/titers up to > 80% during post-treatment and > 50% during pre-treatment, greater than that of ZIF-8 and SnO₂NPs due to synergistic effect. Further, NC1 (10 mg) exhibited enhanced photocatalytic efficiency (≥ 96%) for degradation of methylene blue (0.5 × 10⁻⁵ M) at pH ˃ 7.0. The probable mechanism for their antiviral activity and photocatalytic activity has been discussed. The multi-functional composites can effectively be used to reduce water pollution and as remedy for mosquito/bacterial transmitted viral diseases.
Mostrar más [+] Menos [-]Inactivation of influenza A virus via exposure to silver nanoparticle-decorated silica hybrid composites
2018
Park, SungJun | Ko, Young-Seon | Lee, Su-jin | Lee, Cheonghoon | Woo, Kyoungja | Ko, GwangPyo
Influenza A virus (IFV-A) is one of the main cause of seasonal flu and can infect various of host species via the reassortment of segmented RNA genomes. Silver nanoparticles (AgNPs) have been known as excellent antiviral agent against IFV. However, the use of free AgNPs has several major drawbacks, including the inherent aggregation among AgNPs and unwanted cytotoxic or genotoxic damages for human body via inhalation or ingestion. In this study, we assessed the efficacy of our novel ~ 30-nm-diameter AgNP-decorated silica hybrid composite (Ag30-SiO₂; ~ 400 nm in diameter) for IFV-A inactivation. Ag30-SiO₂ particles can inhibit IFV-A effectively in a clear dose-dependent manner. However, when real-time RT-PCR assay was used, merely 0.5-log₁₀ reduction of IFV-A was observed at both 5 and 20 °C. Moreover, even after 1 h of exposure to Ag30-SiO₂ particles, more than 80% of hemagglutinin (HA) damage and 20% of neuraminidase (NA) activities had occurred, and the infection of Madin-Darby Canine Kidney (MDCK) cells by IFV-A was reduced. The results suggested that the major antiviral mechanism of Ag30-SiO₂ particles is the interaction with viral components located at the membrane. Therefore, Ag30-SiO₂ particles can cause nonspecific damage to various IFV-A components and be used as an effective method for inactivating IFV-A.
Mostrar más [+] Menos [-]Performance and efficiency of removal of pharmaceutical compounds from hospital wastewater by lab-scale biological treatment system
2018
Azuma, Takashi | Otomo, Kana | Kunitou, Mari | Shimizu, Mai | Hosomaru, Kaori | Mikata, Shiori | Mino, Yoshiki | Hayashi, Tetsuya
The fate of pharmaceuticals after discharged from hospital into wastewater was clarified experimentally by using a new lab-scale conventional activated sludge (CAS) treatment reactor. The 43 target compounds belong to nine therapeutic classes (antivirals, antibacterials, anticancer drugs, psychotropics, antihypertensives, analgesic–antipyretics, contrast media, herbal medicines, and phytoestrogens) were selected with inclusion of 16 newly estimated compounds. The efficiency of the present reactor was estimated by comparing the reaction rate constant of the solid-water partition coefficients (log Kd) between liquid and solid samples and half-life during 48-h experiment obtained by using hospital effluents with those obtained by using STP wastewater. The results that no significant difference in removal efficiency was observed between both water samples (P > 0.05) indicate high reliability of the present lab-scale reactor. The actual rates of removal when hospital effluent was applied varied widely (mean, 59 ± 40%) independent of type of the pharmaceuticals. More than 90% of 17 compounds were removed after 8 h of treatment. However, the values for psychotropics (mean, 19 ± 26%) and contrast media (mean, 24 ± 17%) were generally low, indicating high stability. The log Kd values ranged from 1.3 to 4.8. Notably, clarithromycin, acridine, and glycitein could be removed in both liquid and solid phases. The dominant removal mechanisms were found to be different for individual pharmaceutical. These results suggest the effectiveness of introduction of the lab-scale biological treatment system for development of a new solution for discharge of pharmaceuticals from hospital.
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