The anti-staphylococcal fusidic acid as an efflux pump inhibitor combined with fluconazole against vaginal candidiasis in mouse model.

BACKGROUND: Candida albicans is the most common fungus that causes vaginal candidiasis in immunocompetent women and catastrophic infections in immunocompromised patients. The treatment of such infections is hindered due to the increasing emergence of resistance to azoles in C. albicans. New treatment approaches are needed to combat candidiasis especially in the dwindled supply of new effective and safe antifungals. The resistance to azoles is mainly attributed to export of azoles outside the cells by means of the efflux pump that confers cross resistance to all azoles including fluconazole (FLC). OBJECTIVES: This study aimed to investigate the possible efflux pump inhibiting activity of fusidic acid (FA) in C. albicans resistant isolates and the potential use of Fusidic acid in combination with fluconazole to potentiate the antifungal activity of fluconazole to restore its activity in the resistant C. albicans isolates. METHODS: The resistance of C. albicans isolates was assessed by determination of minimum inhibitory concentration. The effect of Fusidic acid at sub-inhibitory concentration on efflux activity was assayed by rhodamine 6G efflux assay and intracellular accumulation. Mice model studies were conducted to evaluate the anti-efflux activity of Fusidic acid and its synergistic effects in combination with fluconazole. Impact of Fusidic acid on ergosterol biosynthesis was quantified. The synergy of fluconazole when combined with Fusidic acid was investigated by determination of minimum inhibitory concentration. The cytotoxicity of Fusidic acid was tested against erythrocytes. The effect of Fusidic acid on efflux pumps was tested at the molecular level by real-time PCR and in silico study. In vivo vulvovaginitis mice model was used to confirm the activity of the combination in treating vulvovaginal candidiasis. RESULTS: Fusidic acid showed efflux inhibiting activity as it increased the accumulation of rhodamine 6G, a substrate for ABC-efflux transporter, and decreased its efflux in C. albicans cells. The antifungal activity of fluconazole was synergized when combined with Fusidic acid. Fusidic acid exerted only minimal cytotoxicity on human erythrocytes indicating its safety. The FA efflux inhibitory activity could be owed to its ability to interfere with efflux protein transporters as revealed by docking studies and downregulation of the efflux-encoding genes of both ABC transporters and MFS superfamily. Moreover, in vivo mice model showed that using fluconazole-fusidic acid combination by vaginal route enhanced fluconazole antifungal activity as shown by lowered fungal burden and a negligible histopathological change in vaginal tissue. CONCLUSION: The current findings highlight FA's potential as a potential adjuvant to FLC in the treatment of vulvovaginal candidiasis.

Doping zinc oxide and titanium dioxide nanoparticles with gold induces additional oxidative stress, membrane damage, and neurotoxicity in Mytilus galloprovincialis: Results from a laboratory bioassay.

BACKGROUND: While previous studies have provided insights into the effects of zinc oxide (ZnO) and titanium dioxide (TiO2) nanoparticles (NPs) on aquatic organisms, there is still a substantial amount of information lacking about the possible effects of their doped counterparts. The goal of the current work was to address this gap by examining Mytilus galloprovincialis reaction to exposure to doped and undoped nanoparticles. METHODS: Two concentrations (50 or 100 µg/L) of undoped ZnO and TiO2 NPs, as well as their gold (Au) doped counterparts, were applied on mussels for 14 days, and the effects on biomarkers activities in digestive glands and gills were assessed by spectrophotometry. RESULTS: The NPs were quasi-spherical in shape (below 100 nm), stable in seawater, and with no aggregation for both doped and undoped forms. Analytical results using inductively coupled plasma atomic emission spectroscopy indicated the uptake of NPs in mussels. Furthermore, it was found that biometal dyshomeostasis could occur following NP treatment and that doping the NPs aggravated this response. At the biochemical level, exposure to undoped NPs caused membrane damage, neurotoxic effect, and changes in the activities in the gills and digestive glands of superoxide dismutase, catalase, and glutathione-S-transferase, in a concentration and organ-dependent manner. CONCLUSION: Doping ZnO NPs and TiO2NPs with Au induced additional oxidative stress, membrane damage, and neurotoxicity in mussels.

HPLC-DAD-MS Characterization, Antioxidant Activity, α-amylase Inhibition, Molecular Docking, and ADMET of Flavonoids from Fenugreek Seeds.

Fenugreek (Trigonella foenum-graecum) has a great beneficial health effect; it has been used in traditional medicine by many cultures. Likewise, the α-amylase inhibitors are potential compounds in the development of drugs for the treatment of diabetes. The beneficial health effects of fenugreek lead us to explore the chemical composition of the seeds and their antioxidant and α-amylase inhibition activities. The flavonoid extraction from fenugreek seeds was achieved with methanol through a Soxhlet apparatus. Then, the flavonoid glycosides were characterized using HPLC-DAD-ESI-MS analysis. The antioxidant capacity of fenugreek seed was measured using DPPH, FRAP, ABTS, and CUPRAC assays. Finally, the α-amylase inhibition activity was carried out using in vitro and in silico methods. The methanolic extract was found to contain high amounts of total phenolics (154.68 ± 1.50 µg GAE/mg E), flavonoids (37.69 ± 0.73 µg QE/mg E). The highest radical-scavenging ability was recorded for the methanolic extract against DPPH (IC50 = 556.6 ± 9.87 µg/mL), ABTS (IC50 = 593.62 ± 9.35 µg/mL). The ME had the best reducing power according to the CUPRAC (A 0.5 = 451.90 ± 9.07 µg/mL). The results indicate that the methanolic extracts of fenugreek seed best α-amylase inhibition activities IC50 = 653.52 ± 3.24 µg/mL. Twenty-seven flavonoids were detected, and all studied flavonoids selected have good affinity and stabilize very well in the pocket of α-amylase. The interactions between the studied flavonoids with α-amylase were investigated. The flavonoids from fenugreek seed present a good inhibitory effect against α-amylase, which is beneficial for the prevention of diabetes and its complications.

In Vitro Antibacterial, Antioxidant, Anticholinesterase, and Antidiabetic Activities and Chemical Composition of Salvia balansae.

CONTEXT: Salvia balansae de Noé (S. balansae) (Lamiaceae) is known to be an important plant used in folk medicine as an herbal remedy in Algeria. OBJECTIVE: The purpose of the present study was to demonstrate the phytochemical composition, antioxidant activities, enzyme inhibitory activities, and antimicrobial activities of S. balansae extracts. MATERIALS AND METHODS: A methanolic extract and a petroleum ether extract from the aerial parts of the plant were assessed for their chemical composition. HPLC-MS and HPLC-DAD assessed the content of phenols, GC-MS the fatty acid composition, and ICP-MS the mineral profiles of the plant. Additionally, we evaluated the bioactivities of S. balansae extracts by the DPPH, ABTS, and CUPRAC assays, including the antioxidant potential against AChE, BChE, α-amylase, and α-glucosidase for enzyme inhibition. The antibacterial and antifungal activities of the methanolic extract were determined by the disc diffusion test against several strains of bacteria and yeasts. RESULTS: Our findings revealed that the aerial parts of S. balansae were rich in phytochemical components and contained large amounts of minerals. Quantitative analysis of phenolic compounds by HPLC-DAD revealed the presence of 12 compounds in three major classes, flavonoids, hydroxycinnamic acid, and phenolic acid derivatives, with 0.61, 0.45, and 0.29 mg/g of extract, respectively. Nine phenolic constituents were quantified by HPLC-MS analysis; catechin (72.5%) was the main compound, followed by myricetin (21.7%). The fatty acid composition of the S. balansae petroleum ether extract by GC-MS analysis was quantified. Seventeen compounds, including palmitic acid, were identified as the major fatty acids. The antioxidant activity of the S. balansae extracts was measured by three different methods: the methanol extract provided better results than the petroleum ether extract, and interesting values were noted for the DPPH, ABTS, and CUPRAC assays of 242.7 ± 7.44, 124.1 ± 9.70, and 222.9 ± 6.05 µg/mL, respectively. The enzyme inhibition activity of the plant could not be determined. The antimicrobial results of the methanolic extract obtained from the disc diffusion method, followed by measurements of MIC, MBC, and MFC against several bacteria and yeasts, indicated that S. balansae exhibited noticeable antimicrobial and antifungal activities. CONCLUSIONS: These results provided new data about the main phenolic compounds and biological activities of extracts of the aerial parts of S. balansae, which might be an alternative source for synthetic bioactive compounds.

Statistical Design and Optimization of Cr (VI) Adsorption onto Native and HNO3/NaOH Activated Cedar Sawdust Using AAS and a Response Surface Methodology (RSM).

The removal of heavy metals from wastewater has become the subject of considerable interest at present. Thus, the use of novel adsorbents that are highly efficient is of critical importance for the removal of Cr (VI) ions from aqueous media. The adsorption of Cr (VI) ions from aqueous solutions by a new adsorbent, cedar wood sawdust, and the optimization of its adsorption parameters, were investigated in this study. Cedar wood sawdust was used in its native and HNO3/NaOH chemically modified forms as new low-cost sorbents to remove Cr (VI) ions from aqueous solutions in a batch system. The adsorption conditions were analyzed via response surface methodology. The RSM results showed that the optimal adsorption conditions yielding the best response were an adsorbent mass of 2 g for native Cedar and 1.125 g for its activated form, a metal concentration of 150 mg/L for native Cedar and 250 mg/L for activated, a temperature of 50 °C, a pH of 1, and a contact time of 67.5 min. At optimum adsorption conditions, the maximum adsorption capacities and the adsorption yields were 23.64 mg/g and 84% for native Cedar and 48.31 mg/g and 99% for activated Cedar, respectively.

Relocating Glyceryl Trinitrate as an Anti-Virulence Agent against Pseudomonas aeruginosa and Serratia marcescens: Insights from Molecular and In Vivo Investigations.

The problem of antibiotic resistance is a global critical public health concern. In light of the threat of returning to the pre-antibiotic era, new alternative approaches are required such as quorum-sensing (QS) disruption and virulence inhibition, both of which apply no discernible selective pressure on bacteria, therefore mitigating the potential for the development of resistant strains. Bearing in mind the significant role of QS in orchestrating bacterial virulence, disrupting QS becomes essential for effectively diminishing bacterial virulence. This study aimed to assess the potential use of sub-inhibitory concentration (0.25 mg/mL) of glyceryl trinitrate (GTN) to inhibit virulence in Serratia marcescens and Pseudomonas aeruginosa. GTN could decrease the expression of virulence genes in both tested bacteria in a significant manner. Histopathological study revealed the ability of GTN to alleviate the congestion in hepatic and renal tissues of infected mice and to reduce bacterial and leukocyte infiltration. This study recommends the use of topical GTN to treat topical infection caused by P. aeruginosa and S. marcescens in combination with antibiotics.

The multifaceted effects of fluoranthene and polystyrene on the taxonomic composition and associated functional traits of marine meiofauna, by using single and mixture applications.

The current experiment measured the multifaceted effects of polystyrene and fluoranthene, acting alone or in a mixture on marine meiofauna, but with a special focus on nematodes' morphological and functional traits. The results showed changes in the abundances for all tested concentrations of both compounds. The nematode communities exposed to the highest concentrations of fluoranthene (30 ng.g-1 Dry Weight (DW)) and polystyrene (100 mg.kg-1 DW) alone or in a mixture, were significantly less diverse compared to control and were associated with significant changes in the percentage of taxonomic composition and feeding-guilds. The most sensitive taxa to fluoranthene comprised epistratum feeders, whereas the nematodes mostly affected by polystyrene were omnivores-carnivores. A new functional tool, the Index of Sensitivity (IOS), proved to be reliable in depicting the changes that occurred in the taxonomic and functional features of the nematofauna.

Are iron ore microparticles toxic for the European clam Ruditapes decussatus? Response elements from biomarker activities and in silico modeling.

Inevitably, high concentrations of iron, the most widely produced ore globally, can be found in aquatic environments. To assess the toxicity of iron on aquatic organisms, Ruditapes decussatus specimens were subjected to microparticles derived from two types of iron ore (hematite and magnetite) at four different concentrations (0.5, 1, 1.5, and 5 g/L). The findings revealed that both types of iron ore were absorbed by clams in a concentration-dependent manner. Biomarkers analysis demonstrated significant and organ-specific impacts on the health of the clams caused by these microparticles, which was further supported by computational analyses on bioavailability. Within seven days of exposure, changes were observed in the activities of several enzymes, including catalase, acetylcholinesterase, and glutathione S-transferases, as well as in the rate of lipid peroxidation in both the digestive gland and gills. This study provides an environmental perspective on the toxicological effects of iron ore microparticles.

Dual biocontrol potential of the entomopathogenic fungus Akanthomyces muscarius against Thaumetopoea pityocampa and plant pathogenic fungi.

Akanthomyces spp. species are known for their capacity to biocontrol of certain insects and plant pathogens; however, their ability to biocontrol the pine processionary (Thaumetopoea pityocampa) and certain phytopathogenic fungi belonging to the genera Fusarium and Curvularia have not been studied before. In this study, a strain from Akanthomyces muscarius was isolated from wheat grains and then identified by morphological and molecular tests. The strain was further studied for its capacity to control Thaumetopoea pityocampa larvae through dose-mortality tests, and its ability to control some phytopathogenic fungi strains of the genera Fusarium and Curvularia was studied through direct confrontation tests. Dose-mortality tests at three concentrations of Akanthomyces muscarius against the first instar larvae revealed a mortality of 92.15% after 11 days for the concentration of 2.3 × 106conidia.ml-1, with a median lethal concentration of 7.6 x103 conidia.ml1. Our isolate also showed antifungal activity against these phytopathogenic fungi with inhibition rates ranging from 39.61% to 52.94%. Akanthomyces muscarius proved to be a promising biocontrol agent for plant pests and diseases.

Exploration and Evaluation of Secondary Metabolites from Trichoderma harzianum: GC-MS Analysis, Phytochemical Profiling, Antifungal and Antioxidant Activity Assessment.

In this study, we investigated in vitro the potential of Trichoderma harzianum to produce bioactive secondary metabolites that can be used as alternatives to synthetic compounds. The study focused on analyzing two extracts of T. harzianum using ethyl acetate and n-butanol solvents with different polarities. The extracts were examined using phytochemical analysis to determine the content of polyphenols, flavonoids, tannins, and alkaloids. Thin-layer chromatography (TLC) and Gas chromatography-mass spectroscopy (GC-MS) analysis were used to profile volatile organic metabolites (VOCs) present in the extracts. Furthermore, the extracts were tested for their antifungal ability using the poison food technique. For measuring antioxidant activity, the 1,1-diphenyl-2-picryl-hydrazyl (DPPH) test was used. Trichoderma harzianum was shown to have a significantly high content of tannins and alkaloids, with a noticeable difference between the two extracts. GC-MS analysis identified 33 potential compounds with numerous benefits that could be used in agriculture and the medicinal industry. Moreover, strong antifungal activity was identified against Sclerotinia sclerotiorum by 94.44%, Alternaria sp. by 77.04%, and Fusarium solani by 51.48; similarly, the IC50 of antioxidant activity was estimated for ethyl acetate extract by 71.47% and n-butanol extract by 56.01%. This leads to the conclusion that Trichoderma harzianum VOCs play a significant role as an antifungal and antioxidant agent when taking into account the advantageous bioactive chemicals noted in the extracts. However, to our knowledge, this is the first study in Algeria presenting detailed phytochemical analysis and GC-MS profiling of Trichoderma harzianum for two extracts, ethyl acetate and n-butanol.

The development of decontamination methods in coastal marine habitats by transplantation of the mussel Mytilus galloprovincialis (Lamarck, 1819): Comparison between in vivo and in situ investigations.

The health status of Mytilus galloprovincialis native from a polluted habitat was surveyed before and after 30 and 60 days of in situ transplantation and in vivo experiments. The results showed a reduction in filtration rate by 24 % and 45 %, respectively, after 60 days of in vivo and in situ experiments compared to the rates at polluted sites. The respiration rate reached a minimum of 0.081 ± 0.05 mg O2.L-1 after 60 days of in situ transplantation. Moreover, the antioxidant activities were changed in a time-dependent manner for both transplantation conditions. The highest superoxide dismutase and catalase activities corresponded to the stressed mussels and declined by 76 % and 54 %, respectively, after 60 days of in situ transplantation. Changes in lipid peroxidation and acetylcholinesterase activity were observed in internal organs following 60 days of transplantation. At this time slot, the lowest content of metals and microplastics was also noticed.

Possible Interaction between ZnS Nanoparticles and Phosphonates on Mediterranean Clams Ruditapes decussatus.

This study aims to evaluate the toxicity of ZnS nanoparticles (ZnS NP50 = 50 µg/L and ZnS NP100 = 100 µg/L) and diethyl (3-cyano-1-hydroxy-2-methyl-1-phenylpropyl)phosphonate or P (P50 = 50 µg/L and P100 = 100 µg/L) in the clams Ruditapes decussatus using chemical and biochemical approaches. The results demonstrated that clams accumulate ZnS NPs and other metallic elements following exposure. Moreover, ZnS NPs and P separately lead to ROS overproduction, while a mixture of both contaminants has no effect. In addition, data showed that exposure to P100 resulted in increased levels of oxidative stress enzyme activities catalase (CAT) in the gills and digestive glands. A similar trend was also observed in the digestive glands of clams treated with ZnS100. In contrast, CAT activity was decreased in the gills at the same concentration. Exposure to ZnS100 and P100 separately leads to a decrease in acetylcholinesterase (AChE) levels in both gills and digestive glands. Thus, AChE and CAT after co-exposure to an environmental mixture of nanoparticles (ZnS100) and phosphonate (P100) did not show any differences between treated and non-treated clams. The outcome of this work certifies the use of biomarkers and chemical assay when estimating the effects of phosphonate and nanoparticles as part of an ecotoxicological assessment program. An exceptional focus was given to the interaction between ZnS NPs and P. The antioxidant activity of P has been demonstrated to have an additive effect on metal accumulation and antagonistic agents against oxidative stress in clams treated with ZnS NPs.

Phytochemicals, Antioxidant and Antimicrobial Potentials and LC-MS Analysis of Centaurea parviflora Desf. Extracts.

Centaurea parviflora (C. parviflora), belonging to the family Asteraceae, is an Algerian medicinal plant used in folk medicine to treat different diseases related to hyperglycemic and inflammatory disorders, as well as in food. The present study aimed to assess the total phenolic content, in vitro antioxidant and antimicrobial activity and phytochemical profile of the extracts of C. parviflora. The extraction of phenolic compounds from aerial parts was conducted using solvents of increasing polarity starting from methanol, resulting in crude extract (CE), to chloroform extract (CHE), ethyl acetate extract (EAE) and butanol extract (BUE). The total phenolic, flavonoid and flavonol contents of the extracts were determined using the Folin-Ciocalteu and AlCl3 methods, respectively. The antioxidant activity was measured with seven methods: 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, galvinoxyl free-radical-scavenging test, 2,2'-Azino-Bis(3-Ethylbenzothiazoline-6-Sulfonic Acid) (ABTS) assay, cupric reducing antioxidant capacity (CUPRAC), reducing power, Fe+2-phenanthroline reduction assay and superoxide-scavenging test. The disc-diffusion method aimed at testing the sensitivity of bacterial strains toward our extracts. A qualitative analysis with thin-layer chromatography of the methanolic extract was performed. Moreover, HPLC-DAD-MS was used to establish the phytochemical profile of the BUE. The BUE was found to contain high amounts of total phenolics (175.27 ± 2.79 µg GAE/mg E), flavonoids (59.89 ± 0.91 µg QE/mg E) and flavonols (47.30 ± 0.51 µg RE/mg E). Using TLC, different components such as flavonoids and polyphenols were noted. The highest radical-scavenging ability was recorded for the BUE against DPPH (IC50 = 59.38 ± 0.72 µg/mL), galvinoxyl (IC50 = 36.25 ± 0.42 µg/mL), ABTS (IC50 = 49.52 ± 1.54 µg/mL) and superoxide (IC50 = 13.61 ± 0.38 µg/mL). The BUE had the best reducing power according to the CUPRAC (A0.5 = 71.80 ± 1.22 µg/mL), phenanthroline test (A0.5 = 20.29 ± 1.16 µg/mL) and FRAP (A0.5 = 119.17 ± 0.29 µg/mL). The LC-MS analysis of BUE allowed us to identify eight compounds including six phenolic acids and two flavonoids: quinic acid, five chlorogenic acid derivatives, rutin and quercetin 3-o-glucoside. This preliminary investigation revealed that the extracts of C. parviflora have a good biopharmaceutical activity. The BUE possesses an interesting potential for pharmaceutical/nutraceutical applications.

Successive Solvent Extraction, Characterization and Antioxidant Activities of Cardoon Waste (Leaves and Stems) Extracts: Comparative Study.

The main interest in the valorization of vegetable wastes is due to the peculiarity of their chemical composition in substances that present important properties. Among these substances, antioxidants could replace those industrially manufactured. In the present study, three solvents of different polarities (hexane, ethanol, and water) were applied for the extraction of phenolic compounds from Cynara cardunculus L. waste using two extraction methods: Soxhlet Extraction (SE) and Ultrasonic-Assisted Extraction (UAE). The obtained extracts were then characterized by Fourier-Transform Infrared (FTIR) spectroscopy and spectrophotometric determination of Total Phenolics (TPC), Total Flavonoids (TFC), and Condensed Tannins (CT). Total Antioxidant Capacity (TAC) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity of ethanol and water extracts of leaves and stems were also evaluated. High extraction yields were obtained by UAE. Water extracts had high yield regardless of the technique used for leaves and stems, and these extracts showed high TAC of 534.72 ± 3.83 mg AAE/g FM for leaves and 215.70 ± 8.87 mg AAE/g FM (mg of ascorbic acid equivalent per g of FM) for stems, and IC50 of 2077.491 µg/mL for leaves and 1248.185 µg/mL for stems. We explain the latter by the high total phenolic contents (TPCs), which reach 579.375 ± 3.662 mg GAE/g FM (mg of gallic acid equivalents per g of fresh matter) for leaves and 264.906 ± 3.500 mg GAE/g FM for stems. These results confirmed that the leaves and stems of the studied cardoon waste were, indeed, interesting sources of natural antioxidants.

Physiological Impairment and Biochemical Modifications Induced by Triclosan in Mediterranean Mussels.

The effects of pharmaceutical under aquatic biota are still not well established. In this investigation, we assessed the results of a common pharmaceutical's, triclosan (TCS), treatment on physiological and biochemical status of the Mediterranean mussels. Filtration and respiration rates were statistically reduced after treatment with highest considered concentration TCS2 = 100 µg·L-1. However, no modification (p > 0.05) was detected after treatment with TCS1 = 50 µg·L-1. For biochemical responses, oxidative stress parameters including H2O2 level and antioxidant enzymes were enhanced following concentration in considered organs. In parallel, Malondialdheyde content was measured in mussels after TCS treatment and lipid peroxidation occurred at high TCS concentration. Neurotoxicity evaluated by acetylcholinesterase (AChE) activity was induced in gills and digestive glands after exposure to TCS2. Overall, physiological impairment, oxidative stress, lipid peroxidation and neurotoxicity could be induced by triclosan in mussels. The association of physiological and biochemical biomarkers constitute a useful tool to measure the impact of pharmaceuticals in marine organism.

Effects of an Endocrine Disruptor Triclosan on Ruditapes decussatus: Multimarker and Histological Approaches.

The aim of this work was to study the ecotoxicological effects of an endocrine disruptor triclosan on the clam Ruditapes decussatus. The bivalves were exposed to three concentrations of this biocide (C1 = 100 ng/L, C2 = 200 ng/L and C3 = 500 ng/L) for three and seven days. The impact was assessed at the gills and digestive glands, through activities of an antioxidant defense biomarker (Gluthatione S-Transferase, GST), a damage biomarker (Malondialdehyde, MDA), and a neurotoxicity biomarker (Acetylcholinesterase, AChE). Furthermore, histological traits were approached in different organs to evaluate any possible alteration induced by triclosan. It appears from this study that both gills and digestive glands responded discernibly to triclosan and effects were concentration-dependent. The stressed clams showed a significant increase in their GST and MDA activities in gills and digestive glands compared to controls for both time slots considered. In turn, the AChE activity was clearly inhibited in both organs in a time dependent way. The histological study made it possible to observe several structural pathologies caused by triclosan in the gills and the digestive gland. These alterations consisted mainly of inflammatory reactions, malformations of the lamellae and fusion of the gill filaments, degeneration of the connective tissue, and the erosion of the gill cilia with the appearance of certain severe alterations (cell necrosis and apoptosis), which can thus cause a malfunction of the gills and eventually lead to a reduction in oxygen consumption and a disruption of the osmoregulation for bivalves. Alterations in the digestive gland have also been detected, mainly by epithelial alterations, thinning of the tubules, and alteration of the basal cell membrane which can impair the ability of clams to absorb food. At germinal cells, several damages were observed in the oocytes which probably disturbed the reproductive function and the fertility of the clams. The damages observed in female gonads were caused by the cytolysis of a large number of oocytes through autophagy and necrosis at 200 ng triclosan/L. Moreover, at 500 ng triclosan/L, hemocytic infiltration was observed in acini and apoptotic bodies reflected in the fragmentation of more than 90% of oocytes.

How toxic is the COVID-19 drug azithromycin in the presence of Posidonia oceanica? Toxicokinetics and experimental approach of meiobenthic nematodes from a metallically pristine area.

The current study presents the results of an experiment carried to assess the impact of azithromycin, a COVID-19 drug, probably accumulated in marine sediments for three years, since the start of the pandemic, on benthic marine nematodes. It was explored the extent to which a common macrophyte from the Mediterranean Sea influenced the toxic impact of azithromycin on meiobenthic nematodes. Metals are known to influence toxicity of azithromycin. The nematofauna from a metallically pristine site situated in Bizerte bay, Tunisia, was exposed to two concentrations of azithromycin [i.e. 5 and 10 µg l-1]. In addition, two masses of the common macrophyte Posidonia oceanica [10 and 20% Dry Weight (DW)] were considered and associated with azithromycin into four possible combinations. The abundance and the taxonomic diversity of the nematode communities decreased significantly following the exposure to azithromycin, which was confirmed by the toxicokinetic data and behaving as substrate for P-glycoprotein (P-gp). The toxicity of 5 µg l-1 dosage of azithromycin was partially reduced at 10% DW of Posidonia and completely at 20% DW. The results showed that 5 µg l-1 of azithromycin can be reduced by the macrophyte P. oceanica when present in the environment at low masses as 10% DW.

Metallic nanoparticles affect uptake of polycyclic aromatic hydrocarbons and impacts in the Mediterranean mussels Mytilus galloprovincialis.

The impact of metallic nanoparticles (NPs) on the uptake and toxicity of persistent organic pollutants by marine bivalves was assessed through a comparative laboratory study by exposing mussels to polycyclic aromatic hydrocarbon (PAHs), in the presence and absence of ZnO and TiO2 NPs. PAHs and NPs concentration was analyzed after 14 days of exposure in mussels by GC/MS and ICP/AES. Furthermore, impact on the physiology and neurotoxicity of PAHs and NPs acting alone or in mixtures were also determined. Our results confirmed the bio-uptake of PAHs and NPs by mussels. In addition, the exposure NPs-PAHs resulted in different bio-uptake profile to that of PAHs alone. The NPs and accumulation of PAHs led to disturbance of essential metals concentration and to different impact profiles in the filtration and respiration capacities as well as in the acetylcholinesterase activity. Antagonist interactions between NPs and PAHs could occur after exposure.

Ecotoxicity of chrysene and phenanthrene on meiobenthic nematodes with a case study of Terschellingia longicaudata: Taxonomics, toxicokinetics, and molecular interactions modelling.

Polycyclic aromatic hydrocarbons (PAHs) are toxic for humans and marine fauna alike. The current study assessed the impact of PAHs on the migratory behaviour of meiobenthic nematodes collected from the Bizerte lagoon, Tunisia. The experiment lasted for 15 days and was carried in open microcosms, which comprised a lower, contaminated and an upper, uncontaminated compartment. Three treatments were used, for each of them an untreated control was set up: sediment contaminated with chrysene (116 ng g-1 dry weight (DW), with phenanthrene (116 ng g-1 DW) and a mixture of both. The results showed a significant decrease in diversty and abundance in the lower, contaminated compartments compared to the upper zones. The results also highlighted that under an increased stress some species progressively increased in number, these were considered PAH-tolerant species such as Odontophora villoti, some others had an occasionally increased in number were considered as opportunistic species, such as Paracomesoma dubium and the species that showed a progressive decreased in number, such as Metoncholaimus pristiurus and Steineria sp., Terschellingia. longicaudata, and Oncholaimellus sp. were classified as PAH-sensitive. Moreover, an increase in the activity of biochemical biomarkers was observed following the exposure of males and gravid females of T. longicaudata to 29, 58 and 87 ng g-1 DW of chrysene and phenanthrene paralleled by a higher vulnerability of the latter demographic category. Besides, a significant decrease in fertility of females and an increase in pharyngeal sucking power were observed for both types of PAHs considered. The sex ratio was also significantly imbalanced in the favor of males, which suggest that chrysene and phenanthrene affect also the hormone system of T. longicaudata. The high affinities of these PAHs and their molecular interactions with both germ line development protein 3 (GLD-3) and sex-determining protein (SDP) may justify these results and explain the toxicokinetic attributes.

Zn application through seed priming improves productivity and grain nutritional quality of silage corn.

The micronutrient application in agriculture takes place through soil application, foliar spraying or added as seed treatments. The latter method, the nutri-priming, is an appealing option due to the easiness in handling it, environment-friendly, cost effectiveness and efficient against multiple environmental stressors. To assess the feasibility of Zn-priming technique on seeds germination, two experiments were conducted and assessed the efficiency on the growth rate, yield and biofortification on the forage maize (Zea mays L.). The first laboratory experiment assessed the effect of Zn-priming for three-time exposures (i.e., 8, 16 and 24 h) on germination parameters. The second experiment was done in a greenhouse, by using the 10 seeds obtained from 24 h priming. Five seed pretreatments were studied (0, 0.1, 0.5, 1 and 11 2 % of zinc sulfate heptahydrate (ZnSO4·7H2O)) compared to the recommended dose (5 ppm of Zn at 5-9 leaf stage) provided by soil application. The obtained results revealed that all seed priming, including hydro-priming, improve seed germination performance. Zn-priming increased the grain yield and helped to enrich the seeds in this element, especially seedlings treated with 0.5 % Zn sulphate for 24 h leading to an increase in yield by 47 % and in Zn content by 15 %. The comparison of the results from both techniques showed that Zn-priming could be was very effective than the traditional direct application in soil.