Multiple Toxic Effects Research Articles

Oxidative stress, intestinal damage, and cell apoptosis: Toxicity induced by fluopyram in Caenorhabditis elegans

Fluopyram, a succinate dehydrogenase inhibitor fungicide and nematicide, has been used extensively for agricultural pest control and toxicologically affects non-target organisms. In the present study, Caenorhabditis elegans, a well-established model organism, was used to evaluate the toxic effect of fluopyram and the possible molecular mechanisms. C. elegans was exposed to fluopyram for 24 h at three sublethal concentrations (0.01, 0.05 and 0.25 mg/L) and the physiological, biochemical, and molecular indicators were examined. The results showed that sublethal exposure to fluopyram could cause damage to growth, locomotion behavior, feeding, lifespan and reproduction of the nematodes. Fluopyram exposure induced oxidative stress as indicated by increase of ROS production, lipofuscin and lipid accumulation, and MDA level in the nematodes. In contrast, exposure to fluopyram significantly decreased the activities of target enzyme SDH and antioxidant enzymes including SOD, CAT and GST. Moreover, the expression of genes associated with oxidative stress (e.g., gst-4, sod-3, fat-7, mev-1 and daf-16), intestinal damage (e.g., mtm-6, nhx-2, opt-2, pkc-3, par-6, act-5 and egl-8), and cell apoptosis (e.g., ced-13, ced-3, egl-38, efl-2, cep-1 and lgg-1) was significantly influenced after exposure to fluopyram. According to Pearson correlation analyses, significant correlation existed between 190 pairs of parameters, which indicated that fluopyram induced multiple toxic related effects in C. elegans. These findings suggest that oxidative stress, intestinal damage, and cell apoptosis may play major roles in toxicity of fluopyram in the nematodes.

Concentration-dependent transcriptome of zebrafish larvae for environmental bisphenol S assessment

The widespread use of bisphenol S (BPS) as an alternative to bisphenol A has captured attention due to its potential toxicity to aquatic organisms. In the present study, the zebrafish was used as a model to evaluate the toxicity of BPS and determine the underlying mechanisms. The environmental concentration-dependent (0, 0.1, 1, 10, 100, and 1000 μg/L BPS) transcriptome approach was employed in combination with toxicity assays to address the problem. Based on a weighted correlation network analysis, we speculated that excess reactive oxygen species (ROS) may initiate cellular events in BPS-exposed zebrafish, leading to multiple toxic effects. Furthermore, we used pathway enrichment analysis to identify key pathways (MAPK signalling pathway and metabolic pathways) that link the molecular mechanisms with different toxic effects. In addition, we performed protein-protein network and shortest path analyses to identify six hub genes (erbb2, rrm2, rps27a, his2h3c, cdk1, and mcm5) and their interactions. Moreover, we suggest that BPS may interact with erbb2 by molecular docking. Thus, the BPS-erbb2 interaction may activate the MAPK signalling and metabolic pathways, resulting in ROS production and then caused multiple toxic effects in zebrafish. This study provides information for characterising the mechanisms of BPS exposure in aquatic environments.

Lactic acid bacteria alleviate liver damage caused by perfluorooctanoic acid exposure via antioxidant capacity, biosorption capacity and gut microbiota regulation

Perfluorooctanoic acid (PFOA) is an environmental pollutant that has multiple toxic effects. Although some medicines and functional food ingredients are currently being used to alleviate the biological toxicity effects caused by PFOA, these candidates all show potential side effects and cannot prevent the accumulation of PFOA in the body, making them unable to be used as a daily dietary supplement to relieve the toxic effects of PFOA. However, new research has shown that lactic acid bacteria (LAB) can alleviate toxicity caused by exposure to foreign substances. In this study, multiple strains of LAB with different adsorption capacities or antioxidant capacities were used to analyse their mitigation effects of on liver damage caused by PFOA exposure. The results showed that the adsorption capacity and antioxidant capacity of LAB could alleviate the liver toxicity of PFOA to a certain extent. Moreover, treatment with some strains of LAB was able to recover the gut microbiota dysbiosis caused by PFOA exposure, such as by increasing the relative abundances of Patescibacteria, Proteobacteria, Akkermansia and Alistipes or decreasing the abundances of Bacteroides and Blautia. In addition, a strain with neither outstanding antioxidant capacity nor adsorption capacity also reversed the decline in short-chain fatty acid levels caused by PFOA exposure. The ability of these strains to relieve gut microbiota dysbiosis partly explains the inconsistency between the capacity for antioxidant or PFOA adsorption and the ability of the strains to alleviate PFOA toxicity. The results indicate that the PFOA adsorption capacity and antioxidant capacity of LAB may be involved in the alleviation of PFOA liver toxicity. In addition, LAB could also alleviate liver damage caused by PFOA by adjusting the gut microbiota and short-chain fatty acid content. Therefore, some strains of LAB can be used as a potentially safe dietary supplement to relieve PFOA-induced liver damage.

Arsenic toxicokinetic modeling and risk analysis: Progress, needs and applications

Arsenic (As) poses unique challenges in PBTK model development and risk analysis applications. Arsenic metabolism is complex, adequate information to attribute specific metabolites to particular adverse effects in humans is sparse, and measurement of relevant metabolites in biological media can be difficult. Multiple As PBTK models have been published and used or adapted for use in various exposure and risk analysis applications. These applications illustrate the broad utility of PBTK models for exposure and dose-response analysis, particularly for arsenic where multi-pathway, multi-route exposures and multiple toxic effects are of concern. Arsenic PBTK models have been used together with exposure reconstruction and dose-response functions to estimate risk of specific adverse health effects due to drinking water exposure and consumption of specific foodstuffs (e.g. rice, seafood), as well as to derive safe exposure levels and develop consumption advisories. Future refinements to arsenic PBTK models can enhance the confidence in such analyses. Improved estimates for methylation biotransformation parameters based on in vitro to in vivo extrapolation (IVIVE) methods and estimation of interindividual variability in key model parameters for specific toxicologically relevant metabolites are two important areas for consideration.

Histological changes in female mice kidneys as a result of Valproic acid drug treatment

Valproic acid is a broad spectrum anti- convulsant drug, established as a long – term treatment for epilepsy and has toxic effect on kidney tissues. This study aimed to investigate the histological changes that may occur in the kidney in association with prolonged administration and overdose treatment of valproic acid. 35 albino mice were used, they were divided into four groups, group(I) included 5 animals and served as control group, group(II) included 10 animals and given progressive doses of valproic acid for ten weeks, starting with (15mg/kg/day) as minimum recommended dose and ending with (60mg/kg/day) as maximum recommended dose, group(III) included 10 animals and received an overdose (120mg/kg/day) for one week, group(IV) included 10 animals and treated exactly as group(II) then the animals were left for recovery for three weeks. The animals were sacrificed at the end of each period and the kidney tissue was excised. The drug induced many histological changes in kidney tissues, including inflammatory cellular infiltration, cell necrosis, cloudy swelling, hydropic degeneration, hemorrhage areas, oedema, and collagen deposition. The study concluded that valproic acid has multiple toxic effects on kidney tissues as far as the histological studies concerned and the effects were dependent on the dose and on the duration of treatment. Incomplete recovery was recorded after discontinuation of the drug.

Direct Detection of Viable but Non-culturable (VBNC) Salmonella in Real Food System by a Rapid and Accurate PMA-CPA Technique.

Salmonella enterica is a typical foodborne pathogen with multiple toxic effects, including invasiveness, endotoxins, and enterotoxins. Viable but nonculturable (VBNC) is a type of dormant form preserving the vitality of microorganisms, but it cannot be cultured by traditional laboratory techniques. The aim of this study is to develop a propidium monoazide-crossing priming amplification (PMA-CPA) method that can successfully detect S. enterica rapidly with high sensitivity and can identify VBNC cells in food samples. Five primers (4s, 5a, 2a/1s, 2a, and 3a) were specially designed for recognizing the specific invA gene. The specificity of the CPA assay was tested by 20 different bacterial strains, including 2 standard S. enterica and 18 non-S. enterica bacteria strains covering Gram-negative and Gram-positive isolates. Except for the two standard S. enterica ATCC14028 and ATCC29629, all strains showed negative results. Moreover, PMA-CPA can detect the VBNC cells both in pure culture and three types of food samples with significant color change. In conclusion, the PMA-CPA assay was successfully applied on detecting S. enterica in VBNC state from food samples.

New perspective on the regulation of acetylcholinesterase via the aryl hydrocarbon receptor.

Acetylcholinesterase (AChE, EC 3.1.1.7) plays important roles in cholinergic neurotransmission and has been widely recognized as a biomarker for monitoring pollution by organophosphate (OP) and carbamate pesticides. Dioxin is an emerging environmental AChE disruptor and is a typical persistent organic pollutant with multiple toxic effects on the nervous system. Growing evidence has shown that there is a significant link between dioxin exposure and neurodegenerative diseases and neurodevelopmental disorders, most of which involve AChE and cholinergic dysfunctions. Therefore, an in-depth understanding of the effects of dioxin on AChE and the related mechanisms of action might help to shed light on the molecular bases of dioxin impacts on the nervous system. In the past decade, the effects of dioxins on AChE have been revealed in cultured cells of different origins and in rodent animal models. Unlike OP and carbamate pesticides, dioxin-induced AChE disturbance is not due to direct inhibition of enzymatic activity; instead, dioxin causes alterations of AChE expression in certain models. As a widely accepted mechanism for most dioxin effects, the aryl hydrocarbon receptor (AhR)-dependent pathway has become a research focus in studies on the mechanism of action of dioxin-induced AChE dysregulation. In this mini-review, the effects of dioxin on AChE and the diverse roles of the AhR pathway in AChE regulation are summarized. Additionally, the involvement of AhR in AChE regulation during different neurodevelopmental processes is discussed. These AhR-related findings might also provide new insight into AChE regulation triggered by diverse xenobiotics capable of interacting with AhR.

Acrylamide alters the miRNA profiles and miR‐27a‐5p plays the key role in multiple tissues of rats

AbstractAcrylamide (AA) is the potential carcinogen, which can induce multiple toxic effects in laboratory animals and humans. So far, increasing attention have been paid to toxical mechanism and intervention measures of AA, however, these details and methods are still obscure. MicroRNAs (miRNAs) have been demonstrated to be involved in toxical functional mechanisms induced by chemicals in vivo or vitro. To explore novel target and mechanism of AA toxicity, a more detailed miRNA expression profiling study is needed. In this study, we established the short‐term high‐dose model of rats with the treatment of 35 mg/kg·b.w./day AA for 17 days, analyzed the miRNAs expression profiling in AA and control groups, and discovered the altered miRNA profiles in 11 tissues with AA treatment. Interestingly enough, the expression of miR‐27a‐5p were significantly up‐regulated in AA group, especially in bladder and hepar. Furthermore, we found miR‐27a‐5p increased in 11 tissues of long‐term low‐dose AA‐treated rats (3.5 mg/kg·b.w./day for 68 days). Therefore, these results revealed that AA changed miRNAs profiles in multiple tissues of SD rats for the first time and suggested that miR‐27a‐5p could be used as the target biomarker for the detection and interference of AA toxicity.

Multiple toxic effects of tetraconazole in Allium cepa L. meristematic cells.

The application of pesticides to get more agricultural products is increasing day by day. The use of a huge amount of pesticides raises public concerns about safety. Tetraconazole is a widely used and successful fungicide. Possible toxic, cytotoxic, and genotoxic effects of different doses of tetraconazole (1.00mg/L, 5.00mg/L, and 10.00mg/L) were evaluated on the meristematic cells of Allium cepa L. root tips by means of physiological, cytogenetic, biochemical, and anatomical parameters. EC50 value for tetraconazole in terms of growth inhibition was calculated as 6.7mg/L. Increasing doses of tetraconazole resulted in reduced germination ratio, root length, and weight gain. Total activities of superoxide dismutase (SOD) and catalase (CAT) enzymes as well as malondialdehyde (MDA) content were increased as a result of oxidative stress. As an evidence of genotoxicity, mitotic index (MI) level decreased, while scores for micronucleus (MN) and chromosomal aberrations (CAs) rose. In addition, various meristematic cell damages were detected in root tips of tetraconazole applied bulbs. As a result, the multiple toxic, cytotoxic, and genotoxic effects of tetraconazole fungicide were demonstrated through a wide range of parameters on A. cepa, which was found to be a versatile tool for testing hazardous pesticides.

Detoxification mechanisms of nickel sulfate in nematode Caenorhabditis elegans

Nickel is the most prevailing metal allergen with the highest sensitization rate among the “TOP 25” contact allergens and can affect about 15% of the human population. It is an essential trace metal in plants, animals, and humans. However, the environmental levels of nickel are considerably higher than what is needed for human life. Exposure to high levels of nickel can lead to skin allergies, lung fibrosis, and carcinogenesis. Few existing studies have closely examined the toxicity of nickel, let alone investigated the effective detoxification pathways. Here, we developed a high-throughput screening platform to comprehensively evaluate the nickel toxicity in wild-type C. elegans and explore the underlying detoxification mechanisms in transgenic nematodes. We demonstrated that nickel exerted multiple toxic effects on growth, brood size, feeding, and locomotion in C. elegans. Of which, brood size is the most sensitive endpoint. Nickel was found to first bind to phytochelatin (PC) after entering the worms’ body and this PC-Ni complex was further transported by the ABC transporter, CeHMT-1, into the coelomocytes for further detoxification. Our study also demonstrated that the high-throughput screening platform is a promising system for evaluation and investigation of the ecological risks of heavy metals.

Exposure to persistent organic pollutants during tooth formation: molecular mechanisms and clinical findings.

Persistent organic pollutants (POPs) constitute a relevant part of environmental pollution. POPs are chemical compounds that persist for a long time in the environment, bio-accumulate in the human body and determine significant adverse consequences to human health. The characteristics of these substances are lipo-affinity, semi-volatility and resistance to the degradation processes. Results deriving from several different studies attest that exposure to the main classes of POPs results in multiple toxic effects on humans and experimental animal models. Among the various alterations caused by exposition to and bio-accumulation of POPs, there are abnormalities in tooth formation and related hard dental tissue structure, especially enamel. This review aimed to describe the close association between the exposure of these compounds during the development of the tooth germ and the occurrence of tooth structural anomalies. Indeed, structural defects of the enamel have as possible consequences higher susceptibility of the tooth to caries disease and higher fragility of the crown to the occlusal trauma.

ANTI-INFLAMMATORY AND ANTIOXIDANT PROPERTIES OF ECBALLIUM ELATERIUM FRUIT JUICE AGAINST CYCLOPHPSPHAMIDE INDUCED HEPATOTOXICITY IN RATS

ABSTRACT Background: Cyclophosphamide (CP) is one of the chemotherapeutic and immunosuppressive agents. It has multiple toxic effects, particularly hepatotoxicity. Ecballium elaterium (EE) plant is found in the Mediterranean counties. It has been used as a traditional medicine. Objectives: This work aimed to evaluate the ameliorative effect of EE fruit juice on hepatotoxicity induced by CP in rats. Material and methods: 28 male rats were divided into equal 4 groups: control group, EE group (0.2 mL/kg orally for 10 days), CP group (2 doses of 150 mg/kg intraperitoneally in the first 2 days), and EE plus CP group. Biochemical analysis for serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin and albumin were carried out. Hepatic oxidant/antioxidant markers; glutathione (GSH), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), and lipid peroxidation product; malondialdehyde (MDA) in addition to pro-inflammatory mediators; tumor necrosis factor-α (TNF- α), interleukin (IL-1β) and IL-6 were evaluated. Histopathological examination of the liver was investigated. Results: Serum liver enzymes and total bilirubin were significantly increased with a decrease in albumin in the CP treated group compared to control group. CP induced depletion of oxidative stress defensive pathways with increased MDA levels. The examined pro-inflammatory mediators were significantly elevated as compared to control group with disruption of hepatic histopathology. All these hepatic disturbances were ameliorated by administration of EE fruit juice with CP. Conclusion: Administration of EE fruit juice ameliorates the hepatotoxicity induced by CP through its antioxidant and anti-inflammatory activity.

Abamectin induces cytotoxicity via the ROS, JNK, and ATM/ATR pathways.

Abamectin has been widely used in agriculture and animal husbandry. It has been shown that abamectin exposure could induce multiple toxic effects on non-target organisms, but the underlying mechanism is still largely unknown. In the current study, the mechanism of abamectin-induced cytotoxicity was investigated in mouse embryonic fibroblast cells. Abamectin treatment could cause oxidative stress in cells (beginning at 0.4 μg/ml, 0.5 μM) and the ROS overproduction was mainly induced by the impacts of abamectin on the activities of CAT (beginning at 4.4 μg/mL, 5 μM), SOD (beginning at 8.7 μg/mL, 10 μM), GPx (beginning at 4.4 μg/mL, 5 μM), and contents of GSH (beginning at 4.4 μg/mL, 5 μM), which are important components of the ROS elimination pathway in mammal cells. Abamectin could impair DNA integrity (as demonstrated by increased 8-OHdG/dG ratio) in cells, even at environmental level (0.4 μg/mL, NOAEL), and abamectin-induced oxidative stress was one of the main reasons for the DNA damage that occurred in cells. Moreover, pretreatment with the inhibitor of JNK and ATM/ATR signaling pathway could partially rescue the decreased cell viability, indicating that oxidative stress and DNA damage might be involved in abamectin-induced cytotoxicity. These findings could provide new insights into the mechanism of abamectin-induced cytotoxicity and should be useful for a more comprehensive assessment of the adverse effects of abamectin.

Role of procalcitonin use in the management of sepsis.

Important aspects of sepsis management include early diagnosis as well as timely and specific treatment in the first few hours of triage. However, diagnosis and differentiation from non-infectious causes often cause uncertainties and potential time delays. Correct use of antibiotics still represents a major challenge, leading to increased risk for opportunistic infections, resistances to multiple antimicrobial agents and toxic side effects, which in turn increase mortality and healthcare costs. Optimized procedures for reliable diagnosis and management of antibiotic therapy has great potential to improve patient care. Herein, biomarkers have been shown to improve infection diagnosis, help in early risk stratification and provide prognostic information which helps optimizing therapeutic decisions ("antibiotic stewardship"). In this context, the use of the blood infection marker procalcitonin (PCT) has gained much attention. There is still no gold standard for the detection of sepsis and use of conventional diagnostic approaches are restricted by some limitations. Therefore, additional tests are necessary to enable early and reliable diagnosis. PCT has good discriminatory properties to differentiate between bacterial and viral inflammations with rapidly available results. Further, PCT adds to risk stratification and prognostication, which may influence appropriate use of health-care resources and therapeutic options. PCT kinetics over time also improves the monitoring of critically ill patients with sepsis and thus influences decisions regarding de-escalation of antibiotics. Most importantly, PCT helps in guiding antibiotic use in patients with respiratory infection and sepsis by limiting initiation and by shortening treatment duration. To date, PCT is the best studied biomarker regarding antibiotic stewardship. Still, further research is needed to understand optimal use of PCT, also in combination with other remerging diagnostic tests for most efficient sepsis care.

Selenium nanovirus and its cytotoxicity in selenite-exposed higher living organisms

Selenium (Se) is an essential micronutrient in living organisms, having a narrow margin between essential and potentially toxic intake/exposure. Thus, the biochemistry of Se in living organisms must be studied in-depth to determine the underlying mechanism of Se cytotoxicity. In this study, we report the emergence of selenium nanovirus (SeNVs) in selenite-exposed fish (freshwater and saltwater) and plants (dryland) and its toxicity in them. SeNVs were found in both the abdomen and tail of Oryzias melastigma and saltwater Rhodeus ocellatus, which led to their death. The occurrence of the intracellular assembly of SeNVs was observed in the roots and leaves of corn Zea mays, but not in those of Limnobium laevigatum. SeNVs led to the death of Z. mays but caused chronic toxicity in L. laevigatum. SeNVs should be a system or structure that dissipates the intracellular redox gradients of the host cells, with simple information consisting Se–O, Se–N, or Se–S bond, that would ensure elemental Se ligand binding with nearly specific biomolecules in host cells, thereby maintaining their composition and stabilizing their structure. The multiple toxic effects of Se, therefore, could be the consequence of increase of entropy in the host cells caused by the intracellular assembly of SeNVs. This study may provide an insight into the underlying mechanism of Se in environmental toxicology and its applications in human health.

Covalent modification of phosphatidylethanolamine by 4-hydroxy-2-nonenal increases sodium permeability across phospholipid bilayer membranes

Reactive aldehydes (RAs), such as 4-hydroxy-2-nonenal (HNE) and 4-oxo-2-nonenal (ONE), produced by cells under conditions of oxidative stress, were shown to react with phosphatidylethanolamine (PE) in biological and artificial membranes. They form RA-PE adducts, which affect the function of membrane proteins by modifying various biophysical properties of the membrane. The ratio of protein to lipid in biological membranes is different, but can reach 0.25 in the membranes of oligodendrocytes. However, the impact of RA-PE adducts on permeability (P) of the neat lipid phase and molecular mechanism of their action are poorly understood. In this study, we showed that HNE increased the membrane P for ions, and in particular for sodium. This effect depended on the presence of DOPE, and was not recorded for the more toxic compound, ONE. Molecular dynamics simulations suggested that HNE-PE and ONE-PE adducts anchored different positions in the lipid bilayer, and thus changed the membrane lipid area and bilayer thickness in different ways. Sodium permeability, calculated in the presence of double HNE-PE adducts, was increased by three to four orders of magnitude when compared to PNa in adduct – free membranes. A novel mechanism by which HNE alters permeability of the lipid membrane may explain the multiple toxic or regulative effects of HNE on the function of excitable cells, such as neurons, cardiomyocytes and neurosensory cells under conditions of oxidative stress.

Accumulation of different shapes of microplastics initiates intestinal injury and gut microbiota dysbiosis in the gut of zebrafish

Different shapes of microplastics are widely detected in the environment and organisms and most of them remain in the gut. However, the influences of shapes on the bioaccumulation and toxicity of microplastics in the gut are largely unknown. Three shapes (bead, fragment, and fiber) of microplastics of comparable size in one dimension were prepared to exposure to zebrafish. The accumulation and toxicities of microplastics in the gut were detected. Shape-dependent accumulation in the gut was observed with the order of fibers (8.0 μg/mg) > fragments (1.7 μg/mg) > beads (0.5 μg/mg). The accumulation of microplastics caused multiple toxic effects in fish intestine, including mucosal damage, and increased permeability, inflammation and metabolism disruption. Based on these toxic effects, microplastic fibers resulted in more severe intestinal toxicity than microplastic fragments and beads did. Furthermore, microplastics also induced gut microbiota dysbiosis and specific bacteria alterations, which will provide novel insights into the potential mechanism of microplastics causing intestinal toxicities in fish. Our results also suggested that shape-depended effects should not be ignored in the health risk assessment of microplastics.

Downregulations of placental fatty acid transporters during cadmium-induced fetal growth restriction

Cadmium (Cd) is one of the environmental pollutants, which has multiple toxic effects on fetuses and placentas. Placental fatty acid (FA) uptake and transport are critical for the fetal and placental development. We aimed to analyze the triglyceride (TG) level, the expression patterns of several key genes involved in FA uptake and transport, and the molecular mechanisms for the altered gene expressions in placentas in response to Cd treatment. Our results showed that the placental TG level was significantly decreased in the Cd-exposed placentas. Fatty acid transporting protein 1 (FATP1), FATP6 and fatty acid binding protein 3 (FABP3) were significantly down-regulated in the placentas from Cd-exposed mice. The expression level of phospho-p38 MAPK was increased by Cd treatment, while the protein level of total p38 MAPK remained unchanged. The expression levels of peroxisome proliferator-activated receptor-γ (PPAR-γ) and the hypoxia-inducible factor-1α (HIF-1α) were significantly decreased in the Cd-exposed placentas. The methylation levels of the promoter regions of FATP1, FATP6 and FABP3 showed no significant differences between the treatment and control groups. In addition, the circulating non-esterified fatty acid (NEFA), total cholesterol (TC), and TG levels were not decreased in the maternal serum from the Cd-exposed mice. Therefore, our results suggest Cd exposure dose not reduce the maternal FA supply, but reduces the placental TG level. Cd treatment also downregulates the placental expressions of FATP1, FATP6 and FABP3, respectively associated with p38-MAPK, p38 MAPK/PPAR-γ and HIF-1α pathways.

Quinoline derivatives producing Pseudomonas aeruginosa H6 as an efficient bioherbicide for weed management

Abstract Regular application of weedicides has led to multiple toxic effects on human health, environment, and food safety which also facilitated an emergence of weed resistance. Development of bioherbicides using microorganisms has attained considerable attention nowadays for weed management in agricultural fields. In the present study, a rhizospheric bacteria, H6, showing a weedicide efficacy was discovered from the rhizosphere of Momordica charantia. By classical methods and 16S ribosomal DNA phylogenesis, H6 was identified as Pseudomonas aeruginosa. The weedicidal prospective of the secondary metabolites bred by H6 was investigated. Broth, supernatant culture and crude extract of H6 showed high inhibition activity in Pennisetum purpureum, Oryza sativa, Pisum sativa, and Amaranthus spinosum. In general, germination inhibitions of selected weeds were shown by metabolites of the strain H-6. Metabolite identified from strain H6 shows the presence of antifungal and herbicidal compounds. The herbicidal metabolites produced by Pseudomonas aeruginosa H6, was determined by GC- MS analysis. The results revealed that quinoline derivatives which are highly toxic to the target weeds were the distinctive metabolite found within Pseudomonas aeruginosa H6, making it a potential bioherbicide against weed growth. Hence, the results of the present investigation suggest that Pseudomonas aeruginosa H6 can be a suitable alternative to agrochemicals for weed management.

Probiotic Bacillus subtilis CW14 reduces disruption of the epithelial barrier and toxicity of ochratoxin A to Caco-2 cells

The multiple toxic effects of ochratoxin A (OTA) are a threat for human and animal. This study aimed to examine whether B. subtilis CW14 protected against OTA-induced barrier disruption and cell damage to Caco-2 cells. The results showed that Caco-2 cells treated with OTA led to microvilli disruption, tight junction protein (ZO-1 and claudin-1) damage, and inhibition of cell proliferation by arresting the cell cycle in the G2/M phase that promoted apoptosis. The treatment of B. subtilis CW14 mitigated the tight junction injury by improving ZO-1 protein expression, and it reduced apoptosis that was induced by OTA. Furthermore, transcriptome analysis indicated that OTA down-regulated genes that involved in the tight junction, cell cycle, and apoptosis-related signaling pathways. B. subtilis CW14 may have protected the ZO-1 protein by activating the toll-like receptor signaling pathway, and it reduced OTA damage by down-regulating the death receptor genes and up-regulating the DNA repair genes. These findings demonstrated the importance of B. subtilis CW14 in the regulation of tight junction proteins and in reducing death of intestinal epithelial cells. Thus, B. subtilis CW14 is a potential candidate as a food additive to protect against intestinal damage.