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1.
Crit Rev Toxicol ; 54(3): 194-213, 2024 03.
Article in English | MEDLINE | ID: mdl-38470098

ABSTRACT

Neonicotinoid pesticides are utilized against an extensive range of insects. A growing body of evidence supports that these neuro-active insecticides are classified as toxicants in invertebrates. However, there is limited published data regarding their toxicity in vertebrates and mammals. the current systematic review is focused on the up-to-date knowledge available for several neonicotinoid pesticides and their non-acute toxicity on rodents and human physiology. Oral lethal dose 50 (LD50) of seven neonicotinoids (i.e. imidacloprid, acetamiprid, clothianidin, dinotefuran, thiamethoxam, thiacloprid, and nitenpyram) was initially identified. Subsequently, a screening of the literature was conducted to collect information about non-acute exposure to these insecticides. 99 studies were included and assessed for their risk of bias and level of evidence according to the Office of Health and Translation (OHAT) framework. All the 99 included papers indicate evidence of reproductive toxicity, hepatotoxicity, nephrotoxicity, neurotoxicity, immunotoxicity, and oxidative stress induction with a high level of evidence in the health effect of rodents and a moderate level of evidence for human health. The most studied type of these insecticides among 99 papers was imidacloprid (55 papers), followed by acetamiprid (22 papers), clothianidin (21 papers), and thiacloprid (11 papers). While 10 of 99 papers assessed the relationship between clothianidin, thiamethoxam, dinotefuran, and nitenpyram, showing evidence of liver injury, dysfunctions of oxidative stress markers in the reproductive system, and intestinal toxicity. This systematic review provides a comprehensive overview of the potential risks caused by neonicotinoid insecticides to humans and rodents with salient health effects. However, further research is needed to better emphasize and understand the patho-physiological mechanisms of these insecticides, taking into account various factors that can influence their toxicity.


Subject(s)
Guanidines , Insecticides , Thiazines , Thiazoles , Animals , Humans , Thiamethoxam , Insecticides/toxicity , Oxazines/toxicity , Neonicotinoids/toxicity , Nitro Compounds/toxicity , Risk Assessment , Mammals
2.
J Oleo Sci ; 72(2): 139-151, 2023 Feb 04.
Article in English | MEDLINE | ID: mdl-36631100

ABSTRACT

Due to over worldwide use of frying oil, and due to its oxidation and deterioration after the usage for short time, huge oil amounts are wasted. So, most attempts are aimed to increase oil stability. Quercetin is a common name for the lipophobic strong natural phenolic antioxidant 2-(3,4-Dihydroxyphenyl)-5,7-dihydroxy-4H-1-benzopyran-4-one. Thus, its solubility had been improved by converting it to a lipophilic compound via its appending to a fatty acid residue. So, regioselectively 2-(3,4-Dihydroxyphenyl)-5,7-dihydroxy-3-[Hexadecanyl]oxychromen-4-one commonly named as (Quercetin-3-palmitate) was synthesized. The formed compound was confirmed based on its elemental analysis and spectral data (IR, 1H NMR and MS). The partition coefficient of Quercetin-3-palmitate in octanol/water (k) was determined and compared to that of palmitic acid and quercetin individually to prove its solubility enhancement. Its radical scavenging activity was then tested. The effect of this new antioxidant compound on the oil stability was studied through the frying process. All physical and chemical parameters of this oil were considered before and after the frying process compared to another reference antioxidant (TBHQ) and control sample. The safety of this compound was determined by acute oral toxicity using albino mice. The liver and kidney functions of these mice were also examined. The results showed non-significant change. A sensory evaluation of the fried potato chips has been done. The results showed that the properties of the potato chips were improved by adding Quercetin-3-palmitate to the oil. Thus, good protection against frying oils oxidation was achieved via the addition of Quercetin-3-palmitate. The Quercetin-3-palmitate effectiveness is mainly attributed to its stability at high temperatures. Moreover, Quercetin-3-palmitate was found to be a safe compound according to an acute lethal toxicity test. Consequently, it can be used as a food additive.


Subject(s)
Antioxidants , Quercetin , Mice , Animals , Antioxidants/analysis , Quercetin/analysis , Palmitates , Oils/analysis , Cooking/methods , Hot Temperature
3.
Environ Technol ; 44(14): 2148-2156, 2023 Jun.
Article in English | MEDLINE | ID: mdl-34962184

ABSTRACT

Organophosphates (OPs) and synthetic pyrethroids (SPs) are the most popular broad spectrum pesticides, used in agriculture as they have a strong pesticidal activity while also being biodegradable in the environment. The present study aimed to demonstrate the effects of these pesticides on the Acetylcholinesterase (AChE) activity in brain, gills and body muscles of Oreochromis niloticus - an important enzyme for the assessment and biomonitoring pollution caused by neurotoxins in the environment. The fish were exposed for 24 and 48 h to the LC0 concentrations of the malathion (1.425 mg/L), the chlorpyrifos (0.125 mg/L) and the λ-cyhalothrin (0.0039 mg/L), respectively. The activity of the AChE was significantly increased (p < 0.05) at 24 h and decreased at 48 h (except for the chlorpyrifos-treated brain and gills while tissues had shown no activity at 48 h's exposure) in all pesticides-treated tissues. The maximum increase in the activity and inhibition in the AChE activity were recorded as +92% and -52% in the chlorpyrifos and the lambda-cyhalothrin exposed brain tissues, respectively. Thus, the alterations in the AChE activities indicated that the applied pesticides are highly neurotoxic to fish and the enzyme (AChE) could be used as a useful biomarker for estimation of water pollution.


Subject(s)
Chlorpyrifos , Cichlids , Pesticides , Pyrethrins , Water Pollutants, Chemical , Animals , Pesticides/toxicity , Chlorpyrifos/toxicity , Acetylcholinesterase , Pyrethrins/toxicity , Biomarkers , Water Pollutants, Chemical/toxicity
4.
Sci Total Environ ; 859(Pt 1): 160077, 2023 Feb 10.
Article in English | MEDLINE | ID: mdl-36372173

ABSTRACT

Cyprosulfamide is a herbicide safener that works against the injurious effects of herbicides such as isoxaflutole, dicamba, nicosulfuron, tembotrione, thiencarbazone-methyl. However, its sorption behaviour in soils and toxicity to aquatic organisms are yet to be thoroughly examined. This study determined the octanol-water partition coefficient, sorption properties, acute and chronic toxic effects, and potency of cyprosulfamide to the cladoceran water flea (Daphnia magna). The influence of soil properties such as organic carbon content, cation exchange capacity, pH, and field capacity on adsorption and desorption properties were also examined. The Log Kow (0.55) of cyprosulfamide was less than that of some other safeners, such as benoxacor or furilazole, found in aquatic environments. The sorption of cyprosulfamide to the soil was driven by pH, so sorption decreased with an increase in pH. Other characteristics, such as cation exchange capacity (CEC), organic carbon content, and field capacity, do not directly correlate with the distribution coefficient. Cyprosulfamide generally has a low affinity for soil and is thus mobile and prone to transport to surrounding surface waters. No lethality was observed at the highest concentration (120 mg/L) tested for acute toxicity to D. magna; hence the LC50 will be >120 mg/L. During chronic exposures, cyprosulfamide caused adverse effects at a concentration of 120 mg/L on the number of neonates and brood size. The death rate for the chronic study was a function of concentration and increased with days of exposure. Cyprosulfamide is unlikely to cause lethality to D. magna at relevant environmental concentrations.


Subject(s)
Herbicides , Soil Pollutants , Herbicides/toxicity , Herbicides/chemistry , Soil , Soil Pollutants/chemistry , Adsorption , Carbon
5.
Toxicol Mech Methods ; 33(5): 364-377, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36345843

ABSTRACT

The indiscriminate and rampant use of pesticides has raised serious concerns regarding their toxic impact on non-target organisms which underlines need for the development of an effective antidote. Metabolic activation of organophosphate pesticides by the phase I enzyme, cytochrome P450 plays a key role in influencing pesticide-toxicity. In this study, we have investigated the effect of environmentally relevant malathion concentration (100 µg/L) alone and in combination with vitamin B12 on the expression of genes related to xenobiotic metabolism such as CYP enzymes, PgP and the key oxidative stress responsive transcription factor, Nrf2 in zebra fish liver and brain. Expressions of Nrf2-trasncribed antioxidant genes and their activities were also measured. Administration of vitamin B12 successfully revived motor functions by modulation of AchE activity. Mechanistically, vitamin B12 was demonstrated to alleviate oxidative stress which was accompanied by decreased phase-I enzyme cyp3c1 and increased pgp expressions.


Subject(s)
Antioxidants , Malathion , Pesticides , Vitamin B 12 , Animals , Cytochrome P-450 Enzyme System/genetics , Cytochrome P-450 Enzyme System/metabolism , Malathion/toxicity , NF-E2-Related Factor 2/metabolism , Oxidative Stress , Vitamin B 12/pharmacology , Zebrafish/metabolism , Antioxidants/pharmacology
6.
Magn Reson Chem ; 61(12): 728-739, 2023 12.
Article in English | MEDLINE | ID: mdl-36137948

ABSTRACT

Superparamagnetic iron oxide nanoparticles (SPIONs) are a contaminant of emerging interest, often used in the medical field as an imaging contrast agent, with additional uses in wastewater treatment and as food additives. Although the use of SPIONs is increasing, little research has been conducted on the toxic impacts to living organisms beyond traditional lethal concentration endpoints. Daphnia magna are model organisms for aquatic toxicity testing with a well understood metabolome and high sensitivity to SPIONs. Thus, as environmental concentrations continue to increase, it is becoming critical to understand their sub-lethal toxicity. Due to the paramagnetic nature of SPIONs, a range of potential nuclear magnetic resonance spectroscopy (NMR) experiments are possible, offering the potential to probe the physical location (via imaging), binding (via relaxation weighted spectroscopy), and the biochemical pathways impacted (via in vivo metabolomics). Results indicate binding to carbohydrates, likely chitin in the exoskeleton, along with a decrease in energy metabolites and specific biomarkers of oxidative stress. The holistic NMR framework used here helps provide a more comprehensive understanding of SPIONs impacts on D. magna and showcases NMR's versatility in providing physical, chemical, and biochemical insights.


Subject(s)
Daphnia , Magnetic Resonance Imaging , Animals , Daphnia/metabolism , Magnetic Resonance Spectroscopy/methods , Metabolomics/methods , Magnetic Iron Oxide Nanoparticles
7.
Environ Sci Pollut Res Int ; 29(60): 90259-90271, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35864402

ABSTRACT

Acid mine drainage (AMD) involves complex mixtures of metals and hydrogen ions that can be highly toxic to the biota. Assessing the effects of AMD to aquatic stages of amphibians is key, as this group constitutes the vertebrate class with the highest proportion of species considered as threatened. Thus, the present work aimed at assessing the sensitivity of two aquatic life stages of the green frog Pelophylax perezi to an AMD originated from a cupric-pyrite mine. Embryos (Gosner stages 10-11) and tadpoles (Gosner stages 20-21) of P. perezi were exposed, for 96 h, to six AMD dilutions (1.39% to 7.5%). Endpoints involving responses at different levels of biological organization were monitored: mortality, malformations, hatching rates, body length and growth rate, enzymatic activity related with detoxification metabolism (glutathione S-transferase), and histopathologies (anatomical structures of the digestive, respiratory, and excretory systems). Embryos presented high mortality and malformation rates at AMD levels equal or above 5.36%, as well as premature hatching at 1.95% of AMD or higher. A significant reduction in body length and growth rate occurred in embryos and tadpoles exposed to 1.95% or higher levels of AMD, respectively. At the histological level, several abnormalities were observed for AMD-exposed tadpoles in a variety of tissues. One of the most noticeable histological changes occurred in the intestine that exhibited papillary epithelial hyperplasia along with a yellowish content and was more pronounced in tadpoles exposed to higher AMD levels. FEmbryos were more sensitive to lethal levels of AMD than tadpoles, suggesting embryos as a useful model life stage when performing amphibian risk assessment of mine drainage. Furthermore, AMD was highly toxic for P. perezi aquatic life stages since levels as low as 1.95% induced lethal effects. These results emphasize the importance of implementing efficient remediation methodologies for AMD, given its high toxicity.

8.
Environ Int ; 164: 107264, 2022 06.
Article in English | MEDLINE | ID: mdl-35489111

ABSTRACT

The presence and potential toxicity of nanoplastics (NPs) in aquatic ecosystems is an issue of growing concern. Although many studies have investigated the adverse effects of short-term exposure to high concentrations of NPs to aquatic organisms, the information on the consequences caused by the administration of low NPs concentrations over long-term exposure is limited. The present study aimed at investigating the effects induced by a long-term exposure (21-days) to two sub-lethal concentrations of polystyrene nanoplastics (PS-NPs; 0.05 and 0.5 µg/mL) on Daphnia magna. A multi-level approach was performed to assess potential sub-individual (i.e., molecular and biochemical) and individual (i.e., behavioural) adverse effects. At molecular level, the modulation of the expression of genes involved in antioxidant defence, response to stressful conditions and specific physiological pathways was investigated. Oxidative stress (i.e., the amount of pro-oxidants, the activity of antioxidant and detoxifying enzymes and lipid peroxidation) and energetic (i.e., protein, carbohydrate, lipid and total caloric content) biomarkers were applied to assess effects at the biochemical level, while swimming activity was measured to monitor changes in individual behavior. Although the 21-days exposure to PS-NPs induced a slight modulation of gene involved in oxidative stress response, biochemical analyses showed that D. magna individuals did not experience an oxidative stress condition. Significant changes in energy reserves of individuals exposed for 21 days to both the PS-NPs concentrations were observed, but no alterations of swimming activity occurred. Our results highlighted that the exposure to low concentrations of PS-NPs could pose a limited risk to D. magna individuals and suggested the importance of a multi-level approach to assess the risks of NPs on aquatic organisms.


Subject(s)
Daphnia , Water Pollutants, Chemical , Animals , Antioxidants/metabolism , Daphnia/metabolism , Ecosystem , Microplastics/toxicity , Polystyrenes/analysis , Polystyrenes/chemistry , Polystyrenes/toxicity , Water Pollutants, Chemical/analysis
9.
Aquat Toxicol ; 247: 106172, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35468410

ABSTRACT

In aquatic arthropods, molting is a pivotal physiological process for normal development, but it may also expose them to higher risks from xenobiotics, because the organism may take up additional water during that time. This study aimed to assess the effects of molting on bioconcentration and survival after 96-h exposure to insecticide fipronil with or without oxygenase (CYP450s) inhibitor piperonyl butoxide (PBO) of two estuarine resident marine crustacean species: the sand shrimp Crangon uritai and the kuruma prawn Penaeus japonicus, with 96-h LC50 value of fipronil = 2.0 µg/L and 0.2 µg/L, respectively. Two graded concentrations included group high (H) (equivalent to the 96-h LC50 values) and low (L) (one-tenth of the H group concentration). Molting and survival were individually checked, and internal concentrations of fipronil and its metabolites (fipronil desulfinyl, fipronil sulfide, fipronil sulfone) were measured. The results showed that, only fipronil and fipronil sulfone were detected from organism, and that internal concentrations of these insecticides in molted specimens were higher than those of unmolted ones but comparable with those of dead ones. Accordingly, mortality was more frequent in molted specimens than those that were unmolted. Furthermore, involvement of oxygenase and higher lethal body burden threshold may confer higher tolerance to fipronil in sand shrimp than in the kuruma prawn. This study is the first to demonstrate that the body-residue-based approach is useful for deciphering the causal factors underlying fipronil toxicity, but highlights the need to consider physiological factors in arthropods, which influence and lie beyond body burden, molting and drug metabolism.


Subject(s)
Insecticides , Penaeidae , Water Pollutants, Chemical , Animals , Insecticides/toxicity , Molting , Oxygenases/pharmacology , Pyrazoles , Water Pollutants, Chemical/toxicity
10.
Toxicol Res ; 38(2): 187-194, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35419277

ABSTRACT

Organophosphates and synthetic pyrethroid insecticides have been commonly used in public health and agriculture. The present study aimed to evaluate the sub-lethal effects of organophosphates and synthetic pyrethroid insecticides on transaminases: glutamate oxaloacetate/aspartate transaminase (AST) and glutamate pyruvate/alanine transaminase (ALT) in Oreochromis niloticus. Fish were exposed to malathion (OP), chlorpyrifos (OP) and λ-cyhalothrin (synthetic pyrethroid) at sub-lethal concentrations of 1.425, 0.125 and 0.0039 ppm, respectively for 24 and 48 h. AST and ALT activities were shown to be remarkably (p < 0.05) decreased and increased, respectively in O. niloticus treated with the insecticides. The highest and lowest inhibition in AST level were noted as -12.2% and -12.2% in chlorpyrifos and λ-cyhalothrin 24 h treated fish samples, respectively. The highest and lowest elevation in ALT level were recorded as + 313% and 237% in 48 h chlorpyrifos and 24 h malathion treated fish samples, respectively. This indicates that the insecticides used in this study did not result in death but in changes in AST and ALT enzyme activities. Therefore, organophosphates (malathion, chlorpyrifos) and synthetic pyrethroid (λ-cyhalothrin) insecticides are toxic to fishes and could affects their survival in their natural habitat.

11.
Environ Sci Pollut Res Int ; 29(18): 27534-27547, 2022 Apr.
Article in English | MEDLINE | ID: mdl-34981374

ABSTRACT

Recent advances in nanotechnology have allowed the encapsulation of hazardous antifouling (AF) biocides in silica mesoporous nanocapsules (SiNC) reducing their short-term toxicity. However, the chronic effects of such novel nanoadditives remain understudied. The present study aimed to assess short- and long-term sub-lethal effects of soluble forms (DCOIT and Ag) and nanostructured forms (SiNC-DCOIT and SiNC-DCOIT-Ag) of two AF biocides and the "empty" nanocapsule (SiNC) on juveniles of Crassostrea gigas after 96 h and 14 days of exposure. Juvenile oysters exposed for a short period to free DCOIT and AgNO3 presented worse physiological status comparing with those exposed to the nanostructured forms. The long-term exposure to DCOIT and Ag+ caused an extensive biochemical impairment comparing with the tested nanomaterials, which included oxidative damage, activation of the antioxidant defense system, and neurotransmission impairment. Despite the negative effects mostly observed on the health condition index and AChE, the encapsulation of the abovementioned AF biocides into SiNC seems to be a technological advantage towards the development of AF nanoadditives with lower long-term toxicity comparing with the soluble forms of such biocides.


Subject(s)
Biofouling , Crassostrea , Disinfectants , Nanostructures , Water Pollutants, Chemical , Animals , Biofouling/prevention & control , Disinfectants/toxicity , Nanostructures/toxicity , Oxidative Stress , Water Pollutants, Chemical/toxicity
12.
Article in English | MEDLINE | ID: mdl-34298192

ABSTRACT

Water hardness above the optimal level can incite toxic effects in fish, which are often species specific. Hence, we aimed at obtaining insights on the potential effects of elevated water hardness as well as coping strategies in channel catfish (Ictalurus punctatus). First, a toxicity assay was performed where the 96 h-LC50 was calculated as 4939 mg/L CaCO3. Thereafter, to gain knowledge on the underlying adaptive strategies to high water hardness, fish were exposed to seven hardness levels (150, 600, 1000, 1500, 2000, 3000 and 4000 mg/L CaCO3 at pH 8.15) for 15 days. Results showed that branchial activities of Ca2+-ATPase and Na+/K+-ATPase, which facilitate Ca2+ uptake, reduced starting respectively from 1000 mg/L and 1500 mg/L CaCO3. Nevertheless, Ca2+ burden in plasma and tissue (gills, liver and intestine) remained elevated. Hardness exposure also disturbed cations (Na+, K+, Mg2+) and minerals (iron and phosphorus) homeostasis in a tissue-specific and dose-dependent manner. Both hemoglobin content and hematocrit dropped significantly at 3000-4000 mg/L CaCO3, with a parallel decline in iron content in plasma and gills. Muscle water content rose dramatically at 4000 mg/L CaCO3, indicating an osmo-regulation disruption. Higher hardness of 3000-4000 mg/L CaCO3 also incited a series of histopathological modifications in gills, liver and intestine; most likely due to excess Ca2+ accumulation. Overall, these data suggest that channel catfish can adapt to a wide range of elevated hardness by modulating Ca2+ regulatory pathways and histomorphological alterations, however, 1500 mg/L CaCO3 and above can impair the performance of this species.


Subject(s)
Calcium/metabolism , Ictaluridae/metabolism , Ions/metabolism , Sodium-Potassium-Exchanging ATPase/metabolism , Water/metabolism , Animals , Catfishes/metabolism , Fresh Water/chemistry , Gills/metabolism , Hematocrit , Homeostasis , Intestines/enzymology , Liver/enzymology , Water Pollutants, Chemical/toxicity
13.
Chemosphere ; 267: 129279, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33352371

ABSTRACT

In this study, laboratory experiments have addressed the acute toxicity of two common mycotoxins, deoxynivalenol (DON) and zearalenone (ZON), in a range of freshwater organisms (including rotifers Brachionus calyciflorus, insects Chironomus riparius (larvae), crustaceans Daphnia pulex and Thamnocephalus platyurus, cnidarians Hydra vulgaris, molluscs Lymnaea stagnalis (embryos) and Protozoa Tetrahymena thermophila). Acute EC50 values highlight crustaceans as the most sensitive organisms to DON, with T. platyurus having a 24 h EC50 of 0.14 and D. magna having a 48 h EC50 of 0.13 mg DON/L. During exposures to ZON, H. vulgaris and L. stagnalis embryos showed the highest sensitivity; mortality EC50 values were 1.1 (96 h) and 0.42 mg ZON/L (7 d), respectively. Combining these novel invertebrate toxicity results, along with recent published data for freshwater plant and fish toxicity for analysis of Species Sensitivity Distributions, provides freshwater HC5 values of 5.2 µg DON/L and 43 µg ZON/L, respectively. Using highest reported environmental concentrations and following REACH guidelines, risk ratios calculated here show the risk of ZON to freshwater organisms is low. In contrast, DON may periodically because for concern in streams subject to high agricultural run-off, likely during certain times of year where cereal crops are susceptible to higher fungal infections rates and may pose increased risks due to climate change.


Subject(s)
Mycotoxins , Trichothecenes , Zearalenone , Animals , Fresh Water , Trichothecenes/toxicity , Zearalenone/toxicity
14.
Environ Sci Pollut Res Int ; 28(11): 13105-13111, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33174171

ABSTRACT

Chlorpyrifos (ChF) is an organophosphate pesticide that is widely used in agricultural fields and indoor for controlling pests. Aquatic ecosystems are the recipients of various pesticide residues due to leaching spray drift and agricultural runoff and pose toxicity for aquatic organisms. Therefore, the current study was designed to investigate the oxidative stress enzymes and histological alterations in the vital organs of tilapia due to ChF exposure. LC50 (24 h) was calculated as 52.78 µg/l by exposing tilapia with different acute concentrations of ChF. For assessment of sub-lethal toxicity of ChF, the fish were divided into four groups (ChF1, ChF2, ChF3, and control group). ChF1 group was treated with 1/15th of LC50, whereas ChF2 and ChF3 groups were treated with 1/10th and 1/5th of LC50, respectively for 14 days. After that, ChF induced changes in oxidative stress enzymes and histological alterations were evaluated. It was found that the level of glutathione S-transferase (GST), catalase (CAT), and superoxide dismutase (SOD) increased significantly in the liver of ChF-treated tilapia. Histological study of liver tissues showed an increased number of Kupffer cells, hydropic degeneration, necrosis, and hemorrhage. In the spleen of treated fish, increased melanomacrophage centers, necrosis, and congestion were detected. Disorganized muscle fibers, cardiac muscle fiber degeneration, and coagulative necrosis were observed in the heart of ChF-treated fish. It is concluded that sub-lethal concentrations of ChF can induce oxidative stress and histological alterations in the tissues of tilapia.


Subject(s)
Chlorpyrifos , Tilapia , Water Pollutants, Chemical , Animals , Catalase/metabolism , Chlorpyrifos/metabolism , Chlorpyrifos/toxicity , Ecosystem , Gills/metabolism , Glutathione Transferase/metabolism , Liver/metabolism , Oxidative Stress , Superoxide Dismutase/metabolism , Tilapia/metabolism , Water Pollutants, Chemical/metabolism , Water Pollutants, Chemical/toxicity
15.
Sci Total Environ ; 738: 140317, 2020 Oct 10.
Article in English | MEDLINE | ID: mdl-32806371

ABSTRACT

The chemical mixtures in various environmental media not only have concentration diversity but also mixture-ratio diversity. It is impossible to experimentally determine the toxicities of all mixtures; therefore, it is necessary to develop effective methods based on models to predict mixture toxicity. In this study, a new approach (BNNmix) based on the back-propagation neural network (BPNN) was developed and used to predict the toxicities of seven-component mixtures (consisting of two substituted phenols, two pesticides, two ionic liquids, and one heavy metal) on Caenorhabditis elegans. We found that the combined toxicities of various mixtures used in the experiments were neither global concentration-additive nor global response-additive, which implied that it was impossible to accurately predict the toxicities of such mixtures by using common models such as concentration addition (CA) and response addition (independent action, IA). Using the BNNmix approach to estimate or predict the toxicities of the mixtures under test, it was found that the predictive toxicities of various mixtures with different mixture ratios and concentrations were almost in accordance with those observed experimentally. Unlike the CA and IA models, the BNNmix approach can predict not only the toxicities of mixtures having toxicological interactions but also those with global concentration or response additivities.


Subject(s)
Ionic Liquids , Metals, Heavy , Pesticides , Neural Networks, Computer , Phenols
16.
Eur J Med Chem ; 203: 112589, 2020 Oct 01.
Article in English | MEDLINE | ID: mdl-32717530

ABSTRACT

Aurora Kinase B is a serine-threonine kinase known to be overexpressed in several cancers, with no inhibitors approved for clinical use. Herein, we present the discovery and optimization of a series of novel quinazoline-based Aurora Kinase B inhibitors. The lead inhibitor SP-96 shows sub-nanomolar potency in Aurora B enzymatic assays (IC50 = 0.316 ± 0.031 nM). We identified the important pharmacophore features resulting in selectivity against receptor tyrosine kinases. Particularly, SP-96 shows >2000 fold selectivity against FLT3 and KIT which is important for normal hematopoiesis. This could diminish the adverse effect of neutropenia reported in the clinical trials of the Aurora B inhibitor Barasertib, which inhibits FLT3 and KIT in addition to Aurora B. Enzyme kinetics of SP-96 shows non-ATP-competitive inhibition which makes it a first-in-class inhibitor. Further, SP-96 shows selective growth inhibition in NCI60 screening, including inhibition of MDA-MD-468, a Triple Negative Breast Cancer cell line.


Subject(s)
Adenosine Triphosphate/metabolism , Aurora Kinase B/antagonists & inhibitors , Bone Marrow/drug effects , Drug Design , Protein Kinase Inhibitors/pharmacology , Quinazolines/pharmacology , Binding, Competitive , Bone Marrow/immunology , Cell Line, Tumor , Clinical Trials as Topic , Hematopoiesis/drug effects , Humans , Protein Kinase Inhibitors/adverse effects , Protein Kinase Inhibitors/chemistry , Protein Kinase Inhibitors/metabolism , Quinazolines/adverse effects , Quinazolines/chemistry , Quinazolines/metabolism , Structure-Activity Relationship
17.
Saudi Pharm J ; 28(6): 692-697, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32550800

ABSTRACT

BACKGROUND: Tabernaemontana alternifolia root is traditionally used and practiced among few Indian tribes as an antidote for snakebites. OBJECTIVE: To combat and neutralize Naja naja venom using methanolic root extract of Tabernaemontana alternifolia and to explore its efficacy on venom biomarkers in search of newer herbal antidote or first-aid-point of care for therapeutics.Materialization.Pharmacological activities such as fibrinogenolytic, direct and indirect hemolytic activities for the neutralization of the venom were evaluated. Lethal toxicity annulation studies were performed using the murine model by pre-incubation and post-treatment protocols. Further, the neutralization of edema and myotoxicity were also evaluated. RESULTS: Electrophoretic analysis revealed that the complete neutralization of fibrinogen degradation was observed at 1:10 (w/w) (venom to extract). T. alternifolia exhibited an effective dose (ED50) value of 87.20 µg/mL for venom-induced hemolysis. Venom at 2 µg concentration produced 11 mm of hemolytic radiance and was neutralized at 1:20 (w/w) venom to extract concentration. The survival time and the neurotoxic symptoms in mice were concluded to be delayed by both the methods of lethal toxicity inhibition using methanol extract. The edema ratio reduced the venom to extract ratio of 1:20 (w/w) from 173 ± 45% to 133.61% when subjected to 5 µg of venom concentration. The plant extract significantly neutralized the myotoxic activity. CONCLUSION: T. alternifolia methanolic root extract could be a potent contributor in the effective treatment of N. naja venom-induced toxicity.

18.
Chemosphere ; 257: 127240, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32516670

ABSTRACT

Exaiptasia pallida has been applied as a cnidarian model to assess the toxicity of various contaminants using endpoints related to growth, reproduction and mortality. However, increasingly accepted behavioural and biochemical endpoints are underrepresented in ecotoxicity testing with cnidarian species. The aim of this study was to assess the suitability of tentacle retraction and superoxide dismutase activity as behavioural and biochemical endpoints for ecotoxicity testing with E. pallida. A concentration-dependent, tentacle retraction response was found in sub-lethal toxicity testing for anemones exposed to 1-65 µg L-1 Cu and 2-630 µg L-1 Zn for 24 and 96 h. Semi-quantitative and quantitative approaches to tentacle retraction analysis showed a difference in response sensitivity, however, both methods resulted in similar 24- and 96-h EC50 values for Cu and Zn. Additionally, tentacle retraction analysis provided the benefit of identifying recovery in anemones previously exposed to 359 µg L-1 Zn following a 96-h recovery period. Conversely, no significant difference in superoxide dismutase activity was detected in anemones exposed to the Cu and Zn solutions compared with controls, after either 24- or 96-h exposures. These findings support the ease of application and sensitivity of tentacle retraction as an endpoint in ecotoxicity testing with E. pallida and recommend its suitability for use in acute, sub-lethal toxicity testing. Moreover, evidence of recovery in E. pallida following exposure suggests that recovery should be incorporated into future toxicity assessments.


Subject(s)
Sea Anemones/physiology , Toxicity Tests, Acute , Water Pollutants, Chemical/toxicity , Animals , Copper/toxicity , Sea Anemones/growth & development
19.
Mar Pollut Bull ; 150: 110660, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31727317

ABSTRACT

Growing evidences revealed the deleterious impacts of microplastics (MPs) on marine organisms. However, the effects of MPs on the movement behavior of marine crustacean is poorly understood. Therefore, this study aims to evaluate the physiological and behavioral responses of mysid shrimp (Neomysis japonica) larvae to polystyrene (PS) and carboxylated polystyrene (PS-COOH). PS-COOH presented a greater physiological toxicity to shrimp larvae compared to PS, causing significant lethal and growth inhibition effect, owing to bioaccumulation of MPs inside stomach. Both two MPs decreased the feeding efficiency of larvae, showing weakened predation competence. Moreover, reduced hunting and/or explorative ability of shrimps caused by MPs was also identified, which was evidenced by an overall decrease in swimming activity, range and frequency after exposure. Our study firstly highlighted that micron-sized polystyrene particles had the negative effects on the movement behavior of mysid shrimp larvae, thus posing potential hazard to population dynamics and ecological function of marine crustacean.


Subject(s)
Behavior, Animal/drug effects , Crustacea/physiology , Microplastics/toxicity , Polystyrenes/toxicity , Water Pollutants, Chemical/toxicity , Animals , Plastics , Swimming
20.
Aquat Toxicol ; 216: 105292, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31546069

ABSTRACT

Fipronil is a phenylpyrazole insecticide that entered the market to replace organochlorides and organophosphates. Fipronil impairs the regular inhibition of nerve impulses that ultimately result in paralysis and death of insects. Because of its use as a pest control, and due to runoff events, fipronil has been detected in freshwater systems near agricultural areas, and therefore might represent a threat to non-target aquatic organisms. In this study, the toxicity of fipronil to the freshwater midge Chironomus riparius was investigated at biochemical, molecular, and whole organism (e.g. growth, emergence, and behavior) levels. At the individual level, chronic (28 days) exposure to fipronil resulted in reduced larval growth and emergence with a lowest observed effect concentration (LOEC) of 0.081 µg L-1. Adult weight, which is directly linked to the flying performance and fecundity of midges, was also affected (LOEC = 0.040 µg L-1). Additionally, behavioral changes such as irregular burrowing behavior of C. riparius larvae (EC50 = 0.084 µg L-1) and impairment of adult flying performance were observed. At a biochemical level, acute (48 h) exposure to fipronil increased cellular oxygen consumption (as indicated by the increase of electron transport system (ETS) activity) and decreased antioxidant and detoxification defenses (as suggested by the decrease in catalase (CAT) and glutathione S-transferase (GST) activities). Exposure to fipronil also caused alterations in the fatty acid profile of C. riparius, since high levels of stearidonic acid (SDA) were observed. A comparison between exposed and non-exposed larvae also revealed alterations in the expression of globins, cytoskeleton and motor proteins, and proteins involved in protein biosynthesis. These alterations may aid in the interpretation of potential mechanisms of action that lead to the effects observed at the organism level. Present results show that environmentally relevant concentrations of fipronil are toxic to chironomid populations which call for monitoring of phenylpyrazole insecticides and of their ecological effects in freshwaters. Present results also emphasize the importance of complementing ecotoxicological data with molecular approaches such as proteomics, for a better interpretation of the mode of action of insecticides in aquatic invertebrates.


Subject(s)
Chironomidae/genetics , Fresh Water , Pyrazoles/toxicity , Animals , Biomarkers/metabolism , Chironomidae/drug effects , Chironomidae/growth & development , Female , Geologic Sediments/chemistry , Insecticides/toxicity , Larva/drug effects , Larva/growth & development , Male , Water Pollutants, Chemical/toxicity
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