RESUMEN
The agricultural fumigant pesticide aluminum phosphide (AlP) is cardiotoxic. Water causes AlP to emit phosphine gas, a cardiac toxin that affects heart function and causes cardiogenic shock. AlP poisoning's high fatality rate is due to cardiotoxicity. This study examines how resveratrol reduces oxidative stress, mitochondrial activity, and apoptosis in human cardiac myocyte (HCM) cells. After determining the optimal doses of resveratrol using the MTT test, HCM cells were subjected to a 24-h treatment of resveratrol following exposure to AlP (2.36 µM). The levels of reactive oxygen species (ROS), superoxide dismutase (SOD) activity, mitochondrial swelling, mitochondrial cytochrome c release, and mitochondrial membrane potential (MMP) in HCM cells were investigated. Also, the expression of Bax and Bcl-2, caspace-3 activity, and apoptosis were assessed. The present investigation revealed that AlP substantially increased the level of ROS and decreased SOD activation, which were significantly modulated by resveratrol in a dose-dependent manner. Moreover, AlP induced an elevation of mitochondrial swelling, cytochrome c release, and MMP collapse. Co-administration of resveratrol significantly reduced above mitochondrial markers. AlP also significantly upregulated BAX and downregulated Bcl-2 expression, elevated caspace-3 activity, and apoptosis. Resveratrol co-administration was able to meaningfully modulate the mentioned parameters and finally reduce apoptosis. In conclusion, resveratrol, via its pleotropic properties, significantly demonstrated cytoprotective effects on HCM cytotoxicity induced by AlP.
Asunto(s)
Compuestos de Aluminio , Apoptosis , Cardiotoxicidad , Potencial de la Membrana Mitocondrial , Miocitos Cardíacos , Estrés Oxidativo , Plaguicidas , Fosfinas , Especies Reactivas de Oxígeno , Resveratrol , Fosfinas/toxicidad , Compuestos de Aluminio/toxicidad , Resveratrol/farmacología , Apoptosis/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Humanos , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/patología , Miocitos Cardíacos/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Plaguicidas/toxicidad , Antioxidantes/farmacología , Mitocondrias Cardíacas/efectos de los fármacos , Mitocondrias Cardíacas/metabolismo , Mitocondrias Cardíacas/patología , Línea Celular , Relación Dosis-Respuesta a DrogaRESUMEN
BACKGROUND: During the last decade, the evaluation of certain behavioral attributes has been utilized as an indicator of resistance to phosphine. In this context, an underappreciated challenge may be the development of behavioral traits that are related with resistance to phosphine such as the movement to refugia and recovery of stored product insects after short exposures. Thus, the aim of the current study was to track the movement of phosphine-resistant and -susceptible adults of the red flour beetle, Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae), which is a major pest of stored products, after brief exposures to phosphine. Exposures were followed for extended intervals to assess the recovery patterns and how those patterns are related to known resistance to phosphine. A video-tracking procedure coupled with Ethovision software was used to assess movement after exposure. RESULTS: Overall, we found baseline movement was less for phosphine-resistant T. castaneum, suggesting resistance comes at a considerable fitness cost. In the presence of phosphine (1000 or 3000 ppm), there was a much greater reduction in movement for phosphine-susceptible than phosphine-resistant T. castaneum adults immediately after brief 5-min exposures. Twenty-four hours later, these effects were more variable and less apparent, regardless of the susceptibility level. CONCLUSIONS: The initial knockdown associated with successful fumigation may just be a temporary state whereafter insects shortly resume movement and may be able to seek out refugia from phosphine, thereby promoting the development of resistance. Our results strengthen a growing consensus that it is the speed to knockdown that truly matters, with quick knockdown indicating slow recovery and a reduced likelihood for the occurrence of resistance. © 2023 Society of Chemical Industry. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
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Insecticidas , Fosfinas , Tribolium , Animales , Escarabajos , Resistencia a los Insecticidas , Insecticidas/toxicidad , Fosfinas/toxicidadRESUMEN
Phosphine (PH3) is an ideal fumigant alternative on methyl bromide (MB) as MB has been classified as an ozone-depleting substance. However, several challenges limit its efficient use in crop production, including the emergence of PH3-resistant insect pests and the incidence of phytotoxic effects on nursery plants. Therefore, this study aims to elucidate the mechanism underlying PH3 phytotoxicity in plants using transcriptomic techniques. Fumigation with 2 g/m3 PH3 induced phytotoxic effects in A. thaliana, as evidenced by a decrease in growth and vegetation indices compared to the control group. Transcriptomic analysis revealed that PH3 fumigation phytotoxicity responses in A. thaliana involve genes related to hypoxia stress and energy metabolism. Additionally, pretreatment with ethylene induced pre-adaptation to hypoxia under light conditions during fumigation effectively suppressed the phytotoxic effects of PH3 in A. thaliana by increasing the expression of hypoxia-adaptive genes. Moreover, the phytotoxicity of PH3 was also confirmed in pumpkin (Cucurbita moschata Duch.), and was dependent on light. Overall, our findings showed that fumigation under light conditions and ethylene pretreatment could be used to minimize PH3-induced phytotoxic effects in plants.
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Arabidopsis , Cucurbita , Fosfinas , Arabidopsis/genética , Transcriptoma , Fosfinas/toxicidad , Hipoxia , Metabolismo Energético , EtilenosRESUMEN
Environmental monitoring data have indicated that three chlorinated organophosphorus flame retardants (Cl-OPFRs), including tris(2-chloroethyl)-phosphate (TCEP), tris(2-chloropropyl)-phosphate (TCPP), and tris(1,3-dichloro-2-propyl)-phosphate (TDCPP) are the predominant chemicals in various environmental matrices and exhibit reproductive endocrine disrupting activities. Currently, mitochondrial abnormality is a new paradigm for evaluating chemical-mediated cell dysfunction. However, a comprehensive correlation between these two aspects of Cl-OPFRs remains unclear. In this research, the effects of TCEP, TCPP, and TDCPP on progesterone production and mitochondrial impairment were investigated by using mouse Leydig tumor cells (mLTC-1). The half maximal inhibitory concentration (IC50) values at 48 h exposure indicated that the rank order of anti-androgenic activity was TDCPP > TCPP. Whereas, TCEP exhibited elevation of progesterone production. At concentrations close to IC50 of progesterone production by TCPP and TDCPP, the elevation of intracellular reactive oxygen species (ROS), depletion of mitochondrial membrane potential (MMP), reduction of cellular adenosine triphosphate (ATP) content, and alteration of mitochondrial structures was observed. In addition, the expression of main genes related to progesterone synthesis was dramatically down-regulated by TCPP and TDCPP treatments. These results imply that the inhibition effect of TCPP and TDCPP on progesterone production might be related to mitochondrial damage and down-regulated steroidogenic genes.
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Monitoreo del Ambiente , Retardadores de Llama , Mitocondrias , Organofosfatos , Fosfinas , Progesterona , Animales , Ratones , Adenosina Trifosfato/metabolismo , Retardadores de Llama/toxicidad , Organofosfatos/toxicidad , Fosfinas/toxicidad , Progesterona/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Tumor de Células de Leydig , Mitocondrias/efectos de los fármacos , Mitocondrias/patología , Monitoreo del Ambiente/métodosRESUMEN
Aluminum phosphide (AlP) poisoning is common in many countries responsible for high mortality. The heart is the main target organ in AlP poisoning. Several studies have reported the beneficial effects of cannabidiol (CBD) in reducing heart injuries. This study aimed to investigate the possible protective effect of CBD on cardiac toxicity caused by AlP poisoning. Study groups included almond oil, normal saline, sole CBD (100 µg/kg), AlP (11.5 mg/kg), and four groups of AlP + CBD (following AlP gavage, CBD administrated at doses of 5, 25, 50, and 100 µg/kg via intravenous (iv) injection). Thirty minutes after AlP treatment, an electronic cardiovascular device (PowerLab) was used to record electrocardiographic (ECG) changes, heart rate (HR), and blood pressure (BP) for three hours. Cardiac tissue was examined for the activities of mitochondrial complexes, ADP/ATP ratio, the release of cytochrome C, mitochondrial membrane potential (MMP), apoptosis, oxidative stress parameter, and cardiac biomarkers at 12 and 24 hours time points. AlP administration caused abnormal ECG, decreased HR, and BP. AlP also significantly reduced mitochondrial complex I and IV activity and ADP/ATP ratio. The level of cytochrome C release, apoptosis, oxidative stress, and cardiac biomarkers was considerably increased by AlP, which was compensated following CBD administration. CBD was able to improve hemodynamic function to some extent in AlP poisoned rats. CBD restored ATP levels and mitochondrial function and decreased oxidative damage and thus, prevented the heart cells from entering the apoptotic stage. Further clinical trials are needed to explore any possible benefits of CBD in AlP-poisoned patients.
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Cannabidiol , Fosfinas , Animales , Cannabidiol/toxicidad , Electrocardiografía , Frecuencia Cardíaca , Humanos , Mitocondrias , Fosfinas/toxicidad , Ratas , Ratas WistarRESUMEN
The aim is to assess the prevalence and knowledge on acute occupational exposure to phosphine in the shipping industry. We followed PRISMA guidelines for scoping review. We searched in 4 databases without language and date restrictions for scientific articles in peer-reviewed and gray literature. We found 13 peer-reviewed articles and 63 articles in gray literature. These covered 56 incidents from 1963 to 2019 for a total of 254 victims and 22 fatalities. There is an increase in the number of reported cases over the last 20 years. Neurologic and gastrointestinal symptoms are predominant, and hospitalization is needed in 80% of cases. Our review underlined the principal risk as gas exposure through leaks between holds and the ventilation system. Further studies on the knowledge and the prevention in order to improve good practices onboard, prevent the risk of fire explosion, and a global reporting system of new cases are recommended.
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Medicina Naval , Exposición Profesional , Fosfinas/envenenamiento , Fosfinas/toxicidad , NavíosRESUMEN
Aluminum phosphide (AlP) poisoning can be deadly in most cases targeting the heart. To overcome AlP toxicity, exenatide has been studied in the present study due to its pleiotropic effects on cardiac damages. In this study, the rats were exposed to LD50 of AlP (10 mg/kg) by gavage, and exenatide at doses (0.05, 0.1, and 0.2 mg/kg) injected intraperitoneally 30 min after poisoning. The cardiac parameters including heart rate (HR), blood pressure (BP), QRS, corrected QT (QTc), and ST were monitored for 180 min. Blood glucose level was measured in the study groups 30 min after exenatide injection. Evaluation of biochemical parameters including mitochondrial complexes I, II, and IV activities, adenosine diphosphate (ADP)/adenosine triphosphate (ATP) ratio, malondialdehyde (MDA), apoptosis, lactate, troponin I, and brain natriuretic peptide (BNP) was done on heart tissues after 12 and 24 h. Additionally, the tissues were analyzed for any pathological damages including necrosis, hemorrhage, or hyperemia 24 h post-treatment. Our results showed that AlP-induced HR, BP, and electrocardiographic changes were improved by exenatide at all doses. The blood glucose levels of poisoned animals reached control levels after exenatide treatment. Besides, treatment with exenatide at all doses improved complexes I and IV activity, ADP/ATP ratio, and apoptosis. Malondialdehyde, lactate, troponin I, and BNP levels were also diminished after exenatide co-treatment in poisoned animals. On the other hand, administration of exenatide doses improved the histopathology of AlP-induced tissues. Based on our findings, exenatide has a protective effect against phosphine-induced cardiotoxicity in an almost dose-dependent way. However, further investigations are needed on the potential clinical use of exenatide in this poisoning.
Asunto(s)
Compuestos de Aluminio/toxicidad , Presión Sanguínea/efectos de los fármacos , Electrocardiografía , Exenatida/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Incretinas/farmacología , Fosfinas/toxicidad , Animales , Glucemia/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Exenatida/administración & dosificación , Dosificación Letal Mediana , Peroxidación de Lípido , Masculino , Distribución Aleatoria , Ratas , Ratas WistarRESUMEN
Phosphine (PH3) is a highly toxic, corrosive, flammable, heavier-than-air gas that is a commonly used fumigant. When used as a fumigant, PH3 can be released from compressed gas tanks or produced from commercially available metal phosphide tablets. Although the mechanism of toxicity is unclear, PH3 is thought to be a metabolic poison. PH3 exposure induces multiorgan toxicity, and no effective antidotes or therapeutics have been identified. Current medical treatment consists largely of supportive care and maintenance of cardiovascular function. To better characterize the mechanism(s) driving PH3-induced toxicity, we have performed transcriptomic analysis on conscious adult male Sprague-Dawley rats following whole-body inhalation exposure to phosphine gas at various concentration-time products. PH3 exposure induced concentration- and time-dependent changes in gene expression across multiple tissues. These gene expression changes were mapped to pathophysiological responses using molecular pathway analysis. Toxicity pathways indicative of cardiac dysfunction, cardiac arteriopathy, and cardiac enlargement were identified. These cardiotoxic responses were linked to apelin-mediated cardiomyocyte and cardiac fibroblast signaling pathways. Evaluation of gene expression changes in blood revealed alterations in pathways associated with the uptake, transport, and utilization of iron. Altered erythropoietin signaling was also observed in the blood. Upstream regulator analysis identified several therapeutics predicted to counteract PH3-induced gene expression changes. These include antihypertensive drugs (losartan, candesartan, and prazosin) and therapeutics to reduce pathological cardiac remodeling (curcumin and TIMP3). This transcriptomics study has characterized molecular pathways involved in PH3-induced cardiotoxicity. These data will aid in elucidating a precise mechanism of toxicity for PH3 and guide the development of effective medical countermeasures for PH3-induced toxicity.
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Plaguicidas/toxicidad , Fosfinas/toxicidad , Rodenticidas/toxicidad , Transcriptoma/efectos de los fármacos , Administración por Inhalación , Animales , Antihipertensivos/farmacología , Apelina/metabolismo , Cardiomegalia/inducido químicamente , Cardiotónicos/farmacología , Cardiotoxicidad/genética , Cardiotoxicidad/metabolismo , Corazón/efectos de los fármacos , Masculino , Fosfinas/administración & dosificación , Ratas Sprague-Dawley , Rodenticidas/administración & dosificación , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND: Aluminum phosphide (AlP) causes severe cardiotoxicity. Taurine has been chosen for the present study because of its positive known effects on cardiac injuries. METHOD: To evaluate AlP-induced cardiotoxicity, the animals were divided into seven groups, including the control group, the taurine group (500 mg/kg), AlP with LD50 dose, AlP + taurine 20, 50, 100, and 200 mg/kg group. To assess cardiac hemodynamic parameters, Wistar rats received taurine intraperitoneally 60 min after AlP gavage. Cardiac hemodynamic parameters were evaluated for 180 min. To study biochemical parameters, 24 h after AlP treatment, the animals were sacrificed, and heart tissues were collected. RESULT: ECG, BP, and HR abnormalities of AlP poisoning were improved by taurine treatment. AlP induced biochemical alterations including complexes I and IV activities, the ADP/ATP ratio, mitochondrial membrane potential, cytochrome C release, and oxidative stress biomarkers ameliorated by taurine. Moreover, taurine improved apoptosis, as well as lessened CK-MB and troponin I levels. Also, there were no significant changes between taurine 500 mg/kg and the control group in tests. CONCLUSION: The present findings showed that taurine could be a possible candidate for AlP cardiotoxicity treatment via the effect on mitochondrial electron transfer chain and maintaining intracellular ATP balance.
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Compuestos de Aluminio/toxicidad , Cardiotónicos/uso terapéutico , Cardiotoxicidad/tratamiento farmacológico , Fosfinas/toxicidad , Taurina/uso terapéutico , Animales , Presión Sanguínea/efectos de los fármacos , Cardiotoxicidad/metabolismo , Creatina Quinasa/metabolismo , Electrocardiografía/efectos de los fármacos , Proteínas del Complejo de Cadena de Transporte de Electrón/metabolismo , Corazón/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Masculino , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Mitocondrias/enzimología , Miocardio/enzimología , Estrés Oxidativo/efectos de los fármacos , Ratas Wistar , Troponina I/metabolismoRESUMEN
The use of natural products as potential ligands has been explored as a strategy in the development of metal-based chemotherapy. Since ruthenium complexes are promising alternatives to traditional antitumor agents, this study evaluated the anti-melanoma potential of two ruthenium(II) complexes containing the naphthoquinone ligands lapachol (lap), [Ru(lap)(dppm)2]PF6, and lawsone (law), [Ru(law)(dppm)2]PF6, in addition to the bis(diphenylphosphino)methane (dppm) ligand, referred to as complexes (1) and (2), respectively, using a syngeneic murine melanoma model. Activation of the apoptotic pathway by the treatments was assessed by immunohistochemistry in tumor tissue. Additionally, toxicity of the treatments was evaluated by variation in body and organ weight, quantification of biochemical indicators of renal damage, and genotoxicity in bone marrow and hepatocytes. First, the antiproliferative activity of (1) and (2) was observed in B16F10 cells, with IC50 values of 2.78 and 1.68 µM, respectively. The results obtained in mice showed that, unlike complex (1), (2) possesses significant anti-melanoma activity demonstrated by a reduction in tumor volume and mass (88.42%), as well as in mitosis frequency (83.86%). Additionally, complex (2) increased the levels of cleaved caspase-3, inducing tumor cell apoptosis. When compared to the metallodrug cisplatin, complex (2) exhibited similar anti-melanoma activity and lower toxicity considering all parameters evaluated. In silico studies demonstrated no difference in the binding energy of the naphthoquinone complex between complexes (1) and (2). However, the complex containing the lawsone ligand has a lower molar volume, which may be important for interactions with minor DNA grooves. The present results demonstrate the antitumor efficiency of complex (2) and a significantly lower systemic toxicity compared to cisplatin.
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Antineoplásicos/uso terapéutico , Complejos de Coordinación/uso terapéutico , Melanoma/tratamiento farmacológico , Naftoquinonas/uso terapéutico , Fosfinas/uso terapéutico , Animales , Antineoplásicos/toxicidad , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Complejos de Coordinación/toxicidad , Ligandos , Masculino , Ratones Endogámicos C57BL , Naftoquinonas/toxicidad , Fosfinas/toxicidad , Rutenio/química , Rutenio/toxicidadRESUMEN
The primary focus of our research was to obtain global gene expression data in baker's yeast exposed to sub-lethal doses of quantum dots (QDs), such as green-emitting CdSe/ZnS and InP/ZnS, to reveal novel insights on their unique mechanisms of toxicity. Despite their promising applications, their toxicity and long-lasting effects on the environment are not well understood. To assess toxicity, we conducted cell viability assays, ROS detection assays, and assessed their effects on the trafficking of Vps10-GFP toward the trans-Golgi network with confocal microscopy. Most notably, we used RNA-sequencing (RNA-seq) to obtain gene expression profiles and gene identities of differentially expressed genes (DEGs) in QD-treated yeast. We found CdSe/ZnS QDs significantly altered genes implicated in carboxylic acid, amino acid, nitrogen compounds, protein metabolic processes, transmembrane transport, cellular homeostasis, cell wall organization, translation, and ribosomal biogenesis. Additionally, we found InP/ZnS QDs to alter genes associated with oxidation-reduction, transmembrane transport, metal ion homeostasis, cellular component organization, translation, and protein and nitrogen compound metabolic processes. Interestingly, we observed an increase in reactive oxygen species (ROS) in CdSe/ZnS-treated cells and a decrease in ROS levels in InP/ZnS-treated cells. Nevertheless, we concluded that both QDs modestly contributed cytotoxic effects on the budding yeast.
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Perfilación de la Expresión Génica/métodos , Puntos Cuánticos/toxicidad , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/crecimiento & desarrollo , Compuestos de Cadmio/toxicidad , Regulación Fúngica de la Expresión Génica/efectos de los fármacos , Indio/toxicidad , Viabilidad Microbiana/efectos de los fármacos , Fosfinas/toxicidad , Especies Reactivas de Oxígeno/metabolismo , Saccharomyces cerevisiae/efectos de los fármacos , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Compuestos de Selenio/toxicidad , Análisis de Secuencia de ARN , Sulfuros/toxicidad , Compuestos de Zinc/toxicidadRESUMEN
OBJECTIVES: The effects of Crocin as a cardioprotective material against Aluminum phosphide poisoning by reducing the oxidative stress is investigated. METHODS: The level of biomarkers of oxidative stress (Catalase, Superoxide dismutase, Malondialdehyde and Protein carbonyl) were measured in the cell culture model on Human Cardiac Myocyte cells to detect the protective effect of crocin. Initially, to define the pure impact of aluminum phosphide poison and crocin on the heart cells, their effects on the biomarkers quantity in cell line were measured, separately, using the standard related kits. Later the effect of crocin with different concentration as a treatment on the oxidative stress biomarkers of the poisoned heart cells were monitored. Note that in pre-treatment case, the crocin was initially added to the cells before poisoning them. Data were analyzed using the analysis of variance method. KEY FINDINGS: Results showed that crocin treatment reduced the aluminum phosphide (AlP) poisoning effect significantly. The treatment resulted in substantial deviation in the biomarkers of oxidative stress at the pre- and post-treatment phases for all groups. The oxidative markers values of the poisoned cells were recovered by crocin treatment. CONCLUSIONS: Crocin is proposed as a potentially powerful antioxidant to treat the cardiotoxicity caused by aluminum phosphide poisoning.
Asunto(s)
Compuestos de Aluminio/toxicidad , Antioxidantes/farmacología , Carotenoides/uso terapéutico , Crocus/química , Miocardio/metabolismo , Miocitos Cardíacos/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Fosfinas/toxicidad , Antídotos/farmacología , Antídotos/uso terapéutico , Antioxidantes/metabolismo , Antioxidantes/uso terapéutico , Biomarcadores/metabolismo , Cardiotoxicidad , Carotenoides/farmacología , Catalasa/metabolismo , Corazón/efectos de los fármacos , Humanos , Malondialdehído/metabolismo , Miocardio/citología , Miocitos Cardíacos/metabolismo , Plaguicidas/toxicidad , Fitoterapia , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Carbonilación Proteica , Superóxido Dismutasa/metabolismoRESUMEN
Ruthenium(II) complexes are currently considered attractive alternatives to the widely used platinum-based drugs. We present herein the synthesis and characterization of half-sandwich ruthenium compounds formulated as [Ru(p-cymene)(L)Cl][CF3SO3] (L = 1,1-bis(methylenediphenylphosphano)ethylene, 1; L = 1,1-bis(diphenylphosphano)ethylene, 2), which were characterized by elemental analysis, mass spectrometry, 1H and 31P{1H} NMR, UV-vis and IR spectroscopy, conductivity measurements and cyclic voltammetry. The molecular structures for both complexes were determined by single-crystal X-ray diffraction. Their cytotoxic activity was evaluated using the MTT assay against human tumor cells, namely ovarian (A2780) and breast (MCF7 and MDA-MB-231). Both complexes were active against breast adenocarcinoma cells, with complex 1 exhibiting a quite remarkable cytotoxicity in the submicromolar range. Interestingly, at concentrations equivalent to the IC50 values in the MCF7 cancer cells, complexes 1 and 2 presented lower cytotoxicity in normal human primary fibroblasts. The antiproliferative effects of 1 and 2 in MCF7 cells might be associated with the induction of reactive oxygen species (ROS), leading to a combined cell death mechanism via apoptosis and autophagy. Despite the fact that in vitro a partial intercalation between complexes and DNA was observed, no MCF7 cell cycle delay or arrest was observed, indicating that DNA might not be a direct target. Complexes 1 and 2 both exhibited a moderate to strong interaction with human serum albumin, suggesting that protein targets may be involved in their mode of action. Their acute toxicity was evaluated in the zebrafish model. Complex 1 (the most toxic of the two) exhibited a lethal toxicity LC50 value about 1 order of magnitude higher than any IC50 concentrations found for the cancer cell models used, highlighting its therapeutic relevance as a drug candidate in cancer chemotherapy.
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Antineoplásicos/farmacología , Complejos de Coordinación/farmacología , Fosfinas/farmacología , Animales , Antineoplásicos/síntesis química , Antineoplásicos/metabolismo , Antineoplásicos/toxicidad , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Complejos de Coordinación/síntesis química , Complejos de Coordinación/metabolismo , Complejos de Coordinación/toxicidad , ADN/metabolismo , Ensayos de Selección de Medicamentos Antitumorales , Fibroblastos/efectos de los fármacos , Humanos , Fosfinas/síntesis química , Fosfinas/metabolismo , Fosfinas/toxicidad , Unión Proteica , Especies Reactivas de Oxígeno/metabolismo , Rutenio/química , Albúmina Sérica Humana/metabolismo , Pez CebraRESUMEN
Photoinitiators (PIs) are widely used for photopolymerization in industrial area and recently paid close attention to in biomedical field. However, there are few reports on their toxicity to human health. Here we explored cytotoxicity and cytocompatibilty of seven commercial and industrial-used PIs for developing their potential clinical application. Phenylbis(acyl) phosphine oxides (BAPO), 2-Benzyl-2-(dimethylamino)-4'-morpholinobutyrophenone (369), 4,4'-Bis(diethylamino) benzophenone (EMK), Diphenyl (2,4,6-trimethylbenzoyl) phosphine oxide (TPO), and 2-Isopropylthioxanthone (ITX) caused different extent cytotoxicities to four tissue types of cells at the concentrations of 1 to 50 µM under a non-irradiation condition, of which the BAPO cytotoxicity was the highest, whereas Ethyl (2,4,6-trimethylbenzoyl) phenylphosphinate (TPOL) and Methyl benzoylformate (MBF) displayed the lowest cellular toxicity. The cell lines and primary cells appeared highly sensitive to BAPO toxicity, the primary lymphocytes relatively to photoinitiator 369 (369) and EMK toxicities, LO2 cells to EMK and TPO toxicities, the primary lymphocytes and HUVEC-12 cells to MBF toxicity, but only HEK293T cells not to 369 toxicity. Furthermore, these PIs led to increasing cytotoxicity to different extents after exposure to 455 nm blue light, which is consistent with non-irradiation tendency. All the cells presented low sensitivity to TPOL and MBF, of which TPOL-triggered polymer is dramatically superior in its cytocompatibility to MBF, and in its transparency to clinically exclusively-used camphorquinone (CQ). The novel findings indicate that BAPO is the most toxic among the seven PIs, but TPOL and MBF are the least toxic, directing their development and application. Combined their triggered polymer cytocompatibility and color with reported deep curing efficiency, TPOL is more promising to be applied especially to clinical practice.
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Benzofenonas/toxicidad , Butirofenonas/toxicidad , Óxidos N-Cíclicos/toxicidad , Luz , Fosfinas/toxicidad , Fotoiniciadores Dentales/toxicidad , Polímeros/toxicidad , Tioxantenos/toxicidad , Animales , Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Línea Celular , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Femenino , Humanos , Linfocitos/efectos de los fármacos , Linfocitos/efectos de la radiación , Masculino , Ratones Endogámicos C57BL , PolimerizacionRESUMEN
InP QDs have shown a great potential as cadmium-free QDs alternatives in biomedical applications. It is essential to understand the biological fate and toxicity of InP QDs. In this study, we investigated the in vivo renal toxicity of InP/ZnS QDs terminated with different functional groups-hydroxyl (hQDs), amino (aQDs) and carboxyl (cQDs). After a single intravenous injection into BALB/c mice, blood biochemistry, QDs distribution, histopathology, inflammatory response, oxidative stress and apoptosis genes were evaluated at different predetermined times. The results showed fluorescent signals from QDs could be detected in kidneys during the observation period. No obvious changes were observed in histopathological detection or biochemistry parameters. Inflammatory response and oxidative stress were found in the renal tissues of mice exposed to the three kinds of QDs. A significant increase of KIM-1 expression was observed in hQDs and aQDs groups, suggesting hQDs and aQDs could cause renal involvement. Apoptosis-related genes (Bax, Caspase 3, 7 and 9) were up-regulated in hQDs and aQDs groups. The above results suggested InP/ZnS QDs with different surface chemical properties would cause different biological behaviors and molecular actions in vivo. The surface chemical properties of QDs should be fully considered in the design of InP/ZnS QDs for biomedical applications.
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Indio/química , Indio/toxicidad , Riñón/efectos de los fármacos , Fosfinas/química , Fosfinas/toxicidad , Puntos Cuánticos/química , Puntos Cuánticos/toxicidad , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Dióxido de Carbono/química , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Radical Hidroxilo/química , Indio/administración & dosificación , Indio/farmacocinética , Inflamación/inducido químicamente , Inyecciones Intravenosas , Riñón/metabolismo , Ratones , Ratones Endogámicos BALB C , Estrés Oxidativo/efectos de los fármacos , Fosfinas/administración & dosificación , Fosfinas/farmacocinética , Puntos Cuánticos/administración & dosificación , Sulfuros/administración & dosificación , Sulfuros/química , Sulfuros/farmacocinética , Sulfuros/toxicidad , Propiedades de Superficie , Distribución Tisular , Compuestos de Zinc/administración & dosificación , Compuestos de Zinc/química , Compuestos de Zinc/farmacocinética , Compuestos de Zinc/toxicidadRESUMEN
Nowadays, poisoning with metal phosphides, especially aluminum phosphide (ALP), is one of the main health threats in human societies. Patients suffer from significant complications due to this type of poisoning, and the heart is one of the main organs targeted by ALP. Therefore, in this study, we discussed the effect of phosphine on cardiac function. This study is based on data obtained from PubMed, between 2002 and 2020. The key keywords included "Aluminum phosphide," "Oxidative Stress," "Mitochondria," "Cardiovascular disease," and "Treatment." The results showed that ALP produced reactive oxygen species (ROS) due to mitochondrial dysfunction. ROS production leads to red blood cell hemolysis, decreased ATP production, and induction of apoptosis in cardiomyocytes, which eventually results in cardiovascular disease. Since ALP has the most significant effect on cardiomyocytes, the use of appropriate treatment strategies to restore cell function can increase patients' survival.
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Compuestos de Aluminio/toxicidad , Enfermedades Cardiovasculares/inducido químicamente , Mitocondrias Cardíacas/efectos de los fármacos , Miocitos Cardíacos/efectos de los fármacos , Plaguicidas/toxicidad , Fosfinas/toxicidad , Animales , Apoptosis/efectos de los fármacos , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/fisiopatología , Metabolismo Energético/efectos de los fármacos , Hemólisis/efectos de los fármacos , Humanos , Mitocondrias Cardíacas/metabolismo , Mitocondrias Cardíacas/patología , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Estrés Oxidativo/efectos de los fármacos , Pronóstico , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Indium phosphide/zinc sulfate (InP/ZnS) quantum dots (QDs) are presumed to be less hazardous than those that contain cadmium. However, the toxicological profile has not been established. The present study investigated the acute toxicity of InP/ZnS QDs with different surface modifications (COOH, NH2, and OH) in mice after pulmonary aerosol inhalation. InP/ZnS QDs were able to pass through the blood-gas barrier and enter the circulation, and subsequently accumulated in major organs. No obvious changes were observed in the body weight or major organ coefficients. Red blood cell counts and platelet-related indicators were in the normal range, but the proportion of white blood cells was altered. The InP/ZnS QDs caused varying degrees of changes in some serum markers, but no histopathological abnormalities related to InP/ZnS QDs treatment was observed in major organs except that hyperemia in alveolar septa was found in lung sections. These results suggested that the effects of respiratory exposure to InP/ZnS QDs on the lungs need to be fully considered in future biomedical application although the overall toxicity of quantum dots is relatively low.
Asunto(s)
Pulmón , Puntos Cuánticos , Administración por Inhalación , Animales , Peso Corporal/efectos de los fármacos , Femenino , Indio/administración & dosificación , Indio/farmacocinética , Indio/toxicidad , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/patología , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Pulmón/patología , Ratones , Ratones Endogámicos BALB C , Microscopía Fluorescente , Fosfinas/administración & dosificación , Fosfinas/farmacocinética , Fosfinas/toxicidad , Puntos Cuánticos/administración & dosificación , Puntos Cuánticos/análisis , Puntos Cuánticos/metabolismo , Puntos Cuánticos/toxicidad , Propiedades de Superficie , Distribución Tisular , Sulfato de Zinc/administración & dosificación , Sulfato de Zinc/farmacocinética , Sulfato de Zinc/toxicidadRESUMEN
Apart from the anticancer, antioxidant, anti-inflammatory effects, and inhibition of aromatase, chrysin is involved in the protection of cardiovascular disorders. Cardiovascular complications are the main cause of death induced by aluminum phosphide (AlP) which is related to oxidative stress and mitochondrial damages. For this purpose, we investigated the effect of chrysin as an antioxidant and mitochondrial protective agent against AlP-induced toxicity in isolated cardiomyocytes and mitochondria obtained from rat heart ventricular. Using by biochemical and flow cytometry, cell viability, reactive oxygen species (ROS) formation, mitochondria membrane potential (MMP), lysosomal membrane integrity, malondialdehyde (MDA) content, and glutathione (GSH) and oxidized glutathione (GSSG) content were measured in isolated cardiomyocytes. Also, mitochondrial toxicity parameters such as mitochondrial NADH/succinate dehydrogenase activity, mitochondrial swelling, ROS formation, MMP collapse, and lipid peroxidation were analyzed in isolated mitochondria. Our results showed that the administration of chrysin (up to 10 µM) efficiently decreased (P < 0.05) cytotoxicity, oxidative, lysosomal, and mitochondrial damages induced by AlP, in isolated cardiomyocytes. Also, our finding in isolated mitochondria showed that chrysin (up to 10 µM) significantly (P < 0.05) decreased AlP-induced mitochondrial toxicity. These findings demonstrated that chrysin as an antioxidant and mitochondrial protective agent exert protective effect in wild-type cardiomyocyte treated with AlP. It was concluded that chrysin significantly reduced the toxicity of AlP in isolated cardiomyocytes and mitochondria. Due to the very low toxicity of chrysin for humans, it could be a promising agent in treatment of AlP poisoning.
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Compuestos de Aluminio/toxicidad , Flavonoides/farmacología , Mitocondrias Cardíacas/efectos de los fármacos , Miocitos Cardíacos/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Fosfinas/toxicidad , Sustancias Protectoras/farmacología , Animales , Cardiotoxicidad , Células Cultivadas , Glutatión/metabolismo , Humanos , Peroxidación de Lípido/efectos de los fármacos , Lisosomas/metabolismo , Masculino , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias Cardíacas/metabolismo , Dilatación Mitocondrial/efectos de los fármacos , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismoRESUMEN
As a typical organophosphorus flame retardant, tris (2-chloroethyl) phosphate (TCEP) has been widely detected in various environmental media. Toxicity of TCEP to vertebrates have been investigated, but potential effects on lower trophic level species were unknown to date. In this study, toxic effects and molecular mechanisms of toxic actions of TCEP on the aquatic protozoan Tetrahymena thermophila were evaluated by use of phenotypic observations, transcriptome sequencing analysis and real-time quantitative PCR detection. Exposure to 0.044, 0.411 or 4.26â¯mg/L TCEP for 5 days decreased the theoretical population, cell viability, number of cilia and cell size of Tetrahymena thermophila in a time- and dose-dependent manner. Meanwhile, RNA-Seq analysis indicated that exposure to 4.26â¯mg/L TCEP significantly changed expression of 2932 genes (up-regulation: 1228; down-regulation: 1704). Of these, expressions of 9, 10 and 17 genes that were enriched in soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) interaction in vesicular transport, proteasome and endocytosis pathway respectively were down-regulated. Data collected during this study suggested that exposure to high concentrations of TCEP might affect growth and reproduction of Tetrahymena thermophila through down-regulating transcriptional levels of genes encoding proteins associated with vesicle trafficking, proteasome and endocytosis.
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Retardadores de Llama/toxicidad , Fosfinas/toxicidad , Tetrahymena thermophila/efectos de los fármacos , Transcripción Genética/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Animales , Supervivencia Celular/efectos de los fármacos , Regulación hacia Abajo , Perfilación de la Expresión Génica , Reproducción/efectos de los fármacos , Tetrahymena thermophila/genética , Tetrahymena thermophila/crecimiento & desarrollo , Regulación hacia ArribaRESUMEN
Cobalt phosphate engineered nanomaterials (ENMs) are an important class of materials that are used as lithium ion battery cathodes, catalysts, and potentially as super capacitors. As production of these nanomaterials increases, so does the likelihood of their environmental release; however, to date, there are relatively few investigations of the impact of nanoscale metal phosphates on biological systems. Furthermore, nanomaterials used in commercial applications are often multiphase materials, and analysis of the toxic potential of mixtures of nanomaterials has been rare. In this work, we studied the interactions of two model environmental bacteria, Shewanella oneidensis MR-1 and Bacillus subtilis, with a multiphase lithiated cobalt phosphate (mLCP) nanomaterial. Using a growth-based viability assay, we found that mLCP was toxic to both bacteria used in this study. To understand the observed toxicity, we screened for production of reactive oxygen species (ROS) and release of Co2+ from mLCP using three abiotic fluorophores. We also used Newport Green DCF dye to show that cobalt was taken up by the bacteria after mLCP exposure. Using transmission electron microscopy, we noted that the mLCP was not associated with the bacterial cell surface. In order for us to further probe the mechanism of interaction of mLCP, the bacteria were exposed to an equivalent dose of cobalt ions that dissolved from mLCP, which recapitulated the changes in viability when the bacteria were exposed to mLCP, and it also recapitulated the observed bacterial uptake of cobalt. Taken together, this implicates the release of cobalt ions and their subsequent uptake by the bacteria as the major toxicity mechanism of mLCP. The properties of the ENM govern the release rate of cobalt, but the toxicity does not arise from nanospecific effects-and importantly, the chemical composition of the ENM may dictate the oxidation state of the metal centers and thus limit ROS production.