RESUMEN
Conventional wastewater treatment methods cannot completely remove the ultraviolet (UV) filters or dissolved organic matter. The transformation characteristics of these substances during chlorination disinfection and the varying species-specific toxicities of their combinations remain unclear. Here, Daphnia magna and zebrafish were exposed to benzophenone-3 (BP-3) and humic acid (HA) before and after chlorination disinfection. The results from chemical indicators showed that chlorination treatment decreased UV254 values and changed the intensity of parallel factors in three-dimensional fluorescence. Based on chemical analysis, the chlorine concentration and chlorination time for the toxicity experiments were set at 5 mg/L and 6 h, respectively. Exposure to HA and BP-3 before and after chlorination decreased the heart rate (by 1.37-28.12 %) in both species. However, species-specific responses, including survival rate, swimming distance, and expression of genes related to neurodevelopment, growth, and oxidative stress, were induced by chlorination. Chlorination reduced the impact of HA exposure but worsened the effects of HA and BP-3 co-exposure on D. magna. However, in zebrafish, the toxic effects intensified in most of the exposure groups after chlorination. Correlation analysis showed that the parallel factors of three-dimensional fluorescence were correlated with toxic effects on zebrafish, whereas UV254 was more significantly correlated with toxic effects on D. magna. This study provides insights into the combined toxicity of UV filters and dissolved organic matter in different aquatic organisms during chlorination, which is useful for risk control and optimization of the chlorination process.
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Benzofenonas , Daphnia , Desinfección , Halogenación , Sustancias Húmicas , Contaminantes Químicos del Agua , Pez Cebra , Animales , Daphnia/efectos de los fármacos , Desinfección/métodos , Benzofenonas/toxicidad , Contaminantes Químicos del Agua/toxicidad , Purificación del Agua/métodos , Cloro/toxicidad , Cloro/química , Rayos Ultravioleta , Frecuencia Cardíaca/efectos de los fármacos , Daphnia magnaRESUMEN
Ultrafiltration (UF) is widely used in drinking water plants; however, membrane fouling is unavoidable. Natural organic matter (NOM) is commonly considered as an important pollutant that causes membrane fouling. Herein, we proposed VUV/H2O2 as a UF pretreatment and used UV/H2O2 for comparison. Compared to UV/H2O2, the VUV/H2O2 system presented superior NOM removal. In the VUV/H2O2 system, the steady-state concentration of HO⢠was approximately twice that in the UV/H2O2 system, which was ascribed to the promoting effect of the 185 nm photons. Specifically, 185 nm photons promoted HO⢠generation by decomposing mainly H2O at a low H2O2 dose or by decomposing mainly H2O2 at a high H2O2 dose. The VUV/H2O2 pretreatment also demonstrated better membrane fouling mitigation performance than did UV/H2O2. An increase in the H2O2 dose promoted HO⢠generation, thereby enhancing the performance of NOM degradation and membrane fouling alleviation and shifting the major membrane fouling mechanism from cake filtration to standard blocking. The VUV/H2O2 (0.60 mM) pretreatment effectively reduced disinfection byproducts (DBPs) formation during chlorine disinfection. Additionally, the oxidant H2O2 affected the membrane surface morphology and performance but had no evident effect on the mechanical properties. In actual water treatment, the VUV/H2O2 pretreatment exhibited better performance than the UV/H2O2 pretreatment in easing membrane fouling, ameliorating water quality, and reducing DBPs formation and acute toxicity.
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Desinfección , Peróxido de Hidrógeno , Ultrafiltración , Rayos Ultravioleta , Purificación del Agua , Peróxido de Hidrógeno/química , Purificación del Agua/métodos , Desinfección/métodos , Membranas Artificiales , Contaminantes Químicos del Agua/toxicidad , Contaminantes Químicos del Agua/química , Desinfectantes/toxicidad , Desinfectantes/química , Cloro/química , Cloro/toxicidad , Aliivibrio fischeri/efectos de los fármacosRESUMEN
Heavy infestation by Perna viridis has been observed in the sub-seabed seawater intake tunnel and CWS of a tropical coastal power station in-spite of continuous low dose chlorination regime (0.2 ± 0.1 mg L-1) (CLDC), indicating periodical settlement and growth. Continuous arrival of mussels (colonized in the sub seabed tunnel intake section) at the pump house indicated that the mussels were able to tolerate and survive in a chlorinated environment, for varying time periods and were dislodged when they become weak and subsequent death, leading to flushing out of the system. In the present study, effect of continuous chlorination [0.2 mg L-1 (in-plant use); 0.5 mg L-1 (shock dose) & 1.0 mg L-1 (high levels)] was evaluated on mussels to assess; (a) time taken for mortality, (b) action of chlorine on physiological, genetic, metabolic and neuronal processes. 100% mortality of mussels was observed after 15 (0.2 mg L-1); 9 (0.5 mg L-1) and 6 days (1.0 mg L-1) respectively. Extended valve closure due to chlorination resulted in stress, impairing the respiratory and feeding behavior leading to deterioration in mussel health. Pseudofaeces excretion reduced to 68% (0.2 mg L-1); 10% (0.5 mg L-1) and 89% (1.0 mg L-1) compared to controls. Genotoxicity was observed with increase in % tail DNA fraction in all treatments such as 86% (0.2 mg L-1); 76% (0.5 mg L-1) and 85% (1.0 mg L-1). Reactive Oxygen Species (ROS) stress biomarkers increased drastically/peaked within the first 3 days of continuous chlorination with subsequent quenching by antioxidant enzymes. Gill produced highest generation of ROS; 38% (0.2 mg L-1); 97% (0.5 mg L-1); 98% (1.0 mg L-1). Additionally, it was shown that 84% (0.2 mg L-1), 72% (0.5 mg L-1), and 80.4% (1.0 mg L-1) of the neurotransmitter acetylcholinesterase activity was inhibited by chlorine at the nerve synapse. The cumulative impact of ROS generation, neuronal toxicity, and disrupted functions weakens the overall health of green mussels resulting in mortality.
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Halogenación , Perna , Contaminantes Químicos del Agua , Animales , Perna/fisiología , Perna/efectos de los fármacos , Perna/metabolismo , Contaminantes Químicos del Agua/toxicidad , Cloro/toxicidad , Cloro/química , Agua de Mar/química , Daño del ADNRESUMEN
As a regulator of alveolo-capillary barrier integrity, Transient Receptor Potential Vanilloid 4 (TRPV4) antagonism represents a promising strategy for reducing pulmonary edema secondary to chemical inhalation. In an experimental model of acute lung injury induced by exposure of anesthetized swine to chlorine gas by mechanical ventilation, the dose-dependent effects of TRPV4 inhibitor GSK2798745 were evaluated. Pulmonary function and oxygenation were measured hourly; airway responsiveness, wet-to-dry lung weight ratios, airway inflammation, and histopathology were assessed 24 h post-exposure. Exposure to 240 parts per million (ppm) chlorine gas for ≥50 min resulted in acute lung injury characterized by sustained changes in the ratio of partial pressure of oxygen in arterial blood to the fraction of inspiratory oxygen concentration (PaO2/FiO2), oxygenation index, peak inspiratory pressure, dynamic lung compliance, and respiratory system resistance over 24 h. Chlorine exposure also heightened airway response to methacholine and increased wet-to-dry lung weight ratios at 24 h. Following 55-min chlorine gas exposure, GSK2798745 marginally improved PaO2/FiO2, but did not impact lung function, airway responsiveness, wet-to-dry lung weight ratios, airway inflammation, or histopathology. In summary, in this swine model of chlorine gas-induced acute lung injury, GSK2798745 did not demonstrate a clinically relevant improvement of key disease endpoints.
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Lesión Pulmonar Aguda , Antineoplásicos , Bencimidazoles , Compuestos de Espiro , Animales , Porcinos , Cloro/toxicidad , Canales Catiónicos TRPV , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/tratamiento farmacológico , Inflamación , OxígenoRESUMEN
Chlorine (Cl2) exposure poses a significant risk to ocular health, with the cornea being particularly susceptible to its corrosive effects. Antioxidants, known for their ability to neutralize reactive oxygen species (ROS) and alleviate oxidative stress, were explored as potential therapeutic agents to counteract chlorine-induced damage. In vitro experiments using human corneal epithelial cells showed decreased cell viability by chlorine-induced ROS production, which was reversed by antioxidant incubation. The mitochondrial membrane potential decreased due to both low and high doses of Cl2 exposure; however, it was recovered through antioxidants. The wound scratch assay showed that antioxidants mitigated impaired wound healing after Cl2 exposure. In vivo and ex vivo, after Cl2 exposure, increased corneal fluorescein staining indicates damaged corneal epithelial and stromal layers of mice cornea. Likewise, Cl2 exposure in human ex vivo corneas led to corneal injury characterized by epithelial fluorescein staining and epithelial erosion. However, antioxidants protected Cl2-induced damage. These results highlight the effects of Cl2 on corneal cells using in vitro, ex vivo, and in vivo models while also underscoring the potential of antioxidants, such as vitamin A, vitamin C, resveratrol, and melatonin, as protective agents against acute chlorine toxicity-induced corneal injury. Further investigation is needed to confirm the antioxidants' capacity to alleviate oxidative stress and enhance the corneal healing process.
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Antioxidantes , Lesiones de la Cornea , Humanos , Animales , Ratones , Antioxidantes/metabolismo , Cloro/toxicidad , Especies Reactivas de Oxígeno/metabolismo , Córnea/metabolismo , Fluoresceína/farmacologíaRESUMEN
Chlorine gas (Cl2) has been repeatedly used as a chemical weapon, first in World War I and most recently in Syria. Life-threatening Cl2 exposures frequently occur in domestic and occupational environments, and in transportation accidents. Modeling the human etiology of Cl2-induced acute lung injury (ALI), forensic biomarkers, and targeted countermeasures development have been hampered by inadequate large animal models. The objective of this study was to develop a translational model of Cl2-induced ALI in swine to understand toxico-pathophysiology and evaluate whether it is suitable for screening potential medical countermeasures and to identify biomarkers useful for forensic analysis. Specific pathogen-free Yorkshire swine (30-40 kg) of either sex were exposed to Cl2 (≤240 ppm for 1 h) or filtered air under anesthesia and controlled mechanical ventilation. Exposure to Cl2 resulted in severe hypoxia and hypoxemia, increased airway resistance and peak inspiratory pressure, and decreased dynamic lung compliance. Cl2 exposure resulted in increased total leucocyte and neutrophil counts in bronchoalveolar lavage fluid, vascular leakage, and pulmonary edema compared with the air-exposed group. The model recapitulated all three key histopathological features of human ALI, such as neutrophilic alveolitis, deposition of hyaline membranes, and formation of microthrombi. Free and lipid-bound 2-chlorofatty acids and chlorotyrosine-modified proteins (3-chloro-l-tyrosine and 3,5-dichloro-l-tyrosine) were detected in plasma and lung tissue after Cl2 exposure. In this study, we developed a translational swine model that recapitulates key features of human Cl2 inhalation injury and is suitable for testing medical countermeasures, and validated chlorinated fatty acids and protein adducts as biomarkers of Cl2 inhalation.NEW & NOTEWORTHY We established a swine model of chlorine gas-induced acute lung injury that exhibits several features of human acute lung injury and is suitable for screening potential medical countermeasures. We validated chlorinated fatty acids and protein adducts in plasma and lung samples as forensic biomarkers of chlorine inhalation.
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Lesión Pulmonar Aguda , Cloro , Humanos , Animales , Porcinos , Cloro/toxicidad , Cloro/metabolismo , Pulmón/metabolismo , Líquido del Lavado Bronquioalveolar , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/patología , Biomarcadores/metabolismo , Ácidos Grasos/metabolismoRESUMEN
Exhaled breath (EB) contains various volatile organic compounds (VOCs) that can indicate specific biological or pathological processes in the body. Analytical techniques like gas chromatography-mass spectrometry (GC-MS) can be used to detect and measure these exhaled biomarkers. In this study, the objective was to develop a non-invasive method of EB sampling in animals that were awake, as well as to analyze EB for volatile biomarkers specific for chlorine exposure and/or diagnostic biomarkers for chlorine-induced acute lung injury (ALI). To achieve this, a custom-made sampling device was used to collect EB samples from 19 female Balb/c mice. EB was sampled both pre-exposure (serving as internal control) and 30 min after exposure to chlorine. EB was collected on thermal desorption tubes and subsequently analyzed for VOCs by GC-MS. The following day, the extent of airway injury was assessed in the animals by examining neutrophils in the bronchoalveolar lavage fluid. VOC analysis revealed alterations in the EB biomarker pattern post-chlorine exposure, with eight biomarkers displaying increased levels and six exhibiting decreased levels following exposure. Four chlorinated compounds: trichloromethane, chloroacetone, 1,1-dichloroacetone and dichloroacetonitrile, were increased in chlorine-exposed mice, suggesting their specificity as chlorine EB biomarkers. Furthermore, chlorine-exposed mice displayed a neutrophilic inflammatory response and body weight loss 24 h following exposure. In conclusion, all animals developed an airway inflammation characterized by neutrophil infiltration and a specific EB pattern that could be extracted after chlorine exposure. Monitoring EB samples can readily and non-invasively provide valuable information on biomarkers for diagnosis of chlorine-induced ALI, confirming chlorine exposures.
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Cloro , Compuestos Orgánicos Volátiles , Femenino , Animales , Ratones , Cloro/toxicidad , Pruebas Respiratorias/métodos , Espiración , Cromatografía de Gases y Espectrometría de Masas/métodos , Biomarcadores/análisis , Compuestos Orgánicos Volátiles/análisisRESUMEN
Inhaled toxicants are used for diverse purposes, ranging from industrial applications such as agriculture, sanitation, and fumigation to crowd control and chemical warfare, and acute exposure can induce lasting respiratory complications. The intentional release of chemical warfare agents (CWAs) during World War I caused life-long damage for survivors, and CWA use is outlawed by international treaties. However, in the past two decades, chemical warfare use has surged in the Middle East and Eastern Europe, with a shift toward lung toxicants. The potential use of industrial and agricultural chemicals in rogue activities is a major concern as they are often stored and transported near populated areas, where intentional or accidental release can cause severe injuries and fatalities. Despite laws and regulatory agencies that regulate use, storage, transport, emissions, and disposal, inhalational exposures continue to cause lasting lung injury. Industrial irritants (e.g., ammonia) aggravate the upper respiratory tract, causing pneumonitis, bronchoconstriction, and dyspnea. Irritant gases (e.g., acrolein, chloropicrin) affect epithelial barrier integrity and cause tissue damage through reactive intermediates or by direct adduction of cysteine-rich proteins. Symptoms of CWAs (e.g., chlorine gas, phosgene, sulfur mustard) progress from airway obstruction and pulmonary edema to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), which results in respiratory depression days later. Emergency treatment is limited to supportive care using bronchodilators to control airway constriction and rescue with mechanical ventilation to improve gas exchange. Complications from acute exposure can promote obstructive lung disease and/or pulmonary fibrosis, which require long-term clinical care. SIGNIFICANCE STATEMENT: Inhaled chemical threats are of growing concern in both civilian and military settings, and there is an increased need to reduce acute lung injury and delayed clinical complications from exposures. This minireview highlights our current understanding of acute toxicity and pathophysiology of a select number of chemicals of concern. It discusses potential early-stage therapeutic development as well as challenges in developing countermeasures applicable for administration in mass casualty situations.
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Lesión Pulmonar Aguda , Sustancias para la Guerra Química , Fosgeno , Humanos , Pulmón , Cloro/farmacología , Cloro/toxicidad , Sustancias para la Guerra Química/toxicidad , Fosgeno/metabolismo , Fosgeno/farmacología , Lesión Pulmonar Aguda/metabolismo , IrritantesRESUMEN
Chlorine is a toxic industrial chemical that has been used as a chemical weapon in recent armed conflicts. Confirming human exposure to chlorine has proven challenging, and there is currently no established method for analyzing human biomedical samples to unambiguously verify chlorine exposure. In this study, two chlorine-specific biomarkers: palmitoyl-oleoyl phosphatidylglycerol chlorohydrin (POPG-HOCl) and the lipid derivative oleoyl ethanolamide chlorohydrin (OEA-HOCl) are shown in bronchoalveolar lavage fluid (BALF) samples from spontaneously breathing pigs after chlorine exposure. These biomarkers are formed by the chemical reaction of chlorine with unsaturated phospholipids found in the pulmonary surfactant, which is present at the gas-liquid interface within the lung alveoli. Our results strongly suggest that lipid chlorohydrins are promising candidate biomarkers in the development of a verification method for chlorine exposure. The establishment of verified methods capable of confirming the illicit use of toxic industrial chemicals is crucial for upholding the principles of the Chemical Weapons Convention (CWC) and enforcing the ban on chemical weapons. This study represents the first published dataset in BALF revealing chlorine biomarkers detected in a large animal. Furthermore, these biomarkers are distinct in that they originate from molecular chlorine rather than hypochlorous acid.
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Clorhidrinas , Etanolamina , Ácidos Oléicos , Fosfolípidos , Humanos , Animales , Porcinos , Cloro/toxicidad , Clorhidrinas/química , Líquido del Lavado Bronquioalveolar , BiomarcadoresRESUMEN
Characterization of the pathophysiology of ARDS following chlorine gas inhalation in clinically relevant translational large animal models is essential, as the opportunity for clinical trials in this type of trauma is extremely limited. To investigate Cl2 concentration and gender-dependent ARDS severity. Sheep (n = 54) were exposed to air or Cl2 premixed in air at a concentration of 50, 100, 200, and 300 ppm for 30 min under anesthesia/analgesia and monitored for an additional 48 h in a conscious state. Cardiopulmonary variables and survival endpoints were compared between male and female sheep. Overall there were no significant differences in the responses of female and male sheep except pulmonary oxygenation tended to be better in the male sheep (300 ppm group), and the pulmonary arterial pressure was lower (200 ppm group). The onset of mild ARDS (200 < PaO2/FiO2 ≤ 300) was observed at 36 h post exposure in the 50 ppm group, whereas the 100 ppm group developed mild and moderate (100 ≤ PaO2/FiO2 ≤ 200) ARDS by 12 and 36 h after injury, respectively. The 200 ppm and 300 ppm groups developed moderate ARDS within 6 and 3 h after injury, respectively. The 300 ppm group progressed to severe (PaO2/FiO2 ≤ 100) ARDS at 18 h after injury. Increases in pPeak and pPlateau were noted in all injured animals. Compared to sham, inhalation of 200 ppm and 300 ppm Cl2 significantly increased lung extravascular water content. The thoracic cavity fluid accumulation dose-dependently increased with the severity of trauma as compared to sham. At necropsy, the lungs were red, heavy, solidified, and fluid filled; the injury severity grew with increasing Cl2 concentration. The severity of ARDS and mortality rate directly correlated to inhaled Cl2 concentrations. No significant sex-dependent differences were found in measured endpoint variables.
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Cloro , Síndrome de Dificultad Respiratoria , Masculino , Femenino , Animales , Ovinos , Cloro/toxicidad , Cloro/uso terapéutico , Pulmón , Administración por InhalaciónRESUMEN
The objective of this study was to explore the effects of antioxidant treatments, specifically N-acetylcysteine (NAC) and N-acetylcysteine amide (NACA), in a mouse model of chlorine (Cl2)-induced lung injury. Additionally, the study aimed to investigate the utility of pig precision-cut lung slices (PCLS) as an ex vivo alternative for studying the short-term effects of Cl2 exposure and evaluating antioxidant treatments. The toxicological responses were analyzed in Cl2-exposed mice (inflammation, airway hyperresponsiveness (AHR)) and PCLS (viability, cytotoxicity, inflammatory mediators). Airways contractions were assessed using a small ventilator for mice and electric-field stimulation (EFS) for PCLS. Antioxidant treatments were administered to evaluate their effects. In Cl2-exposed mice, NAC treatment did not alleviate AHR, but it did reduce the number of neutrophils in bronchoalveolar lavage fluid and inflammatory mediators in lung tissue. In PCLS, exposure to Cl2 resulted in concentration-dependent toxicity, impairing the lung tissue's ability to respond to EFS-stimulation. NAC treatment increased viability, mitigated the toxic responses caused by Cl2 exposure, and maintained contractility comparable to unexposed controls. Interestingly, NACA did not provide any additional treatment effect beyond NAC in both models. In conclusion, the establishment of a pig model for Cl2-induced lung damage supports further investigation of NAC as a potential treatment. However, the lack of protective effects on AHR after NAC treatment in mice suggests that NAC alone may not be sufficient as a complete treatment for Cl2 injuries. Optimization of existing medications with a polypharmacy approach may be more successful in addressing the complex sequelae of Cl2-induced lung injury.
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Acetilcisteína , Lesión Pulmonar , Ratones , Animales , Porcinos , Acetilcisteína/farmacología , Acetilcisteína/uso terapéutico , Cloro/toxicidad , Lesión Pulmonar/inducido químicamente , Lesión Pulmonar/tratamiento farmacológico , Lesión Pulmonar/prevención & control , Antioxidantes/farmacología , Pulmón , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Mediadores de InflamaciónRESUMEN
INTRODUCTION: Hemodialysis uses municipal water that must be strictly purified and sterilized to be used for that procedure. Large amounts of decontaminants are often used, such as chlorine, and if these compounds are not subsequently removed they can be transferred to the blood of patients causing complications including methemoglobinemia. METHODS: In this case series study, dialysis patients in one unit were evaluated. We reviewed clinical characteristics and laboratory findings obtained on the day when the water supply was disinfected with chlorine, with the aim to quantify methemoglobin concentrations. Our objective was to characterize the clinical presentation and management of patients who presented with methemoglobinemia on a specific index day. We also reviewed reported cases in the literature regarding this underreported complication. RESULTS: Eight patients who presented with chlorine intoxication were evaluated. The methemoglobin concentrations were between 1.3% and 7.9% (reference value 0-1%). We believe this to be caused by water containing 0.78 mg/L of total chlorine. Seven patients presented with cyanosis, 4 with dizziness, 6 with dark brown blood, 4 with dyspnea, and 4 with headache and hemolytic anemia. Subjects were treated with supplemental oxygen, methylene blue, intravenous vitamin C, blood transfusions, and increased doses of erythropoietin. No patient died, and all continued with their usual hemodialysis sessions. CONCLUSION: Acute chlorine intoxication transferred by the water used during hemodialysis sessions can present with methemoglobinemia accompanied by cyanosis, oxygen desaturation, and hemolytic anemia. Chlorine levels should be carefully monitored in the water used for hemodialysis treatment.
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Anemia Hemolítica , Metahemoglobinemia , Humanos , Metahemoglobinemia/inducido químicamente , Metahemoglobinemia/terapia , Metahemoglobina/uso terapéutico , Cloro/toxicidad , Diálisis Renal/efectos adversos , Cianosis/complicaciones , Cloruros , Anemia Hemolítica/complicaciones , Oxígeno , AguaRESUMEN
Diethylamino hydroxybenzoyl hexyl benzoate (DHHB), an ultraviolet (UV) filter, can be found in sunscreens and other personal care products and thus can be introduced into swimming pools through the swimmers. In outdoor pools, DHHB will inevitably interact with free chlorine and sunlight. Therefore, the mechanism of solarchlorine chemical transformation of DHHB, as well as the environmental risk, were investigated in this work. In chlorinated with solar (Cl + solar) process, free chlorine was the dominant contributor to 85% of the DHHB degradation, while hydroxyl radicals and reactive chlorine species contributed only 15% because of low free radical generation and fast DHHB and free chlorine reaction rates. Scavenging matrices, such as Cl-, NH4+, and dissolved organic matter (DOM), inhibited the degradation of DHHB in the Cl + solar process, while Br-, HCO3-, NO3-, and urea promoted DHHB degradation. DHHB degradation was inhibited in tap water swimming pool samples, while it was enhanced in seawater pool samples by the Cl + solar process. Seven transformation by-products (TBPs) including mono-, dichlorinated, dealkylate, and monochloro-hydroxylated TBPs were identified. Three degradation pathways, chlorine substitution, chlorine and hydroxyl substitution, and dealkylation were proposed for DHHB transformation in the Cl + solar process. Both Quantitative structure-activity relationship and Aliivibrio fischeri toxicity tests demonstrated increased toxicity for the chlorinated TBPs. A risk assessment of the DHHB and its TBPs suggested that both DHHB and its chlorinated TBPs pose a significant health risk.
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Piscinas , Contaminantes Químicos del Agua , Purificación del Agua , Cloro/toxicidad , Rayos Ultravioleta , Protectores Solares/toxicidad , Agua , Contaminantes Químicos del Agua/toxicidad , Contaminantes Químicos del Agua/análisis , Cinética , Oxidación-ReducciónRESUMEN
Polychlorinated biphenyls (PCBs) with different chlorine substitution patterns often coexist in e-waste-processing sites. However, the single and combined toxicity of PCBs to soil organisms and the influence of chlorine substitution patterns remain largely unknown. Herein, we evaluated the distinct in vivo toxicity of PCB28 (a trichlorinated PCB), PCB52 (a tetrachlorinated PCB), PCB101 (a pentachlorinated PCB), and their mixture to earthworm Eisenia fetida in soil, and looked into the underlining mechanisms in an in vitro test using coelomocytes. After a 28-days exposure, all PCBs (up to 10 mg/kg) were not fatal to earthworms, but could induce intestinal histopathological changes and microbial community alterations in the drilosphere system, along with a significant weight loss. Notably, pentachlorinated PCBs with a low bioaccumulation ability showed greater inhibitory effects on the growth of earthworm than lowly chlorinated PCBs, suggesting that bioaccumulation was not the main determinant of chlorine substitution-dependent toxicity. Furthermore, in vitro assays showed that the highly chlorinated PCBs induced a high-percentage apoptosis of eleocytes in the coelomocytes and significantly activated antioxidant enzymes, indicating that the distinct cellular vulnerability to lowly/highly chlorinated PCBs was the main contributor to the PCBs toxicity. These findings emphasize the specific advantage of using earthworms in the control of lowly chlorinated PCBs in soil due to their high tolerance and accumulation ability.
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Oligoquetos , Bifenilos Policlorados , Contaminantes del Suelo , Animales , Cloro/toxicidad , Bifenilos Policlorados/toxicidad , Bifenilos Policlorados/análisis , Suelo , Contaminantes del Suelo/toxicidad , Contaminantes del Suelo/análisis , Halógenos/farmacologíaRESUMEN
Chlorine (Cl2) is a disinfectant often used in swimming pools and water treatment facilities. However, it is released into aquatic ecosystems, where it may harm non-targeted organisms. Here, we performed a mesocosm experiment exposing Zacco platypus (Z. platypus) to biocide Cl2 for 30 days (30 d) at two days' time points 15 days (15 d) and 30 d samples were collected. Here, Z. platypus was exposed to a sublethal concentration (0.1 mg/L) of Cl2, and comparative transcriptomics analyses were performed to determine their response mechanisms at the molecular level. According to RNA sequencing of the whole-body transcriptome, 860 and 1189 differentially expressed genes (DEGs) were identified from the 15 d and 30 d responses to Cl2, respectively. After enrichment analysis of GO (Gene Ontology) functions and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways, identified DEGs were demonstrated to be associated with a variety of functions, including "ion binding and transmembrane transporters". Cl2 also induced oxidative stress in Z. platypus by increasing the levels of reactive oxygen species (ROS) while decreasing the catalase (CAT) content and the levels of solute carrier family 22 member 11 (slc22a11), Caspase-8 (casp-8), inducible nitric oxide synthase (NOS2), cytosolic phospholipase A2 gamma (PLA2G4). However, Z. platypus still allows recovery during stress suspension by increasing the expression levels of solute carrier family proteins. The GO and KEGG annotation results revealed that the expression of DEGs were related to the detoxification process, immune response, and antioxidant mechanism. Additionally, protein-protein interaction networks (PPI) and cytoHubba analyses identified sixteen hub genes and their interaction. These findings elucidate the regulation of various DEGs and signaling pathways in response to Cl2 exposure, which will improve our knowledge and laid foundation for further investigation of the toxicity of Cl2 to Z. platypus.
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Desinfectantes , Ornitorrinco , Animales , Transcriptoma , Cloro/toxicidad , Desinfectantes/toxicidad , Ecosistema , Perfilación de la Expresión Génica/métodos , Biología Computacional/métodosRESUMEN
Chlorine (Cl2) gas is a highly toxic and oxidizing irritant that causes life-threatening lung injuries. Herein, we investigated the impact of Cl2-induced injury and oxidative stress on lung macrophage phenotype and function. Spontaneously breathing male C57BL/6J mice were exposed to air or Cl2 (300 ppm, 25 min) in a whole-body exposure chamber. Bronchoalveolar lavage (BAL) fluid and cells, and lung tissue were collected 24 h later and analyzed for markers of injury, oxidative stress and macrophage activation. Exposure of mice to Cl2 resulted in increases in numbers of BAL cells and levels of IgM, total protein, and fibrinogen, indicating alveolar epithelial barrier dysfunction and inflammation. BAL levels of inflammatory proteins including surfactant protein (SP)-D, soluble receptor for glycation end product (sRAGE) and matrix metalloproteinase (MMP)-9 were also increased. Cl2 inhalation resulted in upregulation of phospho-histone H2A.X, a marker of double-strand DNA breaks in the bronchiolar epithelium and alveolar cells; oxidative stress proteins, heme oxygenase (HO)-1 and catalase were also upregulated. Flow cytometric analysis of BAL cells revealed increases in proinflammatory macrophages following Cl2 exposure, whereas numbers of resident and antiinflammatory macrophages were not altered. This was associated with increases in numbers of macrophages expressing cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS), markers of proinflammatory activation, with no effect on mannose receptor (MR) or Ym-1 expression, markers of antiinflammatory activation. Metabolic analysis of lung cells showed increases in glycolytic activity following Cl2 exposure in line with proinflammatory macrophage activation. Mechanistic understanding of Cl2-induced injury will be useful in the identification of efficacious countermeasures for mitigating morbidity and mortality of this highly toxic gas.
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Cloro , Lesión Pulmonar , Ratones , Masculino , Animales , Cloro/toxicidad , Ratones Endogámicos C57BL , Pulmón , Macrófagos , Líquido del Lavado Bronquioalveolar , Estrés Oxidativo , Metabolismo EnergéticoRESUMEN
Chlorine (Cl2) gas is a toxic industrial chemical (TIC) that poses a hazard to human health following accidental and/or intentional (e.g. terrorist) release. By using a murine model of sub-lethal Cl2 exposure we have examined the airway hyper responsiveness, cellular infiltrates, transcriptomic and proteomic responses of the lung. In the "crisis" phase at 2 h and 6 h there is a significant decreases in leukocytes within bronchoalveolar lavage fluid accompanied by an upregulation within the proteome of immune pathways ultimately resulting in neutrophil influx at 24 h. A flip towards "repair" in the transcriptome and proteome occurs at 24 h, neutrophil influx and an associated drop in the lung function persisting until 14 d post-exposure and subsequent "recovery" after 28 days. Collectively, this research provides new insights into the mechanisms of damage, early global responses and processes of repair induced in the lung following the inhalation of Cl2.
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Cloro , Proteoma , Ratones , Humanos , Animales , Cloro/toxicidad , Proteómica , Pulmón , Líquido del Lavado BronquioalveolarRESUMEN
OBJECTIVE: Chlorine (Cl2), as an asphyxiant toxicant, induced poisoning incidents and acute lung injury (ALI) occur frequently. The specific pathogenesis of Cl2-induced ALI remains unclear. Immune cells play an important role in the process of lung damage. We used single-cell RNA sequencing (scRNA-seq) technology to explore T cells and macrophages molecular mechanism. METHODS: Female BALB/c mice were exposed to 400 ppm Cl2 for 15 min. scRNA-seq technology was used to observe the heterogeneity of T cells and macrophages. Hematoxylin-eosin (H&E) staining was used to evaluate the degree of lung injury. Immunofluorescence was used to verify the highly expressed genes of our interest. RESULTS: A total of 5316 to 7742 cells were classified into eight different cell types. Several new highly expressed anti-inflammatory and pro-inflammatory genes were found in T cells and macrophages, which were further verified in vitro. Through the pseudotime analysis of macrophages, it was found that the expression of pro-inflammatory and anti-inflammatory genes showed opposite trends in the development of Cl2-induced ALI. This study also mapped T cells-macrophage communication and identified the development of several important receptor-ligand complexes in Cl2-induced ALI. CONCLUSIONS: These findings are worthy of further exploration and provide new resources and directions for the study of Cl2-induced ALI in mice, especially in immune and inflammation mechanisms.
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Lesión Pulmonar Aguda , Cloro , Ratones , Femenino , Animales , Cloro/toxicidad , Linfocitos T , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/genética , Pulmón/patología , Ratones Endogámicos BALB C , Antiinflamatorios/farmacología , Macrófagos , Análisis de Secuencia de ARN , Lipopolisacáridos/toxicidadRESUMEN
Azithromycin (AZM), an antibacterial considered one of the most consumed drugs, especially during the period against the Covid 19 pandemic, and it is one of the persistent contaminants that can be released into aquatic ecosystems. The purpose of this study is to determine the efficacy of a Fenton-like process (chlorine/iron) for the degradation of AZM in an aqueous medium by determining the impact of several factors (the initial concentration of (FeSO4, NaClO, pollutant), and the initial pH) on the degradation rate. The Response Surface Methodology (RSM) based on the Box-Wilson design as well as the Artificial Neural Network (ANN) modeling combined with a genetic algorithm (GA) approaches were used to determine the optimal levels of the selected variables and the optimal rate of degradation. The quadratic model of multi-linear regression developed indicated that the optimal conditions were a concentration of chlorine of 600 µM, the concentration of AZM is 32.8 mg/L, the mass of the catalyst FeSO4 is 3.5 mg and a pH of 2.5, these optimal values gave a predicted and experimental yield of 64.05% and 70% respectively, the lack of fit test in RSM modeling (F0 = 3.31 which is inferior to Fcritic (0.05, 10.4) = 5.96) indicates that the true regression function is not linear therefore, the ANN-GA modeling as non-linear regression indicated that the optimal conditions were a concentration of chlorine of 256 µM, the concentration of AZM is 5 mg/L, the mass of the catalyst FeSO4 is 9.5 mg and a pH of 2.8, these optimal values gave a predicted and experimental yield of 79.69% and close to 80% respectively, Furthermore, biotoxicity tests were conducted to confirm the performance of our process using bio-indicators called daphnia (Daphnia magna), which demonstrated the efficacy of the like-Fenton process after 4 h of degradation.
Asunto(s)
Tratamiento Farmacológico de COVID-19 , Daphnia , Animales , Azitromicina/toxicidad , Cloro/toxicidad , Ecosistema , Redes Neurales de la Computación , AguaRESUMEN
RATIONALE: Exercise-induced bronchoconstriction (EIB) is defined as acute narrowing of the airways during or immediately after exercise. EIB has a high prevalence in elite swimmers probably due to the high ventilation rate and exposure to the chlorine by-products. It is still puzzling which pathophysiological mechanisms drive EIB. OBJECTIVE: In this study, we evaluated airway hyperreactivity, permeability, integrity and inflammation in a murine swimmers EIB model with and without chlorine exposure. METHODS: Mice performed a 3-week swimming protocol in a swimming pool with counter current. Three hours after the last swimming session, airway hyperreactivity to methacholine was assessed. Cytokine levels and cellular differential analysis was performed in BAL fluid. Airway permeability and tight junction expression was measured in serum and lung tissue. T-, B-, dendritic and innate lymphoid cells were determined in lung tissue via flow cytometry. RESULTS: A significant higher airway resistance (Rn; P < 0.0001) was observed in mice swimming in chlorinated water (mean Rn = 1.26 cmH2O.s/ml) compared to mice swimming in tap water (mean Rn = 0.76 cmH2O.s/ml) and both inhalation groups in the absence of cellular inflammation. No significant differences were found in lung immune cell populations or in lung tight junction mRNA expression. Experiments in SCID, Rag2-/-γc-/- or Cpa3cre/+ mice showed a limited involvement of the innate, adaptive immune system or the mast cells. CONCLUSION: Our 3-week swimming murine model mimics intensive swimming in chlorinated water with the presence of airway hyperreactivity in mice swimming in chlorinated water in the absence of airway inflammation and airway epithelial damage.