RESUMO
Lanthanum (La) and cerium (Ce), rare earth elements with physical properties similar to calcium (Ca), are generally considered non-toxic when used appropriately. However, their ions possess anti-tumor capabilities. This investigation explores the potential applications and mechanisms of LaCl3 or CeCl3 treatment in triple-negative breast cancer (TNBC) cell lines. TNBC, characterized by the absence of estrogen receptor (ERα), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) expression, is prone to early metastasis and resistant to hormone therapy. Our results demonstrate that La/Ce treatment reduces cell growth, and when combined with cisplatin, it synergistically inhibits cell growth and the PI3K/AKT pathway. La and Ce induce oxidative stress by disrupting mitochondrial function, leading to protein oxidation. Additionally, they interfere with protein homeostasis and induce nucleolar stress. Furthermore, disturbance in F-actin web formation impairs cell migration. This study delves into the mechanism by which calcium-like elements La and Ce inhibit breast cancer cell growth, shedding light on their interference in mitochondrial function, protein homeostasis, and cytoskeleton assembly.
Assuntos
Elementos da Série dos Lantanídeos , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Cálcio , Cisplatino , Lantânio/toxicidade , Linhagem Celular TumoralRESUMO
Lanthanum can induce neurotoxicity and impair cognitive function; therefore, research on the mechanism by which the ability to learning and memory is decreased by lanthanum is vitally important for protecting health. Microglia are a type of neuroglia located throughout the brain and spinal cord that play an important role in the central nervous system. When overactive, these cells can cause the excessive production of inflammatory cytokines that can damage neighboring neurons. The purpose of this study was to explore the effect of lanthanum in the form of lanthanum chloride (LaCl3) on learning and the memory of mice and determine whether there is a relationship between hippocampal neurons or learning and memory damage and excessive production of inflammatory cytokines. Four groups of pregnant Chinese Kun Ming mice were exposed to 0, 18, 36, or 72 mM LaCl3 in their drinking water during lactation. The offspring were then exposed to LaCl3 in the breast milk at birth until weaning and then exposed to these concentrations in their drinking water for 2 months after weaning. The results showed that LaCl3 impaired learning and memory in mice and injured their neurons, activated the microglia, and significantly overregulated the mRNA and protein expression of tumor necrosis factor alpha, interleukin (IL)-1ß, IL-6, monocyte chemoattractant protein-1, and nitric oxide in the hippocampus. The results of this study suggest that lanthanum can impair learning and memory in mice, possibly by over-activating the microglia.
Assuntos
Lantânio , Microglia , Animais , Feminino , Hipocampo/metabolismo , Lantânio/metabolismo , Lantânio/toxicidade , Aprendizagem em Labirinto , Gravidez , Ratos , Ratos Wistar , Transdução de SinaisRESUMO
Autophagy is a lysosome dependent degradation pathway occurring in eukaryotic cells. Autophagy ensures balance and survival mechanism of cells during harmful stress. Excessive or weak autophagy leads to abnormal function and death in some cases. Lanthanum (La), a rare earth element (REE), damages the central nervous system (CNS) and promotes learning and memory dysfunction. However, underlying mechanism has not been fully elucidated. La induces oxidative stress, inhibits Nrf2/ARE and Akt/mTOR signaling pathways, and activates JNK/c-Jun and JNK/Foxo signaling pathways, resulting in abnormal induction of autophagy in rat hippocampus. In addition, La activates PINK1- Parkin signaling pathway and induces mitochondrial autophagy. However, the relationship between La and autophagy in rat neurons at the cellular level has not been explored previously. The aim of this study was to explore adverse effects of La. Primary culture of rat neurons were exposed to 0 mmol/L, 0.025 mmol/L, 0.05 mmol/L and 0.1 mmol/L lanthanum chloride (LaCl3). The results showed that La upregulates p-AMPK, inhibits levels of p-Akt and p-mTOR, increases levels of autophagy related proteins (Beclin1 and LC3B-II), and downregulates expression of p-Bcl-2 and p62. Upstream and downstream intervention agents of autophagy were used to detect autophagy flux to verify accuracy of our results. Electron microscopy results showed significant increase in the number of autophagosomes in LaCl3 exposed groups. These findings imply that LaCl3 inhibits Akt/mTOR signaling pathway and activates AMPK/mTOR signaling pathway, resulting in abnormal autophagy in primary cultured rat cortical neurons. In addition, LaCl3 induces neuronal damage through excessive autophagy.
Assuntos
Autofagia/efeitos dos fármacos , Lantânio/toxicidade , Neurônios , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Células Cultivadas , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Serina-Treonina Quinases TOR/metabolismoRESUMO
Nanoparticles have a great potential to increase the therapeutic efficiency of several cancer therapies. This research examines the potential for silver-doped lanthanum manganite nanoparticles to enhance radiation therapy to target radioresistant brain cancer cells, and their potential in combinational therapy with magnetic hyperthermia. Magnetic and structural characterisation found all dopings of nanoparticles (NPs) to be pure and single phase with an average crystallite size of approximately 15 nm for undoped NPs and 20 nm for silver doped NPs. Additionally, neutron diffraction reveals that La0.9Ag0.1MnO3 (10%-LAGMO) NPs exhibit residual ferromagnetism at 300 K that is not present in lower doped NPs studied in this work, indicating that the Curie temperature may be manipulated according to silver doping. This radiobiological study reveals a completely cancer-cell selective treatment for LaMnO3, La0.975Ag0.025MnO3 and La0.95Ag0.05MnO3 (0, 2.5 and 5%-LAGMO) and also uncovers a potent combination of undoped lanthanum manganite with orthovoltage radiation. Cell viability assays and real time imaging results indicated that a concentration of 50 µg/mL of the aforementioned nanoparticles do not affect the growth of Madin-Darby Canine Kidney (MDCK) non-cancerous cells over time, but stimulate its metabolism for overgrowth, while being highly toxic to 9L gliosarcoma (9LGS). This is not the case for 10%-LAGMO nanoparticles, which were toxic to both non-cancerous and cancer cell lines. The nanoparticles also exhibited a level of toxicity that was regulated by the overproduction of free radicals, such as reactive oxygen species, amplified when silver ions are involved. With the aid of fluorescent imaging, the drastic effects of these reactive oxygen species were visualised, where nucleus cleavage (an apoptotic indicator) was identified as a major consequence. The genotoxic response of this effect for 9LGS and MDCK due to 10%-LAGMO NPs indicates that it is also causing DNA double strand breaks within the cell nucleus. Using 125 kVp orthovoltage radiation, in combination with an appropriate amount of NP-induced cell death, identified undoped lanthanum manganite as the most ideal treatment. Real-time imaging following the combination treatment of undoped lanthanum manganite nanoparticles and radiation, highlighted a hinderance of growth for 9LGS, while MDCK growth was boosted. The clonogenic assay following incubation with undoped lanthanum manganite nanoparticles combined with a relatively low dose of radiation (2 Gy) decreased the surviving fraction to an exceptionally low (0.6 ± 6.7)%. To our knowledge, these results present the first biological in-depth analysis on silver-doped lanthanum manganite as a brain cancer selective chemotherapeutic and radiation dose enhancer and as a result will propel its first in vivo investigation.
Assuntos
Nanopartículas Metálicas , Prata , Animais , Cães , Lantânio/toxicidade , Compostos de Manganês , Nanopartículas Metálicas/toxicidadeRESUMO
Due to the wide application of rare-earth elements (REEs) in the last decades, lanthanum has increasingly entered the environment and has gradually accumulated in the human body through the food chain. Lanthanum is worth paying attention in terms of food safety. Although the genotoxicity of lanthanum has been studied in vitro, data on its DNA damage in vivo rodent are limited, moreover, which have also presented some controversy. This study aimed to conduct an in vivo rodent alkaline comet assay, and as a companion test to the lanthanum nitrate carcinogenicity test. We conducted an oral gavage experiment for 180 days (26 weeks) to test for the persistence of DNA damage of long-term low-dose accumulation of lanthanum nitrate (12.5, 25, and 50 mg/kg body weight), in F1 hybrid C57-ras transgenic mice (CB6F1) by using alkaline comet assay in the blood and liver. The comet assay revealed that all the tested concentrations of lanthanum nitrate did not induce DNA damage in any of the tissues investigated, whereas DNA damage was induced in the positive control group. These results could indicate that lanthanum nitrate can accumulate in tissues and organs of the mice after exposure, and does not possess DNA damage in C57-ras transgenic mice after repeated treatments at oral doses up to 50 mg/kg·BW for 26 weeks; also, it did not cause pathological changes in the liver of the mice.
Assuntos
Dano ao DNA , Lantânio , Animais , Ensaio Cometa , Humanos , Lantânio/toxicidade , Camundongos , Camundongos TransgênicosRESUMO
With the widespread application of rare earth elements (REEs) in environment safety, food and medicine, they accumulate in the ecosystem and different human organs where REEs exert certain biological effects. Low dose REEs are proved to perform antioxidant effects, while high concentration can cause oxidative stress. However, scant information about rational doses and underlying mechanism of REEs as oxidants/antioxidants were illustrated. To elucidate these problems, here we performed a study that the ICR mice were received 0.1, 0.2, 1.0, 2.0 and 20.0 mg/kg lanthanum nitrate (La(NO3)3) by gavage for 30 days, and then were given 12 mL/kg ethanol once to undergo acute ethanol-induced oxidative stress. The antioxidant enzymes, antioxidants, peroxides and related proteins in Keap 1/Nrf2/p62 signaling pathway were measured. The results showed that La(NO3)3 inhibited hepatic morphological alternations by histopathological examination. Meanwhile, elevated superoxide dismutase (SOD) and glutathione (GSH), coupled with decreased alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA) and protein carbonyl (PC) were observed in serum and liver tissues of mice by enzyme-linked immunosorbent assay test. Furthermore, western blot analysis demonstrated that oxidative stress was alleviated due to enhanced NF-E2-related factor 2 (Nrf2) and phosphorylated p62 expressions as well as lower Kelch-like ECH-associated protein-1 (Keap 1), followed by the activation of heme oxygenase 1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO-1) and glutamate cysteine ligase, catalytic (GCLC) proteins. Our findings clearly highlighted that La(NO3)3 could restore the redox homeostasis disrupted by ethanol through provoking Keap 1/Nrf2/p62 signaling pathway, and the optimal dosages were 1.0 and 2.0 mg/kg.
Assuntos
Lantânio , Fator 2 Relacionado a NF-E2 , Animais , Antioxidantes , Ecossistema , Etanol , Lantânio/toxicidade , Camundongos , Camundongos Endogâmicos ICR , Fator 2 Relacionado a NF-E2/metabolismo , Oxirredução , Estresse OxidativoRESUMO
China is the world's largest rare earth producer and exporter, previous studies have shown that rare earth elements can cause oxidative damage in animal testis. However, the molecular mechanisms underlying these observations have yet to be elucidated. In this paper, male mice were fed with different doses (10, 20, and 40 mg/kg BW) of LaCl3 for 90 consecutive days, regulatory role of nuclear factor erythroid-2 related factor 2 (Nrf-2)/antioxidant response element (ARE) pathway in testicular oxidative stress induced by LaCl3 were investigated. Analysis showed that LaCl3 exposure could lead to severe testicular pathological changes and apoptosis in spermatogenic cells, it up-regulated the peroxidation of lipids, proteins and DNA, and induced the excessive levels of reactive oxygen species (ROS) production in mouse testis, reduced the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione S epoxide transferase (GST) as well as the glutathione (GSH) content. Furthermore, exposure to LaCl3 also downregulated the expression of Nrf2 and its target gene products, including heme oxygenase 1 (HO-1), glutamate-cysteine ligase catalytic subunit (GCLC), NAD(P)H dehydrogenase [quinine] 1(NQO1), protein kinase C (PKC), and phosphatidylinositol 3-kinase (PI3K), but upregulated the expression of Kelch-like ECH-related protein 1 (Keap1) in damaged mouse testes. Collectively, our data imply that the oxidative damage induced by LaCl3 in testis was related to inhibition of the Nrf-2/AREs pathway activation.
Assuntos
Lantânio/toxicidade , Estresse Oxidativo/fisiologia , Animais , Elementos de Resposta Antioxidante , Apoptose , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Heme Oxigenase-1/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Masculino , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Testículo/metabolismoRESUMO
Lanthanum oxide nanoparticles (La2O3 NPs) are used in photoelectric and catalytic applications. Astaxanthin (ASX) is a red carotenoid pigment with antioxidant and anti-inflammatory properties, and the antioxidant activities promote neuroprotection. This study explored the effect of ASX supplementation on La2O3 NP-induced neurotoxicity in mice and the molecular mechanisms of such protective effects. Amongst our findings, we determined that ASX treatment significantly attenuated La2O3 NP-induced behavioural abnormalities, histopathological evidence of hippocampal injury and ultrastructural changes in the CA1 region of the hippocampus. ASX treatment also markedly inhibited the production of ROS and activated PI3K/AKT signaling, which facilitated the nuclear translocation of Nrf-2 and reversed the down-regulation of HO-1, NQO1 and GCLM proteins in the hippocampus that were induced by sub-chronic exposure to La2O3 NPs. Administration of ASX to mice receiving La2O3 NPs also resulted in decreased expression of iNOS, IL-1ß, TNF-α, COX-2, Bax and Caspase-3 and in increased expression of BDNF, NGF and Bcl-2 observed in response to La2O3 NPs. In conclusion, ASX had a markedly protective effect against the negative sequelae associated with La2O3 NP-induced neurotoxicity. This may result from the activation of the PI3K/AKT/Nrf-2 signaling and via the inhibition of oxidative stress, neuroinflammation and cellular apoptosis.
Assuntos
Lantânio/toxicidade , Nanopartículas Metálicas/toxicidade , Síndromes Neurotóxicas/prevenção & controle , Óxidos/toxicidade , Transdução de Sinais/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Xantofilas/farmacologiaRESUMO
BACKGROUND: Lanthanum (La) exposure can cause central nervous system (CNS) damage and dysfunction in children, seriously affecting intellectual development. miR-124 plays an important role in the development of the nervous system. We exposed rats to a La environment then observed the rats' learning and memory damage and neurotoxicity and the relationship with miR-124. METHODS: Rats were exposed to LaCl3 via drinking water. The rats' offspring were exposed to LaCl3 from their mother before weaning, then from La water for 28 days. A Morris water maze was used to observe spatial memory capabilities. H&E staining and TUNEL assays were used to observe pathological changes and apoptosis in the hippocampus. miR-124 was detected by RT-qPCR, and its targeting was confirmed by luciferase assay. The HT22 cell line was cultured with LaCl3 and treated with miR-124 mimics or inhibitors; then, expression of PI3K/Akt-related proteins was detected by western blot. RESULTS: La exposure can lead to impaired learning and memory ability in offspring. Offspring with La accumulations in the hippocampus showed severe damage, disordered cells, and increased neurocyte apoptosis. In vitro, the postsynaptic density protein 95 was downregulated under La exposure and apoptosis increased. This effect of La can be attenuated by miR-124 inhibitors and enhanced by miR-124 mimics. LaCl3 exposure increased miR-124 expression and targeting on PIK3CA, downregulating PI3K, p-Akt, and p-NF-κB p65. CONCLUSION: La causes neurotoxicity by upregulating miR-124 expression and targeting PIK3CA through the PI3K/Akt signaling pathway.
Assuntos
Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Lantânio/toxicidade , MicroRNAs , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Feminino , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , MicroRNAs/genética , MicroRNAs/metabolismo , Neurotoxinas/toxicidade , Ratos , Ratos Wistar , Memória Espacial/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacosRESUMO
This study investigated the influences of lanthanum (La) exposure on learning and memory and the expression of apoptosis-related proteins in offspring rats. Wistar female rats were randomly divided into a control group (NC) and 0.25%, 0.5% and 1.0% LaCl3 treatment groups, with eight per group. La dye was transmitted to offspring rats through parental blood circulation and breast milk before delactation and through water drinking after delectation. Offspring rats were killed at 14, 28 and 42 days after birth. Hippocampal neurons were observed by microscope, and apoptosis and necrosis were tested. The expression levels of apoptosis-related proteins were detected by Western blot, and Morris water maze experiments were used to measure learning and memory abilities. LaCl3 groups showed longer escape latency periods and swimming distances than the NC group (p < 0.05). The 1.0% LaCl3 group passed across the target quadrants and platforms more times and stayed in the target quadrants for less time, than the NC group (p < 0.05). At 42 days, the apoptosis rate and necrosis in the hippocampus of the 1.0% LaCl3 group were significantly higher than those of other groups. There was a significant difference among LaCl3 groups in terms of protein expressions measured in the hippocampus. In LaCl3 groups, caspase-3 and caspase-9 were significantly higher than in the NC group (p < 0.05). Therefore, La exposure can promote neuronal apoptosis by regulating the protein expressions of Akt, Bcl-2, Bcl-xl, Bax, Bad, caspase-3 and caspase-9, thus damaging learning and memory and the hippocampal neurons of offspring rats.
Assuntos
Apoptose/efeitos dos fármacos , Lantânio/toxicidade , Memória/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos , Animais , Caspase 3/efeitos dos fármacos , Caspase 3/metabolismo , Caspase 9/efeitos dos fármacos , Caspase 9/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Aprendizagem/efeitos dos fármacos , Neurônios/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteína X Associada a bcl-2/efeitos dos fármacos , Proteína X Associada a bcl-2/metabolismo , Proteína de Morte Celular Associada a bcl/efeitos dos fármacos , Proteína de Morte Celular Associada a bcl/metabolismo , Proteína bcl-X/efeitos dos fármacos , Proteína bcl-X/metabolismoRESUMO
The rare earth elements are widely used in agricultural and light industry development. They promote the growth of crop seedlings, enhance root development and change the metal properties. Due to the large amount of rare earth minerals mined in China, rare earth elements have been detected in both coastal and estuary areas. They cause pollution and threaten the health of aquatic organisms and human beings. This study investigates the effects of lanthanum on two marine bait algae, and analyzes the changes in the photosynthetic and antioxidant systems of the two algae. The results show that rare earth elements have significant inhibitory effects upon the two algae. The OJIP kinetic curve value decreases with an increasing concentration of La(NO3)3 ·6H2O. The parameters of the fluorescence value were analyzed. The ABS/RC increases and the DI0/RC decreases during the first 24 h after exposure. The effects on the photosynthetic and antioxidant systems at low concentrations (both EC10 and EC20) show that the TR0/ABS increases, and the ET0/RC, ABS/RC, and DI0/RC has a decreasing trend after 30 min. However, after 24 h, normal levels were restored. In addition, the study finds that the TR0/ABS increases after 24 h, leading to an increase in reactive oxygen species. The antioxidant system analysis also confirms the increase in the activities of antioxidant enzymes, such as SOD and GSH. The experiment is expected to support the marine pollution of rare earths and the theoretical data of the impact on marine primary producers.
Assuntos
Chlorella vulgaris/efeitos dos fármacos , Diatomáceas/efeitos dos fármacos , Lantânio/toxicidade , Poluentes Químicos da Água/toxicidade , Chlorella vulgaris/metabolismo , Diatomáceas/metabolismo , Glutationa/metabolismo , Fotossíntese/efeitos dos fármacos , Complexo de Proteína do Fotossistema II/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismoRESUMO
Multiple contaminants can affect plant-microbial remediation processes because of their interactive effects on environmental behaviour, bioavailability and plant growth. Recent studies have suggested that arbuscular mycorrhizal fungi (AMF) can facilitate the revegetation of soils co-contaminated with rare earth elements (REEs) and heavy metals. However, little is known regarding the role of AMF in the interaction of REEs and heavy metals. A pot experiment was conducted to evaluate the effects of Claroideoglomus etunicatum on the biomass, nutrient uptake, metal uptake and translocation of maize grown in soils spiked with Lanthanum (La) and Cadmium (Cd). The results indicated that individual and combined applications of La (100â¯mgâ¯kg-1) and Cd (5â¯mgâ¯kg-1) significantly decreased root colonization rates by 22.0%-35.0%. With AMF inoculation, dual-metal treatment significantly increased maize biomass by 26.2% compared to single-metal treatment. Dual-metal treatment significantly increased N, P and K uptake by 20.1%-76.8% compared to single-metal treatment. Dual-metal treatment significantly decreased shoot La concentration by 52.9% compared to single La treatment, whereas AM symbiosis caused a greater decrease of 87.8%. Dual-metal treatment significantly increased shoot and root Cd concentrations by 65.5% and 58.7% compared to single Cd treatment and the La translocation rate by 142.0% compared to single La treatment, whereas no difference was observed between their corresponding treatments with AMF inoculation. Furthermore, AMF had differential effects on the interaction of La and Cd on metal uptake and translocation under the background concentrations of soil metals. Taken together, these results indicated that AMF significantly affected the interaction between La and Cd, depending on metal types and concentrations in soils. These findings promote a further understanding of the contributions of AMF to the phytoremediation of co-contaminated soil.
Assuntos
Cádmio/análise , Lantânio/análise , Micorrizas/efeitos dos fármacos , Poluentes do Solo/toxicidade , Zea mays/microbiologia , Biodegradação Ambiental , Biomassa , Cádmio/toxicidade , Glomeromycota , Lantânio/toxicidade , Metais Pesados/análise , Micorrizas/química , Micorrizas/fisiologia , Desenvolvimento Vegetal , Raízes de Plantas/efeitos dos fármacos , Plântula/química , Solo/química , Microbiologia do Solo , Poluentes do Solo/análise , Simbiose/efeitos dos fármacos , Zea mays/crescimento & desenvolvimentoRESUMO
Rare earths have been widely used in a huge number of areas in industry and medicine. Therefore, they exist in the environment and possibly accumulated within the human body. However their effects in the living organism particularly in the female reproductive system are still unclear. In this work, the subcellular behavior of lanthanum and cerium was investigated through the Transmission Electron Microscopy (TEM), in different territories of the reproductive system of Wistar rats exposed intraperitoneally to soluble solution of these elements during 2 weeks. Ultrastructural investigations of ultrathin sections from uterus and ovary of treated rats revealed the existence of inclusions with high electron density and heterogeneous aspects in the lysosomes of uterus and ovary cells. Many disruptions of architecture were observed, accompanied with several changes like vacuolations, significant expansion of the endoplasmic reticulum, mitochondrial alterations and necrotic cells, demonstrating the toxicity of these elements with doses used. Phagolysosomes as well as eosinophils were also seen. Our experimental investigations revealed no intralysosomal inclusions in ultrathin sections of the uterus and ovary of pregnant control females. The original mechanism implicated in this insolubilization-concentration phenomenon of these elements, as non-soluble phosphate form, in the lysosomes is a biochemical one involving intralysosomal hydrolytic enzymes, the acid phosphatase.
Assuntos
Cério/toxicidade , Lantânio/toxicidade , Ovário/ultraestrutura , Útero/ultraestrutura , Animais , Cério/administração & dosagem , Endométrio/efeitos dos fármacos , Endométrio/ultraestrutura , Feminino , Células da Granulosa/efeitos dos fármacos , Células da Granulosa/ultraestrutura , Injeções Intraperitoneais , Lantânio/administração & dosagem , Miométrio/efeitos dos fármacos , Miométrio/ultraestrutura , Ovário/efeitos dos fármacos , Ratos Wistar , Soluções , Útero/efeitos dos fármacosRESUMO
Lanthanum (La) exposure can lead to learning and memory disorder in animals; however, the underlying mechanism of La induced neurotoxicity is still unknown. It has been demonstrated that Nrf2 activation by tert-butylhydroquinone (tBHQ) results in neuroprotection against brain injuries. However, little study has been done with respect to its effect on La induced neurotoxicity. Herein, experiments are undertaken to determine if there is a correlation between La damaged astrocytes and the Nrf2/ARE signalling pathway. Primary rat astrocytes are exposed to 0 mmol L-1, 0.125 mmol L-1, 0.25 mmol L-1 and 0.5 mmol L-1 lanthanum chloride (LaCl3) for 24 hours. The results reveal that LaCl3 increases the apoptosis/necrosis rate of astrocytes, decreases the glutathione (GSH) content, increases reactive oxygen species (ROS) levels and significantly down-regulates Nrf2 as well as the mRNA and protein expression of Nrf2-regulated genes, including NADP(H): dehydrogenase quinone 1 (NQO1), hemeoxygenase-1 (HO-1), superoxide dismutase 2 (SOD2), glutathione peroxidase 1 (GSH-Px1), glutathione-s-transferase (GST) and γ-glutamine cysteine synthase (γ-GCS) in astrocytes. In addition, it is found that tBHQ displays an antagonistic effect on astrocytes damaged by LaCl3. Therefore, La damaged astrocytes are possibly related to the down-regulated Nrf2/ARE pathway, and treatment with tBHQ clearly activates the Nrf2/ARE signalling pathway, which exerts protection against oxidative stress.
Assuntos
Astrócitos/efeitos dos fármacos , Hidrolases de Éster Carboxílico/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Hidroquinonas/farmacologia , Lantânio/toxicidade , Fator 2 Relacionado a NF-E2/metabolismo , Fármacos Neuroprotetores/farmacologia , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Astrócitos/metabolismo , Astrócitos/patologia , Células Cultivadas , Ratos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
Lanthanum exerts adverse effects on the central nervous system. However, the mechanism underlying these adverse effects has not been clarified. It is known that oxidative stress plays an important role in neurological injuries induced by harmful factors. Nuclear factor erythroid 2-related factor (Nrf2) is very important in the response to oxidative stress in tissues and cells. The purpose of this study was to explore the effect of lanthanum chloride (LaCl3 ) on the spatial learning and memory of rats and to determine whether the Nrf2/antioxidant response element pathway acts in the hippocampus. Four groups of Wistar rats were exposed to 0 mM, 9 mM, 18 mM or 36 mM LaCl3 through their drinking water from the day of birth to 2 months after weaning. The results showed that LaCl3 impaired the spatial learning and memory of the rats, damaged the neuronal ultrastructure, increased reactive oxygen species levels and significantly down-regulated Nrf2 as well as the mRNA and protein expression of Nrf2-regulated genes, including NADP(H): dehydrogenase quinone 1, haeme oxygenase-1, superoxide dismutase 2, glutathione peroxidase 1, glutathione-S-transferase, γ-glutamine cysteine synthase and glutathione reductase, in the hippocampus. This study suggests that LaCl3 can impair the spatial learning and memory of rats, possibly by perturbing the Nrf2/antioxidant response element signalling pathway.
Assuntos
Elementos de Resposta Antioxidante/fisiologia , Lantânio/toxicidade , Aprendizagem em Labirinto/fisiologia , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Animais , Elementos de Resposta Antioxidante/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Relação Dose-Resposta a Droga , Feminino , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/antagonistas & inibidores , Distribuição Aleatória , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologiaRESUMO
Cobalt monoxide (CoO) and lanthanum oxide (La2O3) nanoparticles are 2 metal oxide nanoparticles with different redox potentials according to their semiconductor properties. By utilizing these two nanoparticles, this study sought to determine how metal oxide nanoparticle's mode of toxicological action is related to their physio-chemical properties in human small airway epithelial cells (SAEC). We investigated cellular toxicity, production of superoxide radicals and alterations in gene expression related to oxidative stress, and cellular death at 6 and 24 h following exposure to CoO and La2O3(administered doses: 0, 5, 25, and 50 µg/ml) nanoparticles. CoO nanoparticles induced gene expression related to oxidative stress at 6 h. After characterizing the nanoparticles, transmission electron microscope analysis showed SAEC engulfed CoO and La2O3nanoparticles. CoO nanoparticles were toxic after 6 and 24 h of exposure to 25.0 and 50.0 µg/ml administered doses, whereas, La2O3nanoparticles were toxic only after 24 h using the same administered doses. Based upon the Volumetric Centrifugation Methodin vivoSedimentation, Diffusion, and Dosimetry, the dose of CoO and La2O3nanoparticles delivered at 6 and 24 h were determined to be: CoO: 1.25, 6.25, and 12.5 µg/ml; La2O3: 5, 25, and 50 µg/ml and CoO: 4, 20, and 40 µg/ml; and La2O3: 5, 25, 50 µg/ml, respectively. CoO nanoparticles produced more superoxide radicals and caused greater stimulation of total tyrosine and threonine phosphorylation at both 6 and 24 h when compared with La2O3nanoparticles. Taken together, these data provide evidence that different toxicological modes of action were involved in CoO and La2O3metal oxide nanoparticle-induced cellular toxicity.
Assuntos
Cobalto/toxicidade , Células Epiteliais/efeitos dos fármacos , Lantânio/toxicidade , Nanopartículas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Óxidos/toxicidade , Mucosa Respiratória , Técnicas de Cultura de Células , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cobalto/química , Relação Dose-Resposta a Droga , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Expressão Gênica/efeitos dos fármacos , Humanos , Lantânio/química , Microscopia Eletrônica de Transmissão , Nanopartículas/química , Estresse Oxidativo/genética , Óxidos/química , Espécies Reativas de Oxigênio/metabolismo , Mucosa Respiratória/citologia , Mucosa Respiratória/efeitos dos fármacos , Propriedades de SuperfícieRESUMO
A great deal of literature is available regarding the environmental and ecological effects of rare earth element pollution on plants. These studies have shown that excess lanthanum (La) (III) in the environment can inhibit plant growth and even cause plant death. Moreover, inhibition of plant photosynthesis is known to be one of the physiological bases of these damages. However, the mechanism responsible for these effects is still unclear. In this study, the mechanism of La(III)-induced damage to plant photosynthesis was clarified from the viewpoint of the chloroplast ultrastructure, the contents of chloroplast mineral elements and chlorophyll, the transcription of chloroplast ATPase subunits and chloroplast Mg(2+)-ATPase activity, in which rice was selected as a study object. Following treatment with low level of La(III), the chloroplast ultrastructure of rice was not changed, and the contents of chloroplast mineral elements (Mg, P, K, Ca, Mn, Fe, Ni, Cu, and Zn) increased, but the chlorophyll content did not change significantly. Moreover, the transcription of chloroplast ATPase subunits, chloroplast Mg(2+)-ATPase activity, the net photosynthetic rate and growth indices increased. Following treatment with high levels of La(III), the chloroplast ultrastructure was damaged, chloroplast mineral elements (except Cu and Zn) and chlorophyll contents decreased, and the transcription of chloroplast ATPase subunits, chloroplast Mg(2+)-ATPase activity, the net photosynthetic rate and growth indices decreased. Based on these results, a possible mechanism of La(III)-induced damage to plant photosynthesis was proposed to provide a reference for scientific evaluation of the potential ecological risk of rare earth elements in the environment.
Assuntos
Cloroplastos/efeitos dos fármacos , Lantânio/toxicidade , Fotossíntese/efeitos dos fármacos , Poluentes do Solo/toxicidade , Adenosina Trifosfatases/metabolismo , Clorofila/metabolismo , Cloroplastos/metabolismo , Cloroplastos/ultraestrutura , Microscopia Eletrônica de Transmissão , Oryza/efeitos dos fármacos , Oryza/metabolismoRESUMO
We investigated the phytoremediation potential of Elodea nuttallii to remove rare earth metals from contaminated water. The laboratory experiments were designed to assess the responses induced by lanthanum (5-20mgL(-1)) in E. nuttallii over a period of 7 days. The results showed that most La (approximately 85%) was associated with the cell wall. The addition of La to the culture medium reduced the concentration of K, Ca, Cu, Mg, and Mn. However, O2(·-) levels increased with a concomitant increase in the malondialdehyde (MDA) concentration as the La concentration increased, which indicated that the cells were under oxidative stress. Significant reductions in the levels of chlorophyll (Chl) a, b, and carotenoids (Car) were observed in a concentration-dependent manner. However, the levels of reduced glutathione (GSH), total non-protein thiols (TNP-SH) and phytochelatins (PCs) increased for all La concentrations. The results suggested that La was toxic to E. nuttallii because it induced oxidative stress and disturbed mineral uptake. However, E. nuttallii was able to combat La induced damage via an immobilization mechanism, which involved the cell wall and the activation of non-enzymatic antioxidant.
Assuntos
Hydrocharitaceae/metabolismo , Lantânio/metabolismo , Poluentes Químicos da Água/metabolismo , Antioxidantes/metabolismo , Biodegradação Ambiental , Carotenoides/metabolismo , Clorofila/metabolismo , Clorofila A , Glutationa/metabolismo , Hydrocharitaceae/efeitos dos fármacos , Lantânio/toxicidade , Malondialdeído/metabolismo , Oxirredução , Estresse Oxidativo , Fitoquelatinas/metabolismo , Poluentes Químicos da Água/toxicidadeRESUMO
Physiology, oxidative stress and production of metabolites in Hypericum perforatum exposed to moderate Cd and/or La concentration (10 µM) were studied. La evoked increase in reactive oxygen species, malondialdehyde and proline but suppressed growth, tissue water content, glutathione, ascorbic acid and affected mineral nutrient contents more than Cd while the impact of Cd+La was not synergistic. Similar trend was observed at the level of superoxide dismutase gene expression. Shoot Cd amount increased in Cd+La while only root La increased in the same treatment. Extensive quantification of secondary metabolites revealed that La affected phenolic acids more pronouncedly than Cd in shoots and roots. Flavonols were suppressed by La that could contribute to the appearance of oxidative damage. Procyanidins increased in response to La in the shoots but decreased in the roots. Metabolic responses in Cd+La treatment resembled those of La treatment (almost identically in the roots). Phenylalanine ammonia-lyase activity was mainly suppressed by La. The presence of La also depleted amount of hypericin and expression of its putative gene (hyp-1) showed similar trend but accumulation of hyperforin increased under Cd or La excess. Clear differences in the stem and root anatomy in response to Cd or La were also found. Overall, H. perforatum is La-sensitive species and rather Cd ameliorated negative impact of La.
Assuntos
Cádmio/toxicidade , Poluentes Ambientais/toxicidade , Hypericum/metabolismo , Lantânio/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Biomassa , Flavonoides/metabolismo , Hidroxibenzoatos/metabolismo , Hypericum/efeitos dos fármacos , Hypericum/crescimento & desenvolvimento , Microscopia de Fluorescência , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Plântula/efeitos dos fármacos , Plântula/crescimento & desenvolvimento , Plântula/metabolismoRESUMO
Exposure to lanthanoids (Ln) elicits an adverse response such as oxidative injury of lung in animals and human. The molecular targets of Ln remain unclear. In the present study, the function and signal pathway of nuclear factor erythroid 2 related factor 2 (Nrf2) in LaCl3 -induced oxidative stress in mouse lung were investigated. Mice were exposed to 2, 5, and 10 mg/kg body weight by nasal administration for 6 consecutive months. With increased doses, La was markedly accumulated and promoted the reactive oxygen species (ROS) production in the lung, which in turn resulted in peroxidation of lipids, proteins and DNA, and severe pulmonary damages. Furthermore, LaCl3 exposure could significantly increase levels of Nrf2, heme oxygenase 1 (HO-1) and glutamate-cysteine ligase catalytic subunit (GCLC) expressions in the LaCl3 -exposed lung. These findings imply that the induction of Nrf2 expression is an adaptive intracellular response to LaCl3 -induced oxidative stress in mouse lung, and that Nrf2 may regulate the LaCl3 -induced pulmonary damages.