RESUMEN
Xylans are present naturally in various plants and have important uses in nutrition, food, novel material and biotechnology; however, to date, data regarding their systemic toxicity and safety evaluation is still limited. This study investigated the potential toxicity of xylan from sugarcane bagasse by a subchronic toxicity study in rats. A total of 80 male and female rats were fed with diets containing 10%, 5%, 2.5% and 0% (control) xylan for 90 days. A toxicological assessment was performed including mortality, body and organ weights, food consumption, blood biochemistry, hematology, urinalysis, gross necropsy and histopathological examinations. There were no signs of toxicity and treatment-related changes in rats treated with xylan. The no-observed-adverse-effect levels (NOAEL) of xylan were 9.0 g kg-1 bw for males and 10.6 g kg-1 bw for females of rats under this experimental condition, respectively.
Asunto(s)
Celulosa/química , Saccharum , Xilanos/toxicidad , Administración Oral , Animales , Femenino , Masculino , Nivel sin Efectos Adversos Observados , Ratas , Ratas Sprague-Dawley , Pruebas de Toxicidad SubcrónicaRESUMEN
Epidemiological studies have shown that air pollution particulate matter (PM) is associated with increased respiratory morbidity and mortality. However, the mechanisms are not fully understood. Oxidative stress-mediated apoptosis plays an important role in the occurrence of respiratory diseases. In this study, human bronchial epithelial (16-HBE) cells were exposed to different concentrations (16-128 µg/ml) of PM(2.5) for 24 h to investigate the apoptosis induced by PM(2.5). The results showed that PM(2.5) exposure significantly induced apoptosis, DNA strand breaks, and oxidative damage in a dose-dependent manner in 16-HBE cells. The expression of p53 and p73 increased significantly along with the dose of PM(2.5) in 16-HBE cells, whereas the expression of p21(Cip1/WAF1) decreased; the expression of mdm2 increased and then decreased, but not significantly. Taken together, these observations indicate that PM(2.5) may lead to oxidative damage and induce apoptosis through the p53-dependent pathway in 16-HBE cells. p53-Dependent apoptosis mediated by DNA strand breaks may be an important mechanism of PM(2.5)-induced apoptosis in 16-HBE cells.
Asunto(s)
Contaminación del Aire/efectos adversos , Apoptosis/efectos de los fármacos , Bronquios/efectos de los fármacos , Material Particulado/toxicidad , Mucosa Respiratoria/efectos de los fármacos , Proteína p53 Supresora de Tumor/agonistas , Salud Urbana , Bronquios/metabolismo , Línea Celular , China , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/antagonistas & inhibidores , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Roturas del ADN , Proteínas de Unión al ADN/agonistas , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Monitoreo del Ambiente , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Cinética , Proteínas Nucleares/agonistas , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Concentración Osmolar , Estrés Oxidativo/efectos de los fármacos , Proteínas Proto-Oncogénicas c-mdm2/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-mdm2/química , Proteínas Proto-Oncogénicas c-mdm2/genética , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Características de la Residencia , Mucosa Respiratoria/metabolismo , Proteína Tumoral p73 , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Proteínas Supresoras de Tumor/agonistas , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismoRESUMEN
Manganese (Mn) is an essential micronutrient in maintaining homeostasis in the human body, while excessive Mn exposure can lead to neurological disorders. To investigate whether there is an association between elevated ROS and pyroptosis caused by Mn exposure using both in vitro and in vivo models. We exposed BV2 and N2a, which represent microglial cells and Neuroblastoma cells in the brain, respectively, to different concentrations of Mn for 24 h. Following Mn exposure, we assessed cell morphology, levels of lactate dehydrogenase, and cellular ROS levels. C57BL/6 male mice were exposed to 0-100 mg/kg MnCl2·4H2O for 12 weeks through gavage. The expression level of pyroptosis proteins including caspase3 and GSDME in the hippocampus was examined. We found that Mn exposure resulted in elevated levels of cellular ROS and protein expression of Caspase3 and GSDME in both N2a and BV2 cells. The pyroptosis levels were blunted by either inhibiting Caspase3 expression or ROS production. In the in vivo model, protein levels of Caspase3 and GSDME also increased dependent of Mn concentrations. These findings suggested that neuronal pyroptosis induced by Mn exposure may occur through the ROS-stimulated Caspase3-GSDME pathway. Moreover, utilizing inhibitors targeting Caspase3 or ROS may provide protection against Mn-induced toxicity.
Asunto(s)
Manganeso , Piroptosis , Ratones , Animales , Masculino , Humanos , Manganeso/toxicidad , Especies Reactivas de Oxígeno/metabolismo , Caspasa 3/genética , Caspasa 3/metabolismo , Ratones Endogámicos C57BL , Transducción de SeñalRESUMEN
Excessive environmental exposure to manganese (Mn) has been linked to cognitive impairments, circular RNAs (circRNAs) have been recognized for their roles in epigenetic regulation in various biological processes, including neurological pathogenesis. Previous studies found that ferroptosis, an iron ion-dependent programmed cell death, may be involved in cognitive impairments. However, specific mechanisms underlying the relationship among circRNA, ferroptosis, and neurotoxicity of Mn are not well-understood. In the current study, RNA sequencing was performed to profile RNA expression in Neuro-2a (N2a) cells that were treated with 300 µM Mn. The potential molecular mechanisms of circHmbox1(3,4) in Mn-induced cognitive impairments were investigated via various experiments, such as Western blot and intracerebroventricular injection in mice. We observed a significant decrease in the expression of circHmbox1(3,4) both in vitro and in vivo following Mn treatment. The results of Y maze test and Morris water maze test demonstrated an improvement in learning and memory abilities following circHmbox1(3,4) overexpression in Mn treated mice. Mn treatment may reduce circHmbox1(3,4) biogenesis through lowered expression of E2F1/QKI. Inhibiting circHmbox1(3,4) expression led to GPX4 protein degradation through protein ligation and ubiquitination. Overall, the current study showed that Mn exposure-induced cognitive dysfunction may be mediated through ferroptosis regulated by circHmbox1(3,4).
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Disfunción Cognitiva , Ferroptosis , Manganeso , ARN Circular , Animales , Ferroptosis/efectos de los fármacos , Manganeso/toxicidad , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/genética , ARN Circular/genética , Masculino , Ratones , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Fosfolípido Hidroperóxido Glutatión Peroxidasa/genética , Ratones Endogámicos C57BL , Línea Celular Tumoral , Aprendizaje por Laberinto/efectos de los fármacosRESUMEN
The reduction of agricultural emission plays an important role in realizing the dual-carbon goals. It is thus of great significance to examine the characteristics and drivers of regional agricultural carbon emission. We measured agricultural carbon emission in Jiangxi Province from the perspective of input-output and production processes, and explored the drivers and decoupling dynamics of agricultural carbon emission by using the LMDI decomposition method together with the Tapio decoupling model modified by time-varying parameter C-D production function. The results showed that agricultural carbon emission in Jiangxi increased by 26.4% from 2010 to 2021, and the carbon emission intensity decreased year by year with an average annual rate of 4.9%. Factors such as agricultural carbon intensity, labor input, and capital stock collectively reduced carbon emission by a total of 61.05 Mt, with a contribution of 27.0%, 44.5% and 28.5%, respectively. Level of agricultural economic development, agricultural structure, and technological progress had strong driving effects, which accounted for 75.7%, 5.6% and 18.8%, respectively. Agricultural carbon emission in Jiangxi was weakly decoupled from economic development, capital stock, and technological progress factors, but was negatively decoupled from labor input. Moreover, the decoupling state was more desirable in the later period than in the earlier period. Our results suggested that the application of the time-varying parameter C-D production function is innovative and applicable by incorporating technology, labor, and capital factors in the examination of carbon emission drivers and decoupling effects.
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Carbono , Desarrollo Económico , Carbono/análisis , Agricultura , Dióxido de Carbono/análisis , ChinaRESUMEN
INTRODUCTION: A combination of zidovudine (AZT), lamivudine (3TC) and lopinavir/ritonavir (LPV/r) is one of the most effective drugs for preventing mother-to-child transmission (PMTCT) of HIV. However, limited information is available regarding its systemic toxicity. This study aimed to investigate its potential toxicity. METHOD: An acute oral toxicity test was conducted to assess the potential acute toxicity of AZT + 3TC + LPV/r. Bacterial reverse mutation, mammalian erythrocyte micronucleus and mouse spermatogonia chromosomal aberration tests were conducted to assess its potential genotoxicity. A 28-day feeding test was conducted to assess the potential subacute toxicity. RESULTS: In mice, the LD50 of the AZT + 3TC + LPV/r mixture was greater than 2000 mg/kg body weight (BW). The rate of micronucleated polychromatic erythrocytes (PCEs) increased in a dose-dependent manner in mice (P < 0.01). After treatment with AZT + 3TC + LPV/r for 28 days, the BW gain of male and female rats in the high-dose group was lower than that in the control group (P < 0.05); the relative weights of the liver, kidney, spleen and brain increased (P < 0.05); and pathological abnormalities appeared in the thyroid and spleen of male and female rats in the high-dose group. The haemoglobin (HGB) and red blood cells (RBCs) count in male and female rats decreased, but the white blood cells (WBCs) and lymphocyte apoptosis rates in male and female rats in the high-dose group increased (P < 0.05). The total protein, albumin, cholesterol and blood glucose levels of male and female rats in the high-dose group were significantly decreased (P < 0.05). The alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), creatinine (Cr) and blood urea nitrogen (BUN) levels of male and female rats in the medium- and high-dose groups increased significantly (P < 0.05). CONCLUSION: The results suggest that AZT + 3TC + LPV/r may exhibit genotoxicity and subacute toxicity under experimental conditions.
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Fármacos Anti-VIH , Infecciones por VIH , Femenino , Masculino , Animales , Ratones , Ratas , Lamivudine/toxicidad , Zidovudina/toxicidad , Zidovudina/uso terapéutico , Lopinavir/toxicidad , Ritonavir , Fármacos Anti-VIH/toxicidad , Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , MamíferosRESUMEN
The situations are complex and variant in the three stages of "carbon emission peak", "rapid reduction of carbon emission" and "deep decarbonization for carbon neutrality" in China's carbon neutralization roadmap. Forest carbon sequestration is an important means to achieve the goal of carbon neutralization in China. Its intertemporal allocation is a vital way to balance industrial emission reduction and forest carbon sequestration, reduce the cost of carbon neutrality, and gradually achieve the goal of carbon neutrality based on optimal cost. Based on the cost optimization allocation theory, we simulated the cost change process of three stages of carbon neutralization in China by quoting the theory of marginal carbon sequestration cost and combining with the existing domestic marginal abatement cost theory. The results showed that annual forest carbon sequestrations with the optimal cost in China was 20 million t, 775 million t and 1.982 billion t respectively in the three stages of "carbon emission peak", "rapid reduction of carbon emission" and "deep decarbonization for carbon neutrality", accounting for 1.8%, 17.5%, and 37.6% of the total emission reduction in each period. Compared with the way relying only on industrial emission reduction, forest carbon sequestration under the optimal cost design reduced the total cost by 48, 79136, and 909253 million US$ in the three stages of carbon neutralization, respectively. Due to the limited cost advantage of forest carbon sequestration, industrial emission reduction should be emphasized in the "carbon emission peak" stage. In the "rapid reduction of carbon emissions" stage, the cost advantage of forest carbon sequestration will be increasingly prominent. In the stage of "deep decarbonization for carbon neutrality", it is necessary to fully exploit the cost advantage of forest carbon sequestration to achieve the goal of "zero carbon" to avoid the risk of high costs, especially for industries with high decarbonization cost or that will never be completely decarbonized. The optimal cost design for forest carbon sequestration can save 988.437 billion US $ in carbon-neutral costs.
Asunto(s)
Secuestro de Carbono , Gases de Efecto Invernadero , Carbono/análisis , Dióxido de Carbono/análisis , China , BosquesRESUMEN
Sericin is a natural protein component of silks of silkworm and has potential utility in multiple areas such as pharmacological, cosmetics, and biotechnological industries. However, the understanding of its toxicological safety is still limited. This study evaluated the safety of water-extract sericin from silkworm (Bombyx mori) cocoons using different model approaches, including three genotoxicity studies (the bacterial reverse mutation test, the mammalian erythrocyte micronucleus test, and the mouse spermatogonia chromosomal aberration test) and a 90-day subchronic toxicity study in Sprague-Dawley (SD) rats. The results of this study showed that water-extract sericin was nonmutagenic and nongenotoxic both in vitro and in vivo. Sericin did not induce significant changes in the body and organ weight, food intake, blood hematology and serum biochemistry, urine index, and histopathology in rats. The NOAEL of sericin was determined to be 1 g/kg/day for male and female rats. These results indicated that water-extract sericin was of low toxicity in the experimental conditions of the current study and had the potential for application in food-related products.
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Bombyx/química , Sericinas/toxicidad , Administración Oral , Animales , Análisis Químico de la Sangre , Femenino , Riñón/efectos de los fármacos , Riñón/patología , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Ratones , Pruebas de Mutagenicidad , Tamaño de los Órganos/efectos de los fármacos , Ratas Sprague-Dawley , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/genética , Sericinas/administración & dosificación , Sericinas/aislamiento & purificación , Espermatogonias/efectos de los fármacos , Espermatogonias/fisiología , Pruebas de Toxicidad Subcrónica , Urinálisis , Agua/químicaRESUMEN
Manganese (Mn) is an essential trace element to humans. However, excessive Mn causes cognitive impairment resulting from injury to the central nervous system within the hippocampus. No ideal biomarker is currently available for evaluating Mn exposure and associated neurotoxicity in the body. Hence, this study used Mn levels in the serum (MnS), teeth (MnT), and hair (MnH) as biomarkers for evaluating the association between Mn exposure and cognitive impairment in Mn-treated rats. A total of 32 male Sprague-Dawley rats were randomly divided into four groups, received 0, 5, 10, and 20 mg/(kg day) of MnCl2·4H2O for 5 days a week for 18 weeks, respectively. Lifetime Mn cumulative dose (LMCD) was used to evaluate external Mn exposure. Hippocampus, serum, teeth, and hair specimens were collected from the rats for Mn determination by graphite furnace atomic absorption spectrometry. Learning and memory functions were assessed using the Morris water maze test. Results showed that chronic Mn exposure increased the hippocampus (MnHip), MnS, MnT, and MnH levels, as well as impaired learning and memory function in rats. MnHip, MnT, and MnH levels were positively correlated with LMCD (r = 0.759, r = 0.925, and r = 0.908, respectively; p < 0.05), escape latency (r = 0.862, r = 0.716, and r = 0.814, respectively; p < 0.05), and the number of platform crossings (r = -0.734, r = -0.514, and r = -0.566, respectively; p < 0.05). No association was observed between MnS levels and the number of platform crossings (r = -0.286, p > 0.05). Thus, MnT and MnH detected long-term low-dose Mn exposure. These parameters can be reliable biomarkers for Mn exposure and associated neurotoxicity in Mn-treated rats.
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Cabello/química , Manganeso/análisis , Diente/química , Animales , Biomarcadores/análisis , Trastornos del Conocimiento/inducido químicamente , Hipocampo/química , Masculino , Síndromes de Neurotoxicidad , Ratas , Ratas Sprague-Dawley , Espectrofotometría AtómicaRESUMEN
Chronic manganese exposure can produce cognitive deficits; however, the underlying mechanism remains unclear; reliable peripheral biomarker of Mn neurotoxicity have not yet been fully developed. Hence, this study aimed to investigate the mechanism of Mn-induced cognitive deficits and the potential biomarker of Mn neurotoxicity in rats. Thirty-two male Sprague Dawley rats were divided into four groups; these groups received intraperitoneal injections of 0, 5, 10 and 20 mg Mn/kg once daily, five days/week for 18 weeks. Learning and memory were assessed via Morris water maze test. Hippocampal and plasma Mn concentrations were measured through graphite furnace atomic absorption spectrometry. The levels of plasma BDNF, hippocampal BDNF, cAMP, protein kinase A, and pCREB were assessed through ELISA or Western blot. Results showed that the Mn concentrations in the hippocampus and plasma of the Mn-treated rats were higher than those of the control rats. Mn exposure impaired the learning and memory of rats. Plasma BDNF levels and hippocampal BDNF, cAMP, protein kinase A, and pCREB levels were significantly lower in the Mn-treated rats than in the control rats. Plasma BDNF levels were negatively correlated with the escape latency and the hippocampal and plasma Mn concentrations. By contrast, plasma BDNF levels were positively correlated with the number of platform crossings and the hippocampal cAMP and BDNF levels. Therefore, Mn impaired learning and memory probably by inhibiting the hippocampal cAMP signaling pathway in rats. Plasma BDNF levels may also be a potential effect biomarker of Mn neurotoxicity.