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AMPK/PPAR-γ/NF-κB axis participates in ROS-mediated apoptosis and autophagy caused by cadmium in pig liver
2022
Wang, Huan | Wang, Anqi | Wang, Xinqiao | Zeng, Xiangyin | Xing, Houjuan
The experiment was conducted to investigate the effects of Cadmium (Cd) on growth performance, blood biochemical parameters, oxidative stress, hepatocyte apoptosis and autophagy of weaned piglets. A total of 12 healthy weaned piglets were randomly assigned to the control and the Cd group, which were fed with a basal diet and the basal diet supplemented with 15 ± 0.242 mg/kg CdCl₂ for 30 d, respectively. Our results demonstrated that Cd significantly decreased final body weight, average daily feed intake (ADFI), average daily gain (ADG) and increased feed-to-gain (F/G) ratio (P < 0.05). For blood biochemical parameters, Cd treatment significantly decreased the red blood cell (RBC), hemoglobin (HGB), hematocrit (HCT), total protein, albumin, copper content and iron content (P < 0.05). In addition, liver injury was observed in the Cd-exposed group. Our results also demonstrated that Cd exposure contributed to the production of ROS, activated the AMPK/PPAR-γ/NF-κB pathway (increasing the expressions of P-AMPK/AMPK, NF-κB, I-κB-β, COX-2, and iNOS, decreasing the expressions of PPAR-γ and I-κB-α), finally induced autophagy (increasing the expressions of Beclin-1, the ratio of LC3-II/LC3-I and p62), and apoptosis (increasing the expressions of Bax, Bak, Caspase-9, and Caspase-3, decreasing the expression of Bcl-2). Overall, these findings revealed the vital role of AMPK/PPAR-γ/NF-κB pathway in Cd-induced liver apoptosis and autophagy, which provided deeper insights into a better understanding of Cd-induced hepatotoxicity.
Показать больше [+] Меньше [-]Evaluation of the genotoxic, mutagenic, and histopathological hepatic effects of polyoxyethylene amine (POEA) and glyphosate on Dendropsophus minutus tadpoles
2021
Lopes, Alice | Benvindo-Souza, Marcelino | Carvalho, Wanessa Fernandes | Nunes, Hugo Freire | de Lima, Phamella Neres | Costa, Matheus Santos | Benetti, Edson José | Guerra, Vinicius | Saboia-Morais, Simone Maria Teixeira | Santos, Carolina Emilia | Simões, Karina | Bastos, Rogério Pereira | de Melo e Silva, Daniela
Herbicides improve the productivity of a monoculture by eliminating weeds, although they may also be toxic and have negative effects on non-target organisms, such as amphibians. The present study evaluated the genotoxic, mutagenic, and histopathological hepatic responses of Dendropsophus minutus tadpoles to acute exposure (96 h) to the herbicide glyphosate (GLY, 65, 130, 260 and 520 μg/L) and the surfactant polyoxyethylene amine (POEA, 1.25, 2.5, 5 and 10 μg/L). On average, 174 % more genomic damage was observed in the tadpoles exposed to all concentrations of POEA in comparison with the control, while up to seven times more micronuclei were recorded, on average, at a concentration of 5 μg/L of POEA. All the individuals exposed to 10 μg/L of POEA died. The tadpoles exposed to GLY presented 165 % more DNA damage than the control, on average, at the highest concentrations (260 and 520 μg/L), and up to six times more micronuclei at 520 μg/L. The Erythrocyte Nuclear Abnormality test (ENA) detected a relatively high frequency of cells with lobed nuclei in the tadpoles expose to POEA at 5 μg/L and binucleated cells in those exposed to GLY at 520 μg/L. The hepatic histopathological observations revealed several types of lesions in the tadpoles exposed to both GLY and POEA. Overall, then, the results of the study indicate that both GLY and POEA have potential genotoxic, mutagenic, and hepatotoxic effects in D. minutus tadpoles. We emphasize the need for further studies to monitor the amphibian populations, such as those of D. minutus, which breed in aquatic environments associated with agricultural areas. The release of pollutants into natural habitats may have significant long-term impacts on the survival of anuran tadpoles.
Показать больше [+] Меньше [-]Low-level maternal exposure to cadmium, lead, and mercury and birth outcomes in a Swedish prospective birth-cohort
2020
Gustin, Klara | Barman, Malin | Stråvik, Mia | Levi, Michael | Englund-Ögge, Linda | Murray, Fiona | Jacobsson, Bo | Sandberg, Ann-Sofie | Sandin, Anna | Wold, Agnes E. | Vahter, Marie | Kippler, Maria
Observational studies have indicated that low-to-moderate exposure to cadmium (Cd), lead (Pb), and mercury (Hg) adversely affects birth anthropometry, but results are inconclusive. The aim of this study was to elucidate potential impact on birth anthropometry of exposure to Cd, Pb, and Hg in pregnant women, and to identify the main dietary sources. In the NICE (Nutritional impact on Immunological maturation during Childhood in relation to the Environment) birth-cohort in northern Sweden, blood and urine were collected from pregnant women in early third trimester. Cd, Pb and Hg were measured in erythrocytes (n = 584), and Cd also in urine (n = 581), by inductively coupled plasma mass spectrometry. Dietary data were collected through a semi-quantitative food frequency questionnaire administered in mid-third trimester. Birth anthropometry data were extracted from hospital records. In multivariable-adjusted spline regression models, a doubling of maternal erythrocyte Cd (median: 0.29 μg/kg) above the spline knot of 0.50 μg/kg was associated with reduced birth weight (B: −191 g; 95% CI: −315, −68) and length (−0.67 cm; −1.2, −0.14). The association with birth weight remained when the analysis was restricted to never-smokers. Likewise, a doubling of erythrocyte Hg (median 1.5 μg/kg, mainly MeHg) above 1.0 μg/kg, was associated with decreased birth weight (−59 g; −115, −3.0), and length (−0.29 cm; −0.54, −0.047). Maternal Pb (median 11 μg/kg) was unrelated to birth weight and length. Erythrocyte Cd was primarily associated with intake of plant derived foods, Pb with game meat, tea and coffee, and Hg with fish. The results indicated that low-level maternal Cd and Hg exposure were associated with poorer birth anthropometry. Further prospective studies in low-level exposed populations are warranted.
Показать больше [+] Меньше [-]In vitro toxicity of dimethyl phthalate to human erythrocytes: From the aspects of antioxidant and immune functions
2019
Li, Shixuan | Chi, Zhenxing | Li, Weiguo
In the study, the effects of dimethyl phthalate (DMP) on the antioxidant defense capacity and immune functions of human erythrocytes were experimentally explored. DMP affected the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) and the contents of glutathione (GSH) and malondialdehyde (MDA) in erythrocytes, thus impairing the function of antioxidant defense system of erythrocytes. When DMP concentration increased from 0 to 28 μmol L⁻¹, the SOD and GPX activities were increased firstly and then gradually decreased. When DMP concentration was below 20 μmol L⁻¹, the relative activity of SOD was enhanced by DMP and the effect was known as hormesis. The relative activity of GPX was also increased when the concentration of DMP was below 12 μmol L⁻¹. The CAT activity was more significantly inhibited by DMP than the activities of SOD and GPX, whereas the relative GSH content was increased by DMP. MDA levels were significantly changed after the exposure to DMP (0–24 μmol L⁻¹). The experimental results of the activity of SOD and CAT, and the content of MDA also suggested that DMP could inhibit the immune functions of red blood cells (RBCs), which were further proved by the decrease of two indicators (RBC-C₃b and RBC-IC) due to the destruction of C₃b receptor with immune adherence function on erythrocyte membrane. The study provides a deep understanding of the toxicity of DMP on erythrocytes.
Показать больше [+] Меньше [-]Species-specific transcriptomic responses in Daphnia magna exposed to a bio-plastic production intermediate
2019
Swart, Elmer | de Boer, Tjalf E. | Chen, Guangquan | Vooijs, Riet | van Gestel, Cornelis A.M. | Straalen, N. M. van | Roelofs, Dick
Hydroxymethylfurfural (HMF) is a plant-based chemical building block that could potentially substitute petroleum-based equivalents, yet ecotoxicological data of this compound is currently limited. In this study, the effects of HMF on the reproduction and survival of Daphnia magna were assessed through validated ecotoxicological tests. The mechanism of toxicity was determined by analysis of transcriptomic responses induced by exposure to different concentrations of HMF using RNA sequencing. HMF exerted toxicity to D. magna with an EC₅₀ for effects on reproduction of 17.2 mg/l. HMF exposure affected molecular pathways including sugar and polysaccharide metabolism, lipid metabolism, general stress metabolism and red blood cell metabolism, although most molecular pathways affected by HMF exposure were dose specific. Hemoglobin genes, however, responded in a sensitive and dose-related manner. No induction of genes involved in the xenobiotic metabolism or oxidative stress metabolism pathway could be observed, which contrasted earlier observations on transcriptional responses of the terrestrial model Folsomia candida exposed to the same compound in a similar dose. We found 4189 orthologue genes between D. magna and F. candida, yet only twenty-one genes of those orthologues were co-regulated in both species. The contrasting transcriptional responses to the same compound exposed at a similar dose between D. magna and F. candida indicates limited overlap in stress responses among soil and aquatic invertebrates. The dose-related expression of hemoglobin provides further support for using hemoglobin expression as a biomarker for general stress responses in daphnids.
Показать больше [+] Меньше [-]Environmentally relevant concentrations of carbamazepine induce liver histopathological changes and a gender-specific response in hepatic proteome of Chinese rare minnows (Gobiocypris rarus)
2018
Yan, Saihong | Wang, Miao | Liang, Xue-fang | Martyniuk, Christopher J. | Zha, Jinmiao | Wang, Zijian
To assess hepatotoxicity and to determine the underlying mechanisms of carbamazepine (CBZ) toxicity in fish, histopathology and the liver proteome were examined after Chinese rare minnow (Gobiocypris rarus) were exposed to 1, 10, and 100 μg/L CBZ for 28 days. Histopathological changes included disruption of spatial structure, pyknotic nuclei, cellular vacuolization and deformation of cell nuclei, in addition to marked swelling of hepatocytes in all treatment groups. Protein analysis revealed that there were gender-specific responses in rare minnow following exposure, and there were 47 proteins in females and 22 proteins in males identified as differentially abundant following CBZ treatments. Pathway analysis revealed that cellular processes affected by CBZ included apoptosis, cell differentiation, cell proliferation, and the respiratory chain, indicating impaired energy homeostasis. Noteworthy was that 15 proteins identified as different in abundance were associated with carcinogenicity. Relative mRNA levels for select transcripts were consistent with the changes of proteins N-myc downstream regulated gene (NDRG), Tropomyosin 2-Beta (TPM2) and annexin A4 (ANXA4). Protein pyruvate kinase, liver and RBC (PKLR) were increased at 1 and 100 μg/L CBZ without significant difference in transcript levels. These findings characterize molecular responses and histological changes in the liver that generate new insights into CBZ hepatotoxicity in Chinese rare minnow.
Показать больше [+] Меньше [-]VNN3, a potential novel biomarker for benzene toxicity, is involved in 1, 4-benzoquinone induced cell proliferation
2018
Sun, Pengling | Guo, Xiaoli | Chen, Yujiao | Zhang, Wei | Duan, Huawei | Gao, Ai
Benzene is widely employed in the field of production, and its toxicity on biological systems has received increasing attention. Cell proliferation is a major life characteristic of living organisms. KLF15 and NOTCH1 are mature and classical genes in cell proliferation studies, particularly in the area of tumor investigation. The aim of this study was to investigate the effect and mechanism of VNN3 on cell proliferation induced by 1,4-benzoquinone (1,4-BQ), an important metabolite of benzene, and obtain a sensitive biomarker for the hazard screening and health care of benzene exposure. Normally growing AHH-1 cells were cultured in vitro and were incubated with different concentrations of 1,4-BQ (0, 10, 20, and 40 μM) for 24 h. A CCK-8 assay was used to assess the cell viability, whereas EdU was used to detect the cell proliferation of AHH-1 cells. The expression of VNN3, KLF15 and NOTCH1 was detected by real-time PCR. Moreover, a lentiviral model was constructed in AHH-1 cells to interfere with VNN3 expression. The results showed that 1,4-BQ clearly increased the expression of VNN3. Moreover, 1,4-BQ dose-dependently inhibited cell proliferation and caused increased KLF15 expression; in contrast, the NOTCH1 expression decreased in AHH-1 cells. Furthermore, following interference with the VNN3 expression, the cell proliferation inhibition and the expression of KLF15 and NOTCH1 were rescued. To further investigate the action of VNN3 in benzene hematotoxicity, we assessed it in benzene-exposed workers. The results showed that there was a remarkable correlation between the VNN3 expression and hemogram, which included RBC, NEUT and HGB. In addition, analysis of the KLF15 and NOTCH1 expression showed that the VNN3 expression was related to cell proliferation, which was consistent with the in vitro results. In conclusion, VNN3 influences cell proliferation induced by 1,4-BQ by regulating the expression of KLF15 and NOTCH1. VNN3 may represent a potential biomarker of benzene toxicity.
Показать больше [+] Меньше [-]Double strand break repair and γ-H2AX formation in erythrocytes of medaka (Oryzias latipes) after γ-irradiation
2017
Sayed, Alaa El-Din Hamid | Igarashi, Kento | Watanabe-Asaka, Tomomi | Mitani, Hiroshi
The study of the DNA damage response in erythrocytes after γ-irradiation may provide evidence for its effectiveness as a biomarkers for genotoxic environmental stress. We previously reported various malformations in erythrocytes of medaka irradiated with10 Gy, but not in their micronuclei. In this study, we optimized an assay method for γ-H2AX and double strand breaks in erythrocytes of adult medaka fish after 15 Gy of γ-irradiation. The highest level of apoptosis and nuclear abnormalities, including in micronuclei, were recorded 4 h after γ-irradiation, as was the highest level of γ-H2AX foci in erythrocytes. These results suggest that recognition and repair processes occur as a response to DNA damage in erythrocytes in medaka.
Показать больше [+] Меньше [-]Sublethal biochemical, histopathological and genotoxicological effects of short-term exposure to ciprofloxacin in catfish Rhamdia quelen
2022
Akiyama Kitamura, Rafael Shinji | Vicentini, Maiara | Perussolo, Maiara Carolina | Lirola, Juliana Roratto | Cirilo dos Santos, Camilla Freitas | Moreira Brito, Júlio César | Cestari, Marta Margarete | Prodocimo, Maritana Mela | Gomes, Marcelo Pedrosa | Silva de Assis, Helena Cristina
Ciprofloxacin (Cipro) is commonly detected in water worldwide, however, the ecotoxicological effects to aquatic biota is still not fully understood. In this study, using multiple biomarkers, it was investigated sublethal effects of short-term exposure to Cipro concentrations (1, 10 and 100 μg.L⁻¹) in the Neotropical catfish Rhamdia quelen compared to non-exposure treatment (Control). After 96 h of exposure, the fishes were anesthetized for blood collection to hematological and genotoxicity biomarkers analysis. After euthanasia, the brain and muscle were sampled for biochemical biomarkers analyses. Gills, liver and posterior kidney for genotoxicity, biochemical and histopathological biomarkers analysis and anterior intestine for histopathological biomarkers analysis. Genotoxicity was observed in all tissues, regardless of the Cipro concentrations. Hematological alterations, such as reduction of the number of erythrocytes and leucocytes, as well as in hematocrit concentration and histopathological damages, such as reduction of microridges in gill epithelium and necrosis in liver and posterior kidney, occurred mainly at 100 μg.L⁻¹. In addition, at 100 μg.L⁻¹, Cipro increased antioxidant system activity (Catalase in liver and posterior kidney). These results demonstrated that under short-term exposure, Cipro causes toxic effects in R. quelen that demands attention and surveillance of environmental aquatic concentrations of this antibiotic.
Показать больше [+] Меньше [-]Tracking gene expression, metabolic profiles, and biochemical analysis in the halotolerant basidiomycetous yeast Rhodotorula mucilaginosa EXF-1630 during benzo[a]pyrene and phenanthrene biodegradation under hypersaline conditions
2021
Martínez-Ávila, Liliana | Peidro-Guzmán, Heidy | Pérez-Llano, Yordanis | Moreno Perlín, Tonatiuh | Sánchez-Reyes, Ayixon | Aranda, Elisabet | Ángeles de Paz, Gabriela | Fernández-Silva, Arline | Folch-Mallol, Jorge Luis | Cabana, Hubert | Gunde-Cimerman, Nina | Batista-García, Ramón Alberto
Polyaromatic phenanthrene (Phe) and benzo[a]pyrene (BaP) are highly toxic, mutagenic, and carcinogenic contaminants widely dispersed in nature, including saline environments. Polyextremotolerant Rhodotorula mucilaginosa EXF-1630, isolated from Arctic sea ice, was grown on a huge concentration range -10 to 500 ppm- of Phe and BaP as sole carbon sources at hypersaline conditions (1 M NaCl). Selected polycyclic aromatic hydrocarbons (PAHs) supported growth as well as glucose, even at high PAH concentrations. Initially, up to 40% of Phe and BaP were adsorbed, followed by biodegradation, resulting in 80% removal in 10 days. While extracellular laccase, peroxidase, and un-specific peroxygenase activities were not detected, NADPH-cytochrome c reductase activity peaked at 4 days. The successful removal of PAHs and the absence of toxic metabolites were confirmed by toxicological tests on moss Physcomitrium patens, bacterium Aliivibrio fischeri, human erythrocytes, and pulmonary epithelial cells (A549). Metabolic profiles were determined at the midpoint of the biodegradation exponential phase, with added Phe and BaP (100 ppm) and 1 M NaCl. Different hydroxylated products were found in the culture medium, while the conjugative metabolite 1-phenanthryl-β-D-glucopyranose was detected in the medium and in the cells. Transcriptome analysis resulted in 870 upregulated and 2,288 downregulated transcripts on PAHs, in comparison to glucose. Genomic mining of 61 available yeast genomes showed a widespread distribution of 31 xenobiotic degradation pathways in different yeast lineages. Two distributions with similar metabolic capacities included black yeasts and mainly members of the Sporidiobolaceae family (including EXF-1630), respectively. This is the first work describing a metabolic profile and transcriptomic analysis of PAH degradation by yeast.
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