Refine search
Results 1-7 of 7
Hexavalent chromium induces mitochondrial dynamics disorder in rat liver by inhibiting AMPK/PGC-1α signaling pathway
2020
Yang, Qingyue | Han, Bing | Xue, Jiangdong | Lv, Yueying | Li, Siyu | Liu, Yan | Wu, Pengfei | Wang, Xiaoqiao | Zhang, Zhigang
Occupational exposure to hexavalent chromium (Cr(VI)) can cause cytotoxicity and carcinogenicity. In this study, we established a liver injury model in rats via intraperitoneal injection of potassium dichromate (0, 2, 4, and 6 mg/kg body weight) for 35 d to investigate the mechanism of Cr(VI)-induced liver injury. We found that Cr(VI) induced hepatic histopathological lesions, oxidative stress, and apoptosis and reduced the expression of mitochondrial-related regulatory factors such as adenosine 5′-monophosphate-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) in a dose-dependent manner. Furthermore, Cr(VI) promoted mitochondrial division and inhibited fusion, leading to increased expression of caspase-3 and production of mitochondrial reactive oxygen species. Our study demonstrates that long-term exposure to Cr(VI) induces mitochondrial dynamics disorder by inhibiting AMPK/PGC-1α signaling pathway in rat liver.
Show more [+] Less [-]Metabolic profiling study on potential toxicity in male mice treated with Dechlorane 602 using UHPLC-ESI-IT-TOF-MS
2019
Tao, Wuqun | Tian, Jijing | Xu, Tuan | Xu, Li | Xie, Heidi Qunhui | Zhou, Zhiguang | Guo, Zhiling | Fu, Hualing | Yin, Xuejiao | Chen, Yangsheng | Xu, Haiming | Zhang, Songyan | Zhang, Wanglong | Ma, Chao | Ji, Feng | Yang, Jun | Zhao, Bin
Dechlorane 602 (Dec 602), a chlorinated flame retardant, has been widely detected in different environmental matrices and biota. However, toxicity data for Dec 602 seldom have been reported. A metabolomics study based on ultra-high performance liquid chromatography coupled with ion trap time-of-flight mass spectrometry was employed to study the urine and sera metabolic profiles of mice administered with Dec 602 (0, 0.001, 0.1, and 10 mg/kg body weight per day) for 7 days. A significant difference in metabolic profiling was observed between the Dec 602 treated group and the control group by multivariate analysis, which directly reflected the metabolic perturbations caused by Dec 602. The metabolomics analyses of urine from Dec 602-exposed animals exhibited an increase in the levels of thymidine and tryptophan as well as a decrease in the levels of tyrosine, 12,13-dihydroxy-9Z-octadecenoic acid, 2-hydroxyhexadecanoic acid and cuminaldehyde. The metabolomics analyses of sera showed a decrease in the levels of kynurenic acid, daidzein, adenosine, xanthurenic acid and hypoxanthine from Dec 602-exposed animals. These findings indicated Dec 602 induced disturbance in phenylalanine, tyrosine and tryptophan biosynthesis, tryptophan metabolism, tyrosine metabolism, pyrimidine metabolism, purine metabolism, ubiquinone and other terpenoid-quinone biosynthesis; phenylalanine metabolism and aminoacyl-tRNA biosynthesis. Significant alterations of immune and neurotransmitter-related metabolites (tyrosine, tryptophan, kynurenic acid, and xanthurenic acid) suggest that the toxic effects of Dec 602 may contribute to its interactions with the immune and neuronal systems. This study demonstrated that the UHPLC-ESI-IT-TOF-MS-based metabolomic approach can obtain more specific insights into the potential toxic effects of Dec 602 at molecular level.
Show more [+] Less [-]Dissolved organic phosphorus enhances arsenate bioaccumulation and biotransformation in Microcystis aeruginosa
2019
Wang, Zhenhong | Gui, Herong | Luo, Zhuanxi | Zhen, Zhuo | Yan, Changzhou | Xing, Baoshan
Only limited information is available on the effects of dissolved organic phosphorus (DOP) on arsenate (As(V)) bioaccumulation and biotransformation in organisms. In this study, we examined the influence of three different DOP forms (β-sodium glycerophosphate (βP), adenosine 5′-triphosphate (ATP), and D-Glucose-6-phosphate disodium (GP) salts) and inorganic phosphate (IP) on As(V) toxicity, accumulation, and biotransformation in Microcystis aeruginosa. Results showed that M. aeruginosa utilized the three DOP forms to sustain its growth. At a subcellular level, the higher phosphorus (P) distribution in metal-sensitive fractions (MSF) observed in the IP treatments could explain the comparatively lower toxic stress of algae compared to the DOP treatments. Meanwhile, the higher MSF distribution of arsenic (As) in M. aeruginosa in the presence of DOP could explain the higher toxicity with lower 96-h half maximal effective concentration (EC50) values. Although we observed As(V) and P discrimination in M. aeruginosa under IP treatments with high intracellular P/As, we did not find this discrimination under the DOP treatments. As accumulation in algal cells was therefore greatly enhanced by DOP, especially βP, given its lower transformation rate to phosphate compared to ATP and GP in media. Additionally, As(V) reduction and, subsequently, As(III) methylation were greatly facilitated in M. aeruginosa by the presence of DOP, particularly GP, which was confirmed by the higher relative expression of its two functional genes (arsC and arsM). Our findings indicate that As(V) accumulation and its subsequent biotransformation were enhanced by organic P forms, which provides new insight into how DOP modulates As metabolism in algae.
Show more [+] Less [-]Altered Gene expression of ABC transporters, nuclear receptors and oxidative stress signaling in zebrafish embryos exposed to CdTe quantum dots
2019
Tian, Jingjing | Hu, Jia | Liu, Guangxing | Yin, Huancai | Chen, Mingli | Miao, Peng | Bai, Pengli | Yin, Jian
Adenosine triphosphate-binding cassette (ABC) transporters, including P-glycoprotein (Pgp) and multi-resistance associated proteins (Mrps), have been considered important participants in the self-protection of zebrafish embryos against environmental pollutants, but their possible involvement in the efflux and detoxification of quantum dots (QDs), as well as their regulation mechanism are currently unclear. In this work, gene expression alterations of ABC transporters, nuclear receptors, and oxidative stress signaling in zebrafish embryos after the treatment of mercaptopropionic acid (MPA)CdTe QDs and MPA-CdSCdTe QDs were investigated. It was observed that both QDs caused concentration-dependent delayed hatching effects and the subsequent induction of transporters like mrp1&2 in zebrafish embryos, indicating the protective role of corresponding proteins against CdTe QDs. Accompanying these alterations, expressions of nuclear receptors including the pregnane X receptor (pxr), aryl hydrocarbon receptor (ahr) 1b, and peroxisome proliferator-activated receptor (ppar)-β were induced by QDs in a concentration- and time-dependent manner. Moreover, elevated oxidative stress, reflected by the reduction of glutathione (GSH) level and superoxide dismutase (SOD) activities, as well as the dramatic induction of nuclear factor E2 related factor (nrf) 2, was also found. More importantly, alterations of pxr and nrf2 were more pronounced than that of mrps, and these receptors exhibited an excellent correlation with delayed hatching rate in the same embryos (R² > 0.8). Results from this analysis demonstrated that the induction of mrp1 and mrp2 could be important components for the detoxification of QDs in zebrafish embryos. These transporters could be modulated by nuclear receptors and oxidative stress signaling. In addition, up-regulation of pxr and nrf2 could be developed as toxic biomarkers of CdTe QDs.
Show more [+] Less [-]Phosphorus-based metabolic pathway tracers in surface waters
2021
Packa, Vlastimil | Howell, Todd | Bostan, Vadim | Furdui, Vasile I.
Trophic status in surface waters has been mostly monitored by measuring soluble reactive phosphorus (SRP) and total phosphorus (TP). Additional to these common parameters, a two-dimensional ion chromatography mass spectrometry (2D-IC-MS) method was used to simultaneously measure soluble phosphate (Pi), pyrophosphate (PPi), and eleven phosphate-containing metabolites (P-metabolites) in Lake Ontario and its tributaries. From the additional P species, PPi, adenosine 5′-monophosphate (AMP), glucose 6-phosphate (G-P), D-fructose 6-phosphate (F-P), D-fructose 1,6-biphosphate (F-2P), D-ribulose 5-phosphate (R-P), D-ribulose 1,5-bisphosphate (R-2P), and D-(-)-3-phosphoglyceric acid (PGA) were detected and quantified in the lake and river samples. The additional multivariate statistical analysis identified similarities between samples collected at different locations. The presence of R-P, R-2P, and F-2P in Lake Ontario tributaries seems to be mainly related to the Calvin cycle, while the lack of all these three P-metabolites and higher PGA levels than G-P in Toronto Harbour samples seems to be the result of depleted Calvin cycle, pentose phosphate, and glycolysis metabolic pathways.
Show more [+] Less [-]Antagonistic effects of nano-selenium on broilers hepatic injury induced by Cr(VI) poisoning in AMPK pathway
2020
Zhang, Tian-guang | Zhao, Ya-li | Li, Lei | Zhou, Dong-hai
Cr (chromium, with common valence states of III and VI) is one of the common broiler feed additives. Liver injury and metabolic disorders could be caused by Cr₍VI₎ (hexavalent chromium) poisoning in broilers. Oxidative damage and metabolic disorders of organisms caused by heavy metals could be antagonized by nano-Se (nano-selenium). Nano-Se was chosen to study the antagonism of Cr₍VI₎ poisoning in broilers. AMPK (Adenosine 5,-monophosphate-activated protein kinase) is known as a “cell energy regulator” and plays a key regulatory role in carbohydrate and lipid metabolism. AMPK pathway and ACACA/CPT1A two genes were selected to study the prevention and treatment of nano-Se on Cr₍VI₎ poisoning in broilers and its molecular mechanism. For this purpose, 180 1-day-old AA (Arbor Acres) broilers were selected and randomly divided into 6 groups (n = 30) for further testing. After feeding as planned for 35 days, the livers of such broilers were taken for further examination including histopathological examination, differential gene expression analysis, and further validation on both mRNA and protein levels using related techniques like RT-qPCR, western blot, and immunohistochemistry (IHC). The histopathological examination suggested that the liver cells of the Cr₍VI₎ poisoning group were more severely injured than the nano-Se addition group. RT-qPCR results showed that the relative expression of ACACA gene in the Cr₍VI₎ poisoning group was significantly increased (P < 0.05), while the CPT1A gene’s expression was significantly decreased (P < 0.01). Those results were reversed in the nano-Se addition group. Western blot results were consistent with RT-qPCR and both suggested antagonism of nano-Se on Cr₍VI₎. Through morphological and histopathological observation, as well as the measurement of the mRNA and protein expression levels of ACACA and CPT1A genes in AMPK pathway, it was confirmed that nano-Se has certain preventive and protective effects on Cr₍VI₎ poisoning in broiler chickens. Furthermore, the adverse effects of Cr₍VI₎ on carbohydrate and lipid metabolism in broilers can be antagonized by nano-Se through AMPK pathway. A new method and experimental basis were provided to the future study of Cr₍VI₎ poisoning in broilers.
Show more [+] Less [-]Detection of DNA damage in fish Oreochromis mossambicus induced by co-exposure to phenanthrene and nitrite by ESI-MS/MS
2010
Wahidulla, Solimabi | Rajamanickam, Yeziel Rani
Background, aim, and scope Mutagenic nitrated polycyclic aromatic hydrocarbons (nitro-PAHs) have been known to arise in the environment through direct emissions from combustion sources and nitration of PAHs, primarily in the atmosphere. In the marine environment, PAHs are one of the classic anthropogenic organic pollutants, while nitrite (NO ₂ ⁻ ) is produced naturally via various biological processes like imbalance in nitrification/denitrification or eutrophication and subsequent oxygen depletion from an oversupply of nutrients. In this paper, we report the formation of PAH-DNA adducts in fish contaminated with PAHs and exposed to NO ₂ ⁻ in the ambient water. Electrospray ionization tandem mass spectrometric (ESI-MS/MS) analysis of the bile of the euryhaline fish Oreochromis mossambicus exposed simultaneously to field relevant sublethal concentrations of phenanthrene and NO ₂ ⁻ and collision-induced dissociation of selected ions revealed the presence of DNA-PAH adducts. The present study indicates that, although several high sensitivity techniques have been developed for the analysis of PAH derived DNA adducts, MS/MS has emerged as a powerful tool in the detection and structure elucidation of DNA adducts. Materials and methods Juvenile O. mossambicus from a local estuarine fish farm were used with increasing frequency for carcinogenicity testing and comparative cancer research. The fish were exposed to the alkylating agent phenanthrene in the presence of NO ₂ ⁻ . Composite untreated bile samples after dilution with methanol: water (1:1; v/v) were analyzed by ESI-MS. Results Several adducts could be evidenced in the bile by MS/MS. Deoxyadenosine/deoxyguanosine having a mass in the range of 450-650 amu is detected. In addition, a segment of modified dinucleotide with a mass that corresponds to a dimer consisting of a modified guanosine and a normal guanosine has also been identified in the bile. Discussion The formation of certain types of DNA adducts is a crucial step in the induction of cancer and a primary stage in mutagenesis. Phenanthrene injected by i.p. route led to the transformation of phenanthrene to N-formyl amino phenanthrene-N ⁶-deoxyadenosine adduct, whereas the fish co-exposed to phenanthrene and ambient nitrite metabolizes PAH to mono-, di- as well as trinitro derivatives, which then react with DNA leading to the formation of mainly modified guanosine and adenosine adducts. In the present investigation, dinitrophenanthrene diol epoxide (DNPDE) adduct with guanosine (m/z 587) seems to be the dominant adduct in the mixture, and its presence is shown first as a comparatively less stable adduct, which decomposes to give a more stable N² adduct (m/z 567). Conclusions MS/MS has proved to be useful in the rapid determination and discrimination of structurally different phenanthrene/derivatives DNA adducts in a complex mixture of fish bile co-exposed to phenanthrene and nitrite. However, the nature of metabolites formed is likely determined by the route of PAH administration, and there is a need to further define the early biochemical events of carcinogenesis in these species. Recommendations and perspectives DNA adduct analysis in fish bile offers a promising approach to study the risk of potentiation of anthropogenic chemicals into genotoxic compounds in the presence of nitrite in the marine environment. We believe this is the first report on the formation of DNA-phenanthrene adducts on co-exposure of the fish to PAH and nitrite.
Show more [+] Less [-]