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Screening and validation of biomarkers for cadmium-induced liver injury based on targeted bile acid metabolomics
2022
Tian, Meng | Yan, Jun | Zhang, Honglong | Wei, Yuhui | Zhang, Mingtong | Rao, Zhi | Zhang, Mingkang | Wang, Haiping | Wang, Yanping | Li, Xun
Although cadmium (Cd) is a toxic heavy metal that reportedly causes liver injury, few studies have investigated biomarkers of Cd-induced liver injury. The purpose of this study is to investigate the role of bile acid (BA) in Cd-induced liver injury and determine reliable and sensitive biochemical parameters for the diagnosis of Cd-induced liver injury. In this study, 48 Sprague-Dawley rats were randomly divided into six groups and administered either normal saline or 2.5, 5, 10, 20, and 40 mg/kg/d cadmium chloride for 12 weeks. A total of 403 subjects living in either a control area (n = 135) or Cd polluted area (n = 268) of Dongdagou-Xinglong (DDGXL) cohort were included, a population with long-term low Cd exposure. The BA profiles in rats' liver, serum, caecal contents, faeces, and subjects' serum were detected using high-performance liquid chromatography-tandem mass spectrometry (HPLC–MS/MS). Changes in rats' and subjects' liver injury indices, rats' liver pathological degeneration, and rats' liver and subjects’ blood Cd levels were also measured. Cadmium exposure caused cholestasis and an increase in toxic BAs, leading to liver injury in rats. Among them, glycoursodeoxycholic acid (GUDCA), glycolithocholic acid (GLCA), taurolithocholic acid (TLCA), and taurodeoxycholate acid (TDCA) are expected to be potential biomarkers for the early detect of Cd-induced liver injury. Serum BAs can be used to assess Cd-induced liver injury as a simple, feasible, and suitable method in rats. Serum GUDCA, GLCA, TDCA, and TLCA were verified to be of value to evaluate Cd-induced liver injury and Cd exposure in humans. These findings provided evidence for screening and validation of additional biomarkers for Cd-induced liver injury based on targeted BA metabolomics.
显示更多 [+] 显示较少 [-]Organ-specific accumulation of cadmium and zinc in Gammarus fossarum exposed to environmentally relevant metal concentrations
2022
Gestin, Ophélia | Lopes, Christelle | Delorme, Nicolas | Garnero, Laura | Geffard, Olivier | Lacoue-Labarthe, Thomas
One of the best approaches for improving the assessment of metal toxicity in aquatic organisms is to study their organotropism (i.e., the distribution of metals among organs) through a dynamical approach (i.e., via kinetic experiments of metal bioaccumulation), to identify the tissues/organs that play a key role in metal regulation (e.g., storage or excretion). This study aims at comparing the organ-specific metal accumulation of a non-essential (Cd) and an essential metal (Zn), at their environmentally relevant exposure concentrations, in the gammarid Gammarus fossarum. Gammarids were exposed for 7 days to ¹⁰⁹Cd- or ⁶⁵Zn-radiolabeled water at a concentration of 52.1 and 416 ng.L⁻¹ (stable equivalent), respectively, and then placed in clean water for 21 days. At different time intervals, the target organs (i.e., caeca, cephalons, intestines, gills, and remaining tissues) were collected and ¹⁰⁹Cd or ⁶⁵Zn contents were quantified by gamma-spectrometry. A one-compartment toxicokinetic (TK) model was fitted by Bayesian inference to each organ/metal dataset in order to establish TK parameters. Our results indicate: i) a contrasting distribution pattern of concentrations at the end of the accumulation phase (7ᵗʰ day): gills > caeca ≈ intestines > cephalons > remaining tissues for Cd and intestines > caeca > gills > cephalons > remaining tissues for Zn; ii) a slower elimination of Cd than of Zn by all organs, especially in the gills in which the Cd concentration remained constant during the 21-day depuration phase, whereas Zn concentrations decreased sharply in all organs after 24 h in the depuration phase; iii) a major role of intestines in the uptake of waterborne Cd and Zn at environmentally relevant concentrations.
显示更多 [+] 显示较少 [-]Dioxin-like PCB 126 increases intestinal inflammation and disrupts gut microbiota and metabolic homeostasis
2018
Petriello, Michael C. | Hoffman, Jessie B. | Vsevolozhskaya, Olga | Morris, Andrew J. | Hennig, Bernhard
The gut microbiome is sensitive to diet and environmental exposures and is involved in the regulation of host metabolism. Additionally, gut inflammation is an independent risk factor for the development of metabolic diseases, specifically atherosclerosis and diabetes. Exposures to dioxin-like pollutants occur primarily via ingestion of contaminated foods and are linked to increased risk of developing cardiometabolic diseases. We aimed to elucidate the detrimental impacts of dioxin-like pollutant exposure on gut microbiota and host gut health and metabolism in a mouse model of cardiometabolic disease. We utilized 16S rRNA sequencing, metabolomics, and regression modeling to examine the impact of PCB 126 on the microbiome and host metabolism and gut health. 16S rRNA sequencing showed that gut microbiota populations shifted at the phylum and genus levels in ways that mimic observations seen in chronic inflammatory diseases. PCB 126 reduced cecum alpha diversity (0.60 fold change; p = 0.001) and significantly increased the Firmicutes to Bacteroidetes ratio (1.63 fold change; p = 0.044). Toxicant exposed mice exhibited quantifiable concentrations of PCB 126 in the colon, upregulation of Cyp1a1 gene expression, and increased markers of intestinal inflammation. Also, a significant correlation between circulating Glucagon-like peptide-1 (GLP-1) and Bifidobacterium was evident and dependent on toxicant exposure. PCB 126 exposure disrupted the gut microbiota and host metabolism and increased intestinal and systemic inflammation. These data imply that the deleterious effects of dioxin-like pollutants may be initiated in the gut, and the modulation of gut microbiota may be a sensitive marker of pollutant exposures.
显示更多 [+] 显示较少 [-]Effects of phenanthrene on different levels of biological organization in larvae of the sediment-dwelling invertebrate Chironomus sancticaroli (Diptera: Chironomidae)
2018
Richardi, V.S. | Vicentini, M. | Morais, G.S. | Rebechi, D. | da Silva, T.A. | Fávaro, L.F. | Navarro-Silva, M.A.
The hydrocarbon phenanthrene is an organic compound commonly found in the environment. In aquatic ecosystems, it is highly toxic to organisms, although little is known about its effects on sediment-dwelling organisms. The purpose of this study was to evaluate phenanthrene effects on biochemical, histological, and ontogenetic levels in larvae of the sediment-dwelling invertebrate Chironomus sancticaroli at acute and chronic exposure. Lethal concentrations were estimated and toxicity (acute-96 h and chronic- 8 d) tests were performed at phenanthrene concentrations from 0.12 to 1.2 mg L⁻¹. At acute and chronic exposure, we evaluated acetylcholinesterase (AChE), alpha esterase (EST-α), and beta esterase (EST-β) activities as well as histological alterations. In the assays with chronic exposure, effects on larval development were estimated using antennae length (instar estimative) and body length (growth estimative). The EST-α showed a significantly increased activity after 48 h at acute exposure to high concentrations of phenanthrene, while EST-β activity was increased after 48 and 72 h at acute exposure at higher concentrations and at 0.12 mg L⁻¹ at chronic exposure. At acute exposure, the midgut showed alterations such as brush border disruption, gastric caeca regression, and lumen area reduction; the fat body showed nuclear alteration in the trophocytes, while the Malpighian tubules showed brush border reduction and the salivary glands were subject to cytoplasm vacuolation. At chronic exposure, the same alterations were observed, in addition to vacuolar coalescence in the trophocytes of the fat body. Regarding larval development, a reduction of body length was observed with increasing phenanthrene concentrations. Similarly, molting was delayed; in the control group, all larvae were in the fourth instar, while at higher phenanthrene concentrations, larvae were predominantly in the third instar. Phenanthrene had toxic effects on this chironomid, indicating risks for natural populations.
显示更多 [+] 显示较少 [-]Ecotoxicoproteomic assessment of the functional alterations caused by chronic metallic exposures in gammarids
2017
Gismondi, E. | Thomé, J.-P. | Urien, N. | Uher, E. | Baiwir, D. | Mazzucchelli, G. | De Pauw, E. | Fechner, L.C. | Lebrun, J.D.
Very few ecotoxicological studies have been performed on long-term exposure under controlled conditions, hence limiting the assessment of the impact of chronic and diffuse chemical pressures on the health of aquatic organisms. In this study, an ecotoxicoproteomic approach was used to assess the integrated response and possible acclimation mechanisms in Gammarus fossarum following chronic exposures to Cd, Cu or Pb, at environmentally realistic concentrations (i.e. 0.25, 1.5 and 5 μg/L respectively). After 10-week exposure, changes in protein expression were investigated in caeca of control and exposed males. Gel-free proteomic analyses allowed for the identification of 35 proteins involved in various biological functions, for which 23 were significantly deregulated by metal exposures. The protein deregulation profiles were specific to each metal, providing evidence for metal-specific action sites and responses of gammarids. Among the tested metals, Cu was the most toxic in terms of mortality, probably linked with persistent oxidative stress. Moulting and osmoregulation were the major biological functions affected by Cu in the long-term. In Pb-exposed gammarids, significant deregulations of proteins involved in immune response and cytoskeleton were observed. Reproduction appears to be strongly affected in gammarids chronically exposed to Cd or Pb. Besides, modified expressions of several proteins involved in energy transfer and metabolism highlighted important energetic reshuffling to cope with chronic metal exposures. These results support the fact that metallic pressures induce a functional and energetic cost for individuals of G. fossarum with potential repercussions on population dynamics. Furthermore, this ecotoxicoproteomic study offers promising lines of enquiry in the development of new biomarkers that could make evidence of long-term impacts of metals on the health of organisms.
显示更多 [+] 显示较少 [-]Bisphenol A alters gut microbiome: Comparative metagenomics analysis
2016
Lai, Keng-Po | Chung, Yan-Tung | Li, Rong | Wan, Hin-Ting | Wong, Chris Kong-Chu
Mounting evidence has shown that an alteration of the gut microbiota is associated with diet, and plays an important role in animal health and metabolic diseases. However, little is known about the influence of environmental contaminants on the gut microbial community. Bisphenol A (BPA), which is widely used for manufacturing plastic products, has recently been classified as an environmental obesogen. Although many studies have demonstrated the metabolic-disrupting effects of BPA on liver and pancreatic functions, the possible effects of this synthetic compound on the metabolic diversity of the intestinal microbiota is unknown. Using 16S rRNA gene sequencing analysis on caecum samples of CD-1 mice, the present study aimed to test the hypothesis that dietary BPA intake may influence the gut microbiota composition and functions, an important attributing factor to development of the metabolic syndrome. A high-fat diet (HFD) and high-sucrose diet (HSD) were included as the positive controls for comparing the changes in the intestinal microbial profiles. Our results demonstrated a significant reduction of species diversity in the gut microbiota of BPA-fed mice. Alpha and beta diversity analyses showed that dietary BPA intake led to a similar gut microbial community structure as that induced by HFD and HSD in mice. In addition, comparative analysis of the microbial communities revealed that both BPA and a HFD favored the growth of Proteobacteria, a microbial marker of dysbiosis. Consistently, growth induction of the family Helicobacteraceae and reduction of the Firmicutes and Clostridia populations were observed in the mice fed BPA or a HFD. Collectively, our study highlighted that the effects of dietary BPA intake on the shift of microbial community structure were similar to those of a HFD and HSD, and revealed microbial markers for the development of diseases associated with an unstable microbiota.
显示更多 [+] 显示较少 [-]Bacillus coagulans R11 consumption influenced the abundances of cecum antibiotic resistance genes in lead-exposed laying hens
2021
Xing, Si-Cheng | Chen, Jing-Yuan | Cai, Ying-Feng | Huang, Chun-Bo | Liao, Xin-Di | Mi, Jian-Dui
Bacillus coagulans is regarded as a clean, safe and helpful probiotic additive in the production of livestock and poultry breeds. Some studies have also shown that Bacillus coagulans can adsorb heavy metals in water, even in the gut of animals. However, whether Bacillus coagulans feeding influences antibiotic resistance gene (ARG) abundance in the gut of lead-exposed laying hens is unknown. To better apply such probiotics in the breeding industry, the present study employed Bacillus coagulans R11 and laying hens in model experiments to test ARG changes in the cecum of laying hens under lead exposure and B. coagulans R11 feeding. The results showed that there was the trend for ARG abundance decreasing in feeding B. coagulans R11 without lead exposure to laying hens in the cecum; however, feeding B. coagulans R11 to laying hens exposed to lead obviously increased the abundances of aminoglycoside and chloramphenicol ARGs. Further experiment found that hydroquinone, dodecanedioic acid, gibberellin A14, alpha-solanine, jasmonic acid and chitin were involved in the abundances of ARGs in the cecum, in addition the abundances of these compounds were also significantly enhanced by lead exposure or combination effects of lead and B. coagulans R11. As a result, the ARG hazards increased with feeding B. coagulans R11 to laying hens exposed to lead, and the key compounds which influenced by the combination effects of lead and B. coagulans R11 might influence the ARGs abundance.
显示更多 [+] 显示较少 [-]Exposure to methylmercury and inorganic mercury in the food does not lead to trophic magnification in the sea star Asterias rubens
2021
Bjerregaard, Poul | Møller, Lise Marianne
Methylmercury accumulated at the top of aquatic food chains constitutes a toxicological risk to humans and other top predators. Biomagnification of methylmercury takes place among vertebrates at the higher trophic levels, but this process is less elucidated in benthic invertebrates at the lower trophic levels. Therefore, we investigated the accumulation from food and elimination of methylmercury and inorganic mercury in the benthic sea star Asterias rubens (L.) – a representative of trophic level ~3 - in laboratory experiments. Sea stars fed over 49 days with contaminated mussels (Mytilus edulis) accumulate methylmercury and inorganic mercury to the highest concentrations in the digestive glands, the pyloric caeca, less in stomach, gonad, tube feet, aboral body wall and not to detectable levels in the coelomic fluid. Concerning whole body contents, steady states were reached for both methylmercury and inorganic mercury during the 7-week feeding period and the sea stars reached approximately ½ and ¼ of the concentrations in the mussel food for the two mercury forms, respectively. Half-lives for the elimination of the two mercury forms varied between 45 and 173 days in a 140-d elimination period following the feeding period; inorganic mercury was eliminated faster than methylmercury. Examination of total mercury concentrations in field-collected sea stars confirmed this lack of trophic magnification in relation to the major food items, soft parts of molluscs. We suggest that mercury is not trophically magnified in sea stars 1) because they eliminate methylmercury faster than larger fish and decapod crustaceans and 2) maybe more importantly, because inorganic mercury with its faster elimination constitutes a larger fraction of the total mercury in the food at the lower trophic levels - as opposed to methylmercury which dominates at the higher trophic levels.
显示更多 [+] 显示较少 [-]Use of the sea hare (Aplysia fasciata) in marine pollution biomonitoring of harbors and bays
2018
Dirrigl, Frank J. | Badaoui, Zachariah | Támez, Carlos | Vitek, Christopher J. | Parsons, Jason G.
Our study evaluated heavy metal concentrations in soft tissues of sea hare, Aplysia fasciata, from the Lower Laguna Madre, Texas. Heavy metals in tissues followed Se>As>Pb>Cd. Concentrations ranged As (BDL-28.08), Cd (BDL-5.50), Pb (BDL-12.85) and Se (4.25–93.43ppm). Median As, Cd, Pb, and Se tissue levels exceeded exposure levels. Significant relationships occurred in metal-metal (AsCd, AsPb, CdPb, CdSe, and PbSe), metal-tissue (significant Se uptake by inhalant and exhalant siphons and As in the hepatopancreas), and metal-metal within tissue (AsPb in the hepatopancreas and CdPb in the digestive cecum) analyses (p<0.05). Bioaccumulation factors (BAF) suggested the inhalant siphon, hepatopancreas, and digestive cecum function as macroconcentrators of Cd, hepatopancreas and digestive cecum as macroconcentrators of Pb, and all tissues were deconcentrators for As and Se. As a bioaccumulator of heavy metals, Aplysia was evaluated as a bioindicator of marine pollution in harbors and bays.
显示更多 [+] 显示较少 [-]Microplastics presence in cultured and wild-caught cuttlefish, Sepia officinalis
2020
Oliveira, Ana R. | Sardinha-Silva, Andreia | Andrews, Paul L.R. | Green, Dannielle | Cooke, Gavan M. | Hall, Sarah | Blackburn, Kirsty | Sykes, António V.
Amongst cephalopods microplastics have been reported only in jumbo squid gut. We investigated microplastics in the digestive system of wild cuttlefish (Sepia officinalis) as they are predators and prey and compared the stomach, caecum/intestine and digestive gland (DG) of wild and cultured animals, exposed to seawater from a comparable source. Fibers were the most common type (≈90% of total count) but were ≈2× higher in relation to body weight in wild vs. cultured animals. Fibers were transported to the DG where the count was ≈2× higher /g in wild (median 1.85 fibers/g) vs. cultured. In wild-caught animals the DG was the predominant location but in cultured animals the fibers were more evenly distributed in the digestive tract. The potential impact of microplastics on health of cuttlefish is discussed. Cuttlefish represent a previously unrecognized source of microplastic trophic transfer to fish and finding fibers in cultured animals has implications for aquaculture.
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