Integrated 1H NMR-based metabolomics analysis of earthworm responses to sub-lethal Pb exposure
Ting Chen A , Yan Liu A , Ming-Hui Li A , Hua-Dong Xu A , Ji-Yang Sheng A , Li Zhang A B and Jun-Song Wang A B
+ Author Affiliations
- Author Affiliations
A Centre for Molecular Metabolism, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing 210094, China.
B Corresponding authors. Email: wang.junsong@gmail.com; njust_zhangli@163.com
Environmental Chemistry 13(5) 792-803 https://doi.org/10.1071/EN15192
Submitted: 16 September 2015 Accepted: 5 February 2016 Published: 23 March 2016
Environmental context. Heavy metals are non-degradable and are therefore a severe and persistent environmental menace. The toxic effects of Pb were investigated using NMR to determine the metabolic changes in earthworms exposed to Pb. The approach using 1H NMR to analyse earthworm metabolomics demonstrated great potential as a reliable, rapid and convenient tool to assess the toxicity of heavy metals and could be used to identify warning signs of heavy metal contamination of soil.
Abstract. A 1H nuclear magnetic resonance (NMR)-based approach to metabolomics combined with atomic absorption spectroscopy, histopathological examination and biochemical assessment was used to determine the toxic effects of lead (Pb) on earthworms (Eisenia fetida). Earthworms were exposed to Pb in a lead nitrate solution at converted concentrations of 1.25, 5.0 and 20 µg cm–2 in contact tests for 48 h. Based on histopathological inspection, the epidermis, muscles, chloragogenous tissues and intestinal epithelium were severely impaired. Based on biochemical assessment, a disruption of the antioxidative system and neurotoxic effects in earthworms occurred following exposure to Pb. Orthogonal signal correction–partial least-squares-discriminant analysis of NMR profiles indicated that Pb exposure in earthworms caused widespread metabolic changes, which were associated with oxidative stress, neurotransmitter imbalance, disruption of osmotic equilibrium and interference in energy metabolism and nucleic acid metabolism. The integrated metabolomics approach provided new insights into Pb-induced toxicity in earthworms. Metabolomics is a powerful and highly effective approach and has great promise to determine the ecotoxicological effects and the underlying mechanisms of toxicity of heavy metals.
Additional keywords: contact test, Eisenia fetida, lead, toxicity.
References
[1] M. L. Brusseau, Transport and fate of toxicants in soil, in Soil Ecotoxicology 1996, p. 33 (Lewis: Boca Raton, FL, USA).[2] S. Khan, Q. Cao, Y. Zheng, Y. Huang, Y. Zhu, Health risks of heavy metals in contaminated soils and food crops irrigated with wastewater in Beijing, China. Environ. Pollut. 2008, 152, 686.
| Health risks of heavy metals in contaminated soils and food crops irrigated with wastewater in Beijing, China.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXktFentrY%3D&md5=509f617d617ca4f8ccdff5c4b1a10f57CAS | 17720286PubMed |
[3] J. Cortet, A. G.-D. Vauflery, N. Poinsot-Balaguer, L. Gomot, C. Texier, D. Cluzeau, The use of invertebrate soil fauna in monitoring pollutant effects. Eur. J. Soil Biol. 1999, 35, 115.
| The use of invertebrate soil fauna in monitoring pollutant effects.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXjt1Gqur8%3D&md5=f59f59cd7383d273c098cb6fda439bcbCAS |
[4] A. A. Rida, M. Bouche, A method to assess chemical biorisks in terrestrial ecosystems, in Ecotoxicology of Soil Organisms 1994, pp. 373–394 (CRC Press: Boca Raton, FL, USA).
[5] S. Verma, R. Dubey, Lead toxicity induces lipid peroxidation and alters the activities of antioxidant enzymes in growing rice plants. Plant Sci. 2003, 164, 645.
| Lead toxicity induces lipid peroxidation and alters the activities of antioxidant enzymes in growing rice plants.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXisV2nu70%3D&md5=09a6b93f329c04547006c69d0a48e691CAS |
[6] B. J. Majer, D. Tscherko, A. Paschke, R. Wennrich, M. Kundi, E. Kandeler, S. Knasmüller, Effects of heavy metal contamination of soils on micronucleus induction in Tradescantia and on microbial enzyme activities: a comparative investigation. Mutat. Res. Genet. Toxicol. Environ. Mutagen. 2002, 515, 111.
| Effects of heavy metal contamination of soils on micronucleus induction in Tradescantia and on microbial enzyme activities: a comparative investigation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XitFWkurc%3D&md5=89ebaa749ed4b976a0569d6ad491ea81CAS |
[7] A. D. Woolf, R. Goldman, D. C. Bellinger, Update on the clinical management of childhood lead poisoning. Pediatr. Clin. North Am. 2007, 54, 271.
| Update on the clinical management of childhood lead poisoning.Crossref | GoogleScholarGoogle Scholar | 17448360PubMed |
[8] Y. Shao, W. Zhang, J. Shen, L. Zhou, H. Xia, W. Shu, H. Ferris, S. Fu, Nematodes as indicators of soil recovery in tailings of a lead/zinc mine. Soil Biol. Biochem. 2008, 40, 2040.
| Nematodes as indicators of soil recovery in tailings of a lead/zinc mine.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXnvVGhurg%3D&md5=704f1952a896dea535b442f9e6b6e14dCAS |
[9] P. Skubała, T. Zaleski, Heavy metal sensitivity and bioconcentration in oribatid mites (Acari, Oribatida): gradient study in meadow ecosystems. Sci. Total Environ. 2012, 414, 364.
| Heavy metal sensitivity and bioconcentration in oribatid mites (Acari, Oribatida): gradient study in meadow ecosystems.Crossref | GoogleScholarGoogle Scholar | 22134027PubMed |
[10] S. Suthar, S. Singh, S. Dhawan, Earthworms as bioindicator of metals (Zn, Fe, Mn, Cu, Pb and Cd) in soils: is metal bioaccumulation affected by their ecological category? Ecol. Eng. 2008, 32, 99.
| Earthworms as bioindicator of metals (Zn, Fe, Mn, Cu, Pb and Cd) in soils: is metal bioaccumulation affected by their ecological category?Crossref | GoogleScholarGoogle Scholar |
[11] C. Svendsen, D. Spurgeon, P. Hankard, J. Weeks, A review of lysosomal membrane stability measured by neutral red retention: is it a workable earthworm biomarker? Ecotoxicol. Environ. Saf. 2004, 57, 20.
| A review of lysosomal membrane stability measured by neutral red retention: is it a workable earthworm biomarker?Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXpsVSiu7g%3D&md5=d9a3f7f0db9ec69c22d5f67b873bf428CAS | 14659363PubMed |
[12] D. Spurgeon, S. Hopkin, D. Jones, Effects of cadmium, copper, lead and zinc on growth, reproduction and survival of the earthworm Eisenia fetida (Savigny): assessing the environmental impact of point-source metal contamination in terrestrial ecosystems. Environ. Pollut. 1994, 84, 123.
| Effects of cadmium, copper, lead and zinc on growth, reproduction and survival of the earthworm Eisenia fetida (Savigny): assessing the environmental impact of point-source metal contamination in terrestrial ecosystems.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2cXhvVCqtL8%3D&md5=8e3966ca8be48445acbc545dfd5dd5d5CAS | 15091707PubMed |
[13] D. J. Spurgeon, S. Hopkin, Extrapolation of the laboratory-based OECD earthworm toxicity test to metal-contaminated field sites. Ecotoxicology 1995, 4, 190.
| Extrapolation of the laboratory-based OECD earthworm toxicity test to metal-contaminated field sites.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2MXntV2rsrw%3D&md5=2d07daa467c8b2592c9435a61ebaade0CAS | 24197704PubMed |
[14] M. R. Viant, Recent developments in environmental metabolomics. Mol. Biosyst. 2008, 4, 980.
| Recent developments in environmental metabolomics.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXhtFeitrfK&md5=9bbec9a7ac6fbed87df3725660d678bbCAS | 19082136PubMed |
[15] M. J. Simpson, J. R. McKelvie, Environmental metabolomics: new insights into earthworm ecotoxicity and contaminant bioavailability in soil. Anal. Bioanal. Chem. 2009, 394, 137.
| Environmental metabolomics: new insights into earthworm ecotoxicity and contaminant bioavailability in soil.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhsFWisb0%3D&md5=dde7549422e999667f422f307cbf9b5fCAS | 19194697PubMed |
[16] C. Y. Lin, M. R. Viant, R. S. Tjeerdema, Metabolomics: methodologies and applications in the environmental sciences. J. Pestic. Sci. 2006, 31, 245.
| Metabolomics: methodologies and applications in the environmental sciences.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XpvFCksbc%3D&md5=cf30d79336f89fca71002ffbf82bedccCAS |
[17] B. P. Lankadurai, D. M. Wolfe, M. L. Whitfield Åslund, A. J. Simpson, M. J. Simpson, 1H NMR-based metabolomic analysis of polar and non-polar earthworm metabolites after sublethal exposure to phenanthrene. Metabolomics 2013, 9, 44.
| 1H NMR-based metabolomic analysis of polar and non-polar earthworm metabolites after sublethal exposure to phenanthrene.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXhtVymur0%3D&md5=6ed4186c2bb9194b1e836caa1d9534cfCAS |
[18] S. A. E. Brown, A. J. Simpson, M. J. Simpson, 1H NMR metabolomics of earthworm responses to sublethal PAH exposure. Environ. Chem. 2009, 6, 432.
| 1H NMR metabolomics of earthworm responses to sublethal PAH exposure.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhsFSkurnK&md5=9f452ada06b5e8e54415a549d4b91adcCAS |
[19] J. Yuk, M. J. Simpson, A. J. Simpson, Coelomic fluid: a complimentary biological medium to assess sublethal endosulfan exposure using 1H NMR-based earthworm metabolomics. Ecotoxicology 2012, 21, 1301.
| Coelomic fluid: a complimentary biological medium to assess sublethal endosulfan exposure using 1H NMR-based earthworm metabolomics.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XovVWqsr0%3D&md5=61c1312c4a556e689eda8fe39df60ff7CAS | 22451197PubMed |
[20] Test Number 207: Earthworm Acute Toxicity Tests. OECD Guidelines for the Testing of Chemicals, Section 2: Effects on Biotic Systems 1984 (OECD: Paris).
[21] C. Callahan, M. Skirazi, E. Neuhauser, Comparative toxicity of chemicals to earthworms. Environ. Toxicol. Chem. 1994, 13, 291.
| Comparative toxicity of chemicals to earthworms.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2cXhvVCrt7s%3D&md5=b572ad52e4c067d4b75f6c7bebd1b891CAS |
[22] S. A. Brown, A. J. Simpson, M. J. Simpson, Evaluation of sample preparation methods for nuclear magnetic resonance metabolic profiling studies with Eisenia fetida. Environ. Toxicol. Chem. 2008, 27, 828.
| Evaluation of sample preparation methods for nuclear magnetic resonance metabolic profiling studies with Eisenia fetida.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXktFGntLg%3D&md5=59a4d6066f6fe0ba13e460d9b3a54277CAS | 18333692PubMed |
[23] E. Neuhauser, R. Loehr, D. Milligan, M. Malecki, Toxicity of metals to the earthworm Eisenia fetida. Biol. Fertil. Soils 1985, 1, 149.
| Toxicity of metals to the earthworm Eisenia fetida.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL28XksFGqtb0%3D&md5=270a13bc45b8c3adc421a92e8d9b3cf2CAS |
[24] M. J. Mench, V. L. Didier, M. Löffler, A. Gomez, P. Masson, A mimicked in situ remediation study of metal-contaminated soils with emphasis on cadmium and lead. J. Environ. Qual. 1994, 23, 58.
| A mimicked in situ remediation study of metal-contaminated soils with emphasis on cadmium and lead.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2cXltVOnsLk%3D&md5=264cf13bc7499b6f70b7d6c1657be49aCAS |
[25] J. R. McKelvie, J. Yuk, Y. Xu, A. J. Simpson, M. J. Simpson, 1H NMR and GC/MS metabolomics of earthworm responses to sublethal DDT and endosulfan exposure. Metabolomics 2009, 5, 84.
| 1H NMR and GC/MS metabolomics of earthworm responses to sublethal DDT and endosulfan exposure.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXisFSls7g%3D&md5=35339a18ad84c7900a1a53968c26d604CAS |
[26] H. Wu, A. D. Southam, A. Hines, M. R. Viant, High-throughput tissue extraction protocol for NMR- and MS-based metabolomics. Anal. Biochem. 2008, 372, 204.
| High-throughput tissue extraction protocol for NMR- and MS-based metabolomics.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhtlGjtb%2FL&md5=0d4e7d4963abd65fe48d4462afcf07b2CAS | 17963684PubMed |
[27] O. Beckonert, H. C. Keun, T. M. Ebbels, J. Bundy, E. Holmes, J. C. Lindon, J. K. Nicholson, Metabolic profiling, metabolomic and metabonomic procedures for NMR spectroscopy of urine, plasma, serum and tissue extracts. Nat. Protoc. 2007, 2, 2692.
| Metabolic profiling, metabolomic and metabonomic procedures for NMR spectroscopy of urine, plasma, serum and tissue extracts.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhtlSlsr3E&md5=c1692963929bd803633758ce0204dd9cCAS | 18007604PubMed |
[28] P. E. Anderson, D. A. Mahle, T. E. Doom, N. V. Reo, N. J. DelRaso, M. L. Raymer, Dynamic adaptive binning: an improved quantification technique for NMR spectroscopic data. Metabolomics 2011, 7, 179.
| Dynamic adaptive binning: an improved quantification technique for NMR spectroscopic data.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXmtlGlsrs%3D&md5=4b7cb068037861c6bbc6479396499ca9CAS |
[29] F. Dieterle, A. Ross, G. Schlotterbeck, H. Senn, Probabilistic quotient normalization as robust method to account for dilution of complex biological mixtures. Application in 1H NMR metabonomics. Anal. Chem. 2006, 78, 4281.
| Probabilistic quotient normalization as robust method to account for dilution of complex biological mixtures. Application in 1H NMR metabonomics.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XltVCgtro%3D&md5=300974886d38acbb24c37c83f2c45cfeCAS | 16808434PubMed |
[30] M. R. Viant, E. S. Rosenblum, R. S. Tjeerdema, NMR-based metabolomics: a powerful approach for characterizing the effects of environmental stressors on organism health. Environ. Sci. Technol. 2003, 37, 4982.
| NMR-based metabolomics: a powerful approach for characterizing the effects of environmental stressors on organism health.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXntlykt7w%3D&md5=892f32753a654f9dd13dc0ef182c841cCAS | 14620827PubMed |
[31] S. Hellberg, M. Sjostrom, S. Wold, The prediction of bradykinin potentiating potency of pentapeptides. An example of a peptide quantitative structure–activity relationship. Acta Chem. Scand. B 1986, 40b, 135.
| The prediction of bradykinin potentiating potency of pentapeptides. An example of a peptide quantitative structure–activity relationship.Crossref | GoogleScholarGoogle Scholar |
[32] B. M. Beckwith-Hall, J. T. Brindle, R. H. Barton, M. Coen, E. Holmes, J. K. Nicholson, H. Antti, Application of orthogonal signal correction to minimise the effects of physical and biological variation in high-resolution 1H NMR spectra of biofluids. Analyst (Lond.) 2002, 127, 1283.
| Application of orthogonal signal correction to minimise the effects of physical and biological variation in high-resolution 1H NMR spectra of biofluids.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XnsVKjs74%3D&md5=d41b8054da08b129aef028d97f501deeCAS |
[33] A. M. Weljie, R. Dowlatabadi, B. J. Miller, H. J. Vogel, F. R. Jirik, An inflammatory arthritis-associated metabolite biomarker pattern revealed by 1H NMR spectroscopy. J. Proteome Res. 2007, 6, 3456.
| An inflammatory arthritis-associated metabolite biomarker pattern revealed by 1H NMR spectroscopy.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXptVWlurc%3D&md5=17f599dc841fc3741efb2300e047525bCAS | 17696462PubMed |
[34] Y. Benjamini, Y. Hochberg, Controlling the false discovery rate: a practical and powerful approach to multiple testing. J. R. Stat. Soc. B 1995, 57, 289.
[35] Y. Hochberg, Y. Benjamini, More powerful procedures for multiple significance testing. Stat. Med. 1990, 9, 811.
| More powerful procedures for multiple significance testing.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK3M%2FhvFSgsA%3D%3D&md5=dbc3c107761ff6c3a412683983da73b9CAS | 2218183PubMed |
[36] R. Tibshirani, Regression shrinkage and selection via the lasso. J. R. Stat. Soc. B 1996, 58, 267.
[37] J. E. Klaunig, Y. Xu, J. S. Isenberg, S. Bachowski, K. L. Kolaja, J. Jiang, D. E. Stevenson, E. F. Walborg, The role of oxidative stress in chemical carcinogenesis. Environ. Health Perspect. 1998, 106, 289.
| The role of oxidative stress in chemical carcinogenesis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXitlaitbc%3D&md5=d03b824c1cbca9958cc19f941d62c195CAS | 9539021PubMed |
[38] K. Shah, R. G. Kumar, S. Verma, R. Dubey, Effect of cadmium on lipid peroxidation, superoxide anion generation and activities of antioxidant enzymes in growing rice seedlings. Plant Sci. 2001, 161, 1135.
| Effect of cadmium on lipid peroxidation, superoxide anion generation and activities of antioxidant enzymes in growing rice seedlings.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXnvFCltLY%3D&md5=a27099233238861c4f06f77b1ee32d9aCAS |
[39] J. H. Hacker, P. Bannasch, A. Columbano, Effect of lead nitrate on liver carbohydrate enzymes and glycogen content in the rat. Carcinogenesis 1990, 11, 2199.
| Effect of lead nitrate on liver carbohydrate enzymes and glycogen content in the rat.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK3MXlslWktw%3D%3D&md5=90a51316f3d2d894c67b18042856d5dcCAS |
[40] S. Dubey, P. Misra, S. Dwivedi, S. Chatterjee, S. K. Bag, S. Mantri, M. H. Asif, A. Rai, S. Kumar, M. Shri, Transcriptomic and metabolomic shifts in rice roots in response to CrVI stress. BMC Genomics 2010, 11, 648.
| Transcriptomic and metabolomic shifts in rice roots in response to CrVI stress.Crossref | GoogleScholarGoogle Scholar | 21092124PubMed |
[41] V. Sivapiriya, S. Venkatraman, Effects of dimethoate (O,O-dimethyl-S-methylcarbamoyl methyl phosphorodithioate) and ethanol in antioxidant status of liver and kidney of experimental mice. Pestic. Biochem. Physiol. 2006, 85, 115.
| Effects of dimethoate (O,O-dimethyl-S-methylcarbamoyl methyl phosphorodithioate) and ethanol in antioxidant status of liver and kidney of experimental mice.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XksVOjtL4%3D&md5=dd79f3c66d7a5139be34e4e9b750cf3cCAS |
[42] B. S. Somashekar, P. Kamarajan, T. Danciu, T. L. Kapila, A. M. Chinnaiyan, T. M. Rajendiran, A. Ramamoorthy, Magic angle spinning NMR-based metabolic profiling of head and neck squamous cell carcinoma tissues. J. Proteome Res. 2011, 10, 5232.
| Magic angle spinning NMR-based metabolic profiling of head and neck squamous cell carcinoma tissues.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhtlaqtrnI&md5=b37044f3bb446a1864fce4ec3e315079CAS | 21961579PubMed |
[43] T. Wei, Y. Ni, J. Hou, C. Chen, B. Zhao, W. Xin, Hydrogen peroxide-induced oxidative damage and apoptosis in cerebellar granule cells: protection by Ginkgo biloba extract. Pharmacol. Res. 2000, 41, 427.
| Hydrogen peroxide-induced oxidative damage and apoptosis in cerebellar granule cells: protection by Ginkgo biloba extract.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXhsFSqtLc%3D&md5=f4dc636eb18e7c6d97cea20af3fc4668CAS | 10704267PubMed |
[44] R. W. Ansari, R. K. Shukla, R. S. Yadav, K. Seth, A. B. Pant, D. Singh, A. K. Agrawal, F. Islam, V. K. Khanna, Cholinergic dysfunctions and enhanced oxidative stress in the neurobehavioral toxicity of lambda-cyhalothrin in developing rats. Neurotox. Res. 2012, 22, 292.
| Cholinergic dysfunctions and enhanced oxidative stress in the neurobehavioral toxicity of lambda-cyhalothrin in developing rats.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38Xhtl2lsr3L&md5=a62655a9f37b22bed72c711aee147502CAS | 22327935PubMed |
[45] B. Ganesan, S. Buddhan, R. Anandan, R. Sivakumar, R. AnbinEzhilan, Antioxidant defense of betaine against isoprenaline-induced myocardial infarction in rats. Mol. Biol. Rep. 2010, 37, 1319.
| Antioxidant defense of betaine against isoprenaline-induced myocardial infarction in rats.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhtlajtbs%3D&md5=2e4e2042216b7d9ac786cebe2403b4d6CAS | 19288277PubMed |
[46] K. K. Kharbanda, M. E. Mailliard, C. R. Baldwin, H. C. Beckenhauer, M. F. Sorrell, D. J. Tuma, Betaine attenuates alcoholic steatosis by restoring phosphatidylcholine generation via the phosphatidylethanolamine methyltransferase pathway. J. Hepatol. 2007, 46, 314.
| Betaine attenuates alcoholic steatosis by restoring phosphatidylcholine generation via the phosphatidylethanolamine methyltransferase pathway.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhslyltQ%3D%3D&md5=1e5867fc9dbb0777b5b91c25ab3940f2CAS | 17156888PubMed |
[47] S. A. Craig, Betaine in human nutrition. Am. J. Clin. Nutr. 2004, 80, 539.
| 1:CAS:528:DC%2BD2cXnsVWitbc%3D&md5=02ad198c1979c5b963b5ff667fdc841bCAS | 15321791PubMed |
[48] J. G. Bundy, J. K. Sidhu, F. Rana, D. J. Spurgeon, C. Svendsen, J. F. Wren, S. R. Sturzenbaum, A. J. Morgan, P. Kille, ‘Systems toxicology’ approach identifies coordinated metabolic responses to copper in a terrestrial non-model invertebrate, the earthworm Lumbricus rubellus. BMC Biol. 2008, 6, 25.
| ‘Systems toxicology’ approach identifies coordinated metabolic responses to copper in a terrestrial non-model invertebrate, the earthworm Lumbricus rubellus.Crossref | GoogleScholarGoogle Scholar | 18522721PubMed |
[49] J. G. Bundy, H. C. Keun, J. K. Sidhu, D. J. Spurgeon, C. Svendsen, P. Kille, A. J. Morgan, Metabolic profile biomarkers of metal contamination in a sentinel terrestrial species are applicable across multiple sites. Environ. Sci. Technol. 2007, 41, 4458.
| Metabolic profile biomarkers of metal contamination in a sentinel terrestrial species are applicable across multiple sites.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXltVKqs70%3D&md5=00426ed84836af6574de65998e7692c6CAS | 17626452PubMed |
[50] J. G. Bundy, E. M. Lenz, N. J. Bailey, C. L. Gavaghan, C. Svendsen, D. Spurgeon, P. Hankard, D. Osborn, J. M. Weeks, S. A. Trauger, Metabonomic assessment of toxicity of 4‐fluoroaniline, 3, 5‐difluoroaniline and 2‐fluoro‐4‐methylaniline to the earthworm Eisenia veneta (Rosa): identification of new endogenous biomarkers. Environ. Toxicol. Chem. 2002, 21, 1966.
| Metabonomic assessment of toxicity of 4‐fluoroaniline, 3, 5‐difluoroaniline and 2‐fluoro‐4‐methylaniline to the earthworm Eisenia veneta (Rosa): identification of new endogenous biomarkers.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38Xmt12jtL4%3D&md5=e3275f13bcd26347f455c55afa5352f9CAS | 12206438PubMed |
[51] Q. Guo, J. K. Sidhu, T. M. D. Ebbels, F. Rana, D. J. Spurgeon, C. Svendsen, S. R. Stürzenbaum, P. Kille, A. J. Morgan, J. G. Bundy, Validation of metabolomics for toxic mechanism of action screening with the earthworm Lumbricus rubellus. Metabolomics 2009, 5, 72.
| Validation of metabolomics for toxic mechanism of action screening with the earthworm Lumbricus rubellus.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXisFSlsrg%3D&md5=b8a0fba212acbdf85d7cf87324fcbd8eCAS |
[52] S. J. Rochfort, V. Ezernieks, A. L. Yen, NMR-based metabolomics using earthworms as potential indicators for soil health. Metabolomics 2009, 5, 95.
| NMR-based metabolomics using earthworms as potential indicators for soil health.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXisFSlsrY%3D&md5=4a13d48512d9fd8b4a9a4001fe5b965aCAS |
[53] R. Franco, R. Sánchez-Olea, E. M. Reyes-Reyes, M. I. Panayiotidis, Environmental toxicity, oxidative stress and apoptosis: ménage a trois. Mutat. Res. Genet. Toxicol. Environ. Mutagen. 2009, 674, 3.
| Environmental toxicity, oxidative stress and apoptosis: ménage a trois.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXjtF2htLo%3D&md5=f8f96369c5f25fb777562451d50d57ddCAS |
[54] I. Baranowska-Bosiacka, I. Gutowska, C. Marchetti, M. Rutkowska, M. Marchlewicz, A. Kolasa, A. Prokopowicz, I. Wiernicki, K. Piotrowska, M. Baśkiewicz, Altered energy status of primary cerebellar granule neuronal cultures from rats exposed to lead in the pre- and neonatal period. Toxicology 2011, 280, 24.
| Altered energy status of primary cerebellar granule neuronal cultures from rats exposed to lead in the pre- and neonatal period.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhs1ajsrjN&md5=1d2a9af0dc76a3943d80cea11ffd2417CAS | 21108985PubMed |
[55] S. A. Jones, M. Jorgensen, F. Z. Chowdhury, R. Rodgers, J. Hartline, M. P. Leatham, C. Struve, K. A. Krogfelt, P. S. Cohen, T. Conway, Glycogen and maltose utilization by Escherichia coli O157:H7 in the mouse intestine. Infect. Immun. 2008, 76, 2531.
| Glycogen and maltose utilization by Escherichia coli O157:H7 in the mouse intestine.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXms1egu7Y%3D&md5=a977ecc1cae5136f73188b1af7f93403CAS | 18347038PubMed |
[56] B. P. Lankadurai, D. M. Wolfe, A. J. Simpson, M. J. Simpson, 1H NMR-based metabolomic observation of a two-phased toxic mode of action in Eisenia fetida after sublethal phenanthrene exposure. Environ. Chem. 2011, 8, 105.
| 1H NMR-based metabolomic observation of a two-phased toxic mode of action in Eisenia fetida after sublethal phenanthrene exposure.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXmt1yju7k%3D&md5=3748a9d66cdb726f2d7af5916d6c7620CAS |
[57] M. L. Whitfield Åslund, A. J. Simpson, M. J. Simpson, 1H NMR metabolomics of earthworm responses to polychlorinated biphenyl (PCB) exposure in soil. Ecotoxicology 2011, 20, 836.
| 1H NMR metabolomics of earthworm responses to polychlorinated biphenyl (PCB) exposure in soil.Crossref | GoogleScholarGoogle Scholar | 21424327PubMed |
[58] J. G. Bundy, D. J. Spurgeon, C. Svendsen, P. K. Hankard, J. M. Weeks, D. Osborn, J. C. Lindon, J. K. Nicholson, Environmental metabonomics: applying combination biomarker analysis in earthworms at a metal-contaminated site. Ecotoxicology 2004, 13, 797.
| Environmental metabonomics: applying combination biomarker analysis in earthworms at a metal-contaminated site.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXhslyrs7o%3D&md5=93b3dc02f14e23f4597f20ae87d9911aCAS | 15736850PubMed |
[59] E. M. Lenz, J. M. Weeks, J. C. Lindon, D. Osborn, J. K. Nicholson, Qualitative high field 1H-NMR spectroscopy for the characterization of endogenous metabolites in earthworms with biochemical biomarker potential. Metabolomics 2005, 1, 123.
| Qualitative high field 1H-NMR spectroscopy for the characterization of endogenous metabolites in earthworms with biochemical biomarker potential.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28Xht1SmsrjK&md5=1da69e1b7558848d19ddbe6b317b2ed1CAS |
[60] G. Flora, D. Gupta, A. Tiwari, Toxicity of lead: a review with recent updates. Interdiscip. Toxicol. 2012, 5, 47.
| Toxicity of lead: a review with recent updates.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhvVKqs7jM&md5=8a3e5c54c78b874015297de31a257b59CAS | 23118587PubMed |
[61] S. Lasley, M. Gilbert, Rat hippocampal glutamate and GABA release exhibit biphasic effects as a function of chronic lead exposure level. Toxicol. Sci. 2002, 66, 139.
| Rat hippocampal glutamate and GABA release exhibit biphasic effects as a function of chronic lead exposure level.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XitVegur8%3D&md5=7d312a3d08f60d850d3a655fac3bb4d4CAS | 11861981PubMed |
[62] C. Xiao, Y. Gu, C.-Y. Zhou, L. Wang, M.-M. Zhang, D.-Y. Ruan, Pb2+ impairs GABAergic synaptic transmission in rat hippocampal slices: a possible involvement of presynaptic calcium channels. Brain Res. 2006, 1088, 93.
| Pb2+ impairs GABAergic synaptic transmission in rat hippocampal slices: a possible involvement of presynaptic calcium channels.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XkvVygt7k%3D&md5=f2d8fcae1e652f277a8a8de2e7f9da9bCAS | 16630593PubMed |
[63] A. Shafy, V. Molinié, M. Cortes-Morichetti, V. Hupertan, N. Lila, J. C. Chachques, Comparison of the effects of adenosine, inosine, and their combination as an adjunct to reperfusion in the treatment of acute myocardial infarction. ISRN Cardiol. 2012, 2012, 326809.
| Comparison of the effects of adenosine, inosine, and their combination as an adjunct to reperfusion in the treatment of acute myocardial infarction.Crossref | GoogleScholarGoogle Scholar | 22462024PubMed |
[64] J. Xia, D. S. Wishart, MetPA: a web-based metabolomics tool for pathway analysis and visualization. Bioinformatics 2010, 26, 2342.
| MetPA: a web-based metabolomics tool for pathway analysis and visualization.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhtFGhu77I&md5=cf26a341e2d79e515edc040a02f5d1b5CAS | 20628077PubMed |
