Environmental Science and Pollution Research

, Volume 26, Issue 18, pp 18181–18190 | Cite as

Metabonomic analysis of the hepatic injury suffer from hexavalent chromium poisoning in broilers

  • Yali Zhao
  • Hui Zhang
  • Xiaoxing Wu
  • Tianguang Zhang
  • Ke Shen
  • Lei Li
  • Yuxuan Peng
  • Khalid Mehmood
  • Donghai ZhouEmail author
Research Article


Chromium is used in daily life and has a wide range of functions. It plays an important role in protein synthesis and carbohydrate and lipid metabolism. Chromium is found in trivalent Cr(III) and hexavalent Cr(VI) form; Cr(III) is relatively stable and intimately participates with many phenomena of metabolisms. Whereas, Cr(VI) is toxic, which results in growth inhibition and leading to changes in components of antioxidant systems as well as secondary metabolites. However, the molecular mechanism that is involved in Cr (VI)-induced hepatotoxicity is still unclear. For this purpose, 40 chickens were randomly assigned into two groups: the normal group (feeding the basic diet and clear water), the chromium group (16%LD50, 74.24 mg/kg/day K2Cr2O7). The samples were subjected to pathological examination and UHPLC-QE-MS non-target metabolomics method for metabolomics analysis of broiler liver using principal component analysis (PCA) and partial least squares discriminant analysis (OPLS-DA). The central venous cells of the broiler liver in the chromium poisoning group showed turbidity and flaky necrosis, nuclear condensation, nuclear rupture, and even nuclear dissolution. The differential metabolite analysis between the chromium poisoning and the control group showed that 32 differential metabolites were upregulated and 15 were downregulated in positive ion mode. Whereas,17 differential metabolites were downregulated, and 35 were downregulated in negative ion mode (P ≤ 0.05). The potential marker substances are oleic acidamide, farnesylacetone, betaine, taurine, choline, and galactinol. Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways showed that the lipid metabolism, carbohydrate metabolism, nucleotide metabolism, amino acid metabolism, energy metabolism, membrane transport, digestive system, and nervous system were the most important metabolic pathways in the liver. This study provides a theoretical basis for the future understanding of the pathogenesis of chromium poisoning and a new insight of the subsequent molecular mechanism of chromium hepatotoxicity.


Chromium poisoning UHPLC-QE-MS metabolomics Metabolites Hepatotoxicity Differential metabolites 


Author contributions

Y.Z., X.W., H.Z., T.Z., K.S., L.L., K.M., Y.P., and D.Z. were responsible for study conception and design; H.Z. and K.M. were involved in the drafting of the manuscript.

Funding information

This study was supported by the National Key R&D Program of China (2016YFD0501208), National Natural Science Foundation of China (no. 30700588), and Hubei Provincial Natural Science Foundation of China (grant no. 2014CFB244).

Compliance with ethical standards

All the experiments were performed after the approval of the Institutional Animal Welfare and Research Ethics Committee of Huazhong Agricultural University Wuhan, China (approval no. 31272556). All animal experiments and methods were conducted under the relevant procedure of Proclamation of the Standing Committee of Hubei People’s Congress (no. 29), China.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

11356_2019_5075_MOESM1_ESM.docx (12 kb)
ESM 1 (DOCX 12 kb)


  1. Anandasadagopan SK, Sundaramoorthy C (2017) S-Allyl cysteine alleviates inflammation by modulating the expression of NF-κB during chromium (VI)-induced hepatotoxicity in rats. Hum Exp Toxicol 36(11):1186–1200CrossRefGoogle Scholar
  2. Chang Z, Zhang H, Mehmood K, Luo M, Zhao Y, Nabi F (2018) Effect of nano copper on visceral organs and the contents of trace elements in weanling pigs. Toxin Rev:11:1–11:6.
  3. Chen P, Zhu Y, Wan H, Wang Y, Hao P, Cheng Z (2017) Effects of the oral administration of K2Cr2O7 and Na2SeO3 on Ca, Mg, Mn, Fe, Cu, and Zn contents in the heart, liver, spleen, and kidney of chickens. Biol Trace Elem Res 180(2):285–296CrossRefGoogle Scholar
  4. Chena YE, Maoa HT, Maa J (2017) Biomonitoring chromium III or VI soluble pollution by moss chlorophyll fluorescence. Chemosphere 11:177Google Scholar
  5. Chundawat RS, Sood PP (2005) Vitamins deficiency in developing chick during chromium intoxication and protection thereof. Toxicology 211:124–131CrossRefGoogle Scholar
  6. Hsinhui K, Hseinchi W, Kuansheng C, Weiming L (2016) Trivalent chromium attenuated corticosterone secretion and actions in adrenocorticotropic hormone-stimulated rats. Pak Vet J 36:41–44Google Scholar
  7. Jeyasingh JP (2005) Bioremediation of chromium contaminated soil optimization of operating parameters under laboratory conditions [J]. J Hazard Mater 118:113–116CrossRefGoogle Scholar
  8. Lin TJ, Huang YL, Chang JS (2018) Optimal dosage and early intervention of l-ascorbic acid inhibiting KCrO-induced renal tubular cell damage. J Trace Elem Med Biol 48:1–7. CrossRefGoogle Scholar
  9. Liu XT, Rehman MU, Mehmood K, Huang S, Tian XX, Wu XX (2018a) Ameliorative effects of nano-elemental selenium against hexavalent chromium-induced apoptosis in broiler liver. Environ Sci Pollut R 25(16):15609–15615CrossRefGoogle Scholar
  10. Liu XT, Rehman MU, Zhang H, Tian X, Wu XX (2018b) Protective effects of nano-elemental selenium against chromium-vi-induced oxidative stress in broiler liver. J Biol Regul Homeost Agents 32(1):47Google Scholar
  11. Luo H, Li K, Weng S, Bai Y, Zhang H, Mehmood K, Shahzad M, Wang J (2018) Assessment of serum trace elements in thiram induced tibial dyschondroplasia chickens. Pak Vet J 38:101–104CrossRefGoogle Scholar
  12. Ma QQ, Chen Q, Shen ZH, Li DL, Han T, Qin JG, Chen LQ, Du ZY (2017) The metabolomics responses of Chinese mitten-hand crab (Eriocheir sinensis) to different dietary oils. Aquaculture 479:188–189CrossRefGoogle Scholar
  13. McKillop AM, Flatt PR (2011) Emerging applications of metabolomic and genomic profiling in diabetic clinical medicine. Diabetes Care 34:2624–2630CrossRefGoogle Scholar
  14. Nishiumi S, Kohata T, Kobayashi T, Kodama Y, Ohtsuki S, Yoshida M (2019) Comparison of venous and fingertip plasma using non-targeted proteomics and metabolomics. Talanta 192:182–188. CrossRefGoogle Scholar
  15. NRC (National Research Council) (2001) Nutrient requirements of poultry, 9th Rev. In: Ed. National Academy Press, Washington DCGoogle Scholar
  16. Plumb R, Castro-Perez J, Granger J (2004) Ultra-performance liquid chromatography coupled to quadrupole-orthogonal time-of-flight mass sepctrometry. Rapid Commun Mass Spectrom 18(19):2331–2337CrossRefGoogle Scholar
  17. Saccenti E, Hoefsloot HCJ, Smilde AK (2014) Reflections on univariate and multivariate analysis of metabolomics data. Metabolomics 10(3):361–374CrossRefGoogle Scholar
  18. Saeed AA, Sandhu MA, Khilji MS, Yousaf MS, Rehman HU, Tanvir ZI (2017) Effects of dietary chromium supplementation on muscle and bone mineral interaction in broiler chicken. J Trace Elem Med Biol 42:25–29CrossRefGoogle Scholar
  19. Sahin N, Hayirli A, Orhan C, Tuzcu M, Akdemir F, Komorowski JR (2017) Effects of the supplemental chromium form on performance and oxidative stress in broilers exposed to heat stress. Poult Sci 96(12):4317–4324. CrossRefGoogle Scholar
  20. Shah SH, Kraus WE, Newgard CB (2012) Metabolomic profiling for the identification of novel biomarkers and mechanisms related to common cardiovascular diseases form and function. Circulation 126:1110–1120CrossRefGoogle Scholar
  21. Smith CA, Want EJ, O’Maille G, Abagyan R, Siuzdak G (2006) Xcms: processing mass spectrometry data for metabolite profiling using nonlinear peak alignment, matching, and identification. Anal Chem 78(3):779–787CrossRefGoogle Scholar
  22. Theodoridis G, Gika HG, Wilson ID (2008) LC-MS-based methodology for global metabolite profliling in metabonomics/metabolomics. TrAC Ttends in Anal Chem 27(3):251–260CrossRefGoogle Scholar
  23. Tian X, Zhang H, Zhao Y, Mehmood K, Wu X, Chang Z, Luo M, Liu X, Ijaz M, Javed MT, Zhou D (2018) Transcriptome analysis reveals the molecular mechanism of hepatic metabolism disorder caused by chromium poisoning in chickens. Environ Sci Pollut Res 25(16):15411–15421CrossRefGoogle Scholar
  24. Wan H, Zhu Y, Chen P, Wang Y, Hao P, Cheng Z (2017) Effect of various selenium doses on chromium(iv)-induced nephrotoxicity in a male chicken model. Chemosphere 174:306–314CrossRefGoogle Scholar
  25. Wang J, Zhang T, Shen X (2016) Serum metabolomics for early diagnosis of esophageal squamous cell carcinoma by UHPLC-QTOF/MS. Metabolomics 12(7):116CrossRefGoogle Scholar
  26. Wang Y, Liu Y, Wan H, Zhu Y, Chen P, Hao P (2017) Moderate selenium dosing inhibited chromium (vi) toxicity in chicken liver. J Biochem Mol Toxicol 31(8):e21916CrossRefGoogle Scholar
  27. White PE, Vincent JB (2018) Systematic review of the effects of chromium(iii) on chickens. Biol Trace Elem Res.
  28. Wilson ID, Nicholson JK, Castro-Perez J (2005) High resolution “ultra performance”liquid chromatography coupled to OA-TOF mass sepctrometry as a tool for differential metabolic pathway profiling in functional genomic studies. J Proteome Res 4(2):591–598CrossRefGoogle Scholar
  29. Worley B, Powers R (2013) Multivariate analysis in metabolomics. Current Metabolomics 1(1):92–107Google Scholar
  30. Wu J, Cheng J (2009) Explore the effects of hexavalent chromium on human health and preventive measures. Modern preventive medicine 36(24):4610–4616Google Scholar
  31. Wu X, Li A, Zhang H, Mehmood K, Zhao Y, Luo M (2018) Study on the hepatic injury induced by hexavalent chromium in chickens. Int J Agric Biol 20:1641–1644Google Scholar
  32. Zhang H, Wu X, Mehmood K, Chang Z, Li K, Jiang X, Nabi F, Ijaz M, Rehman MU, Javed MT, Zhou D (2017a) Intestinal epithelial cell injury induced by copper containing nanoparticles in piglets. Environ Toxicol Pharmacol 56:151–156CrossRefGoogle Scholar
  33. Zhang X, Tong J, Hu BX, Wei W (2017b) Adsorption and desorption for dynamics transport of hexavalent chromium (Cr(vi)) in soil column. Environ Sci Pollut R 25(5):1–10Google Scholar
  34. Zhang H, Chang Z, Mehmood K, Abbas RZ, Nabi F, Rehman MU, Wu X, Tian X, Yuan X, Li Z, Zhou D (2018) Nano copper induces apoptosis in PK-15 cells via a mitochondria-mediated pathway. Biol Trace Elem Res 181(1):62–70CrossRefGoogle Scholar
  35. Zhu Q (2013) How is our body detoxified[J]. Biol Bull 48(07):13–19Google Scholar
  36. Zhu ZJ, Schultz AW, Wang J (2013) Liquid chromatography quadrupole time-of-flight mass spectrometry characterization of metabolites guided by the METLIN database. Nat Protoc 8(3):451–460CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Yali Zhao
    • 1
  • Hui Zhang
    • 1
    • 2
  • Xiaoxing Wu
    • 1
  • Tianguang Zhang
    • 1
  • Ke Shen
    • 1
  • Lei Li
    • 1
  • Yuxuan Peng
    • 1
  • Khalid Mehmood
    • 1
    • 3
  • Donghai Zhou
    • 1
    Email author
  1. 1.College of Veterinary MedicineHuazhong Agricultural UniversityWuhanP.R. China
  2. 2.College of Veterinary MedicineCornell UniversityIthacaUSA
  3. 3.University College of Veterinary and Animal SciencesIslamia University of BahawalpurBahawalpurPakistan

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