Skip to main content

Advertisement

SpringerLink
Log in

Acute exposure to microcystin-LR induces hepatopancreas toxicity in the Chinese mitten crab (Eriocheir sinensis)

  • Biologics
  • Published:
Archives of Toxicology Aims and scope Submit manuscript

Abstract

The Chinese mitten crab is an important economic species in the Chinese aquaculture industry due to its rich nutritional value and distinct flavor. The hepatopancreas is a popular edible part of the Chinese mitten crab, and therefore, hepatopancreatic health directly determines its quality. However, a large-scale outbreak of hepatopancreatic necrosis syndrome (“Shuibiezi” disease in Chinese), which is caused by abiotic agents correlated with cyanobacteria bloom outbreaks, adversely affects the Chinese mitten crab breeding industry. Cyanobacterial blooms that occur in high-density farming ponds can produce microcystin-LR (MC-LR), which is hepatotoxic in fish and mammals. Hepatopancreas toxicity of MC-LR (0, 25, 50 and 75 μg/kg) was investigated after 48 h of exposure. The MC-LR can cause hepatopancreatic injury by inducing hepatopancreatic structural damage, subcellular structural changes, and cell apoptosis, followed by enhanced lipid peroxidase, reactive oxygen species, and apoptosis-related enzyme (Caspase 3, 8, and 9) activities. These in turn promote gene and protein expression of apoptosis-associated proteases (Caspase 3, 7, and 8, Bcl-2, and Bax), and alter antioxidant system responses (superoxide dismutase, glutathione S-transferase, glutathione peroxidase, glutathione reductase activities, and glutathione content). The present study is the first report on MC-LR hepatotoxicity in the Chinese mitten crab and confirms hepatopancreas toxicity, providing a theoretical basis for enhancing MCs resistance and developing preventive and curative measures against hepatopancreatic disease in the Chinese mitten crab breeding industry.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12

Similar content being viewed by others

References

  • Baganz D, Staaks G, Steinberg C (1998) Impact of the cyanobacteria toxin, microcystin-LR on behaviour of zebrafish, Danio rerio. Water Res 32:948–952

    Article  CAS  Google Scholar 

  • Boaru DA, Dragoş N, Schirmer K (2006) Microcystin-LR induced cellular effects in mammalian and fish primary hepatocyte cultures and cell lines: a comparative study. Toxicology 218:134–148

    Article  CAS  PubMed  Google Scholar 

  • Bouaicha N, Maatouk I (2004) Microcystin-LR and nodularin induce intracellular glutathione alteration, reactive oxygen species production and lipid peroxidation in primary cultured rat hepatocytes. Toxicol Lett 148:53–63

    Article  CAS  PubMed  Google Scholar 

  • Campos A, Vasconcelos V (2010) Molecular mechanisms of microcystin toxicity in animal cells. Int j Mol Sci 11:268–287

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carmichael W (1992) Cyanobacteria secondary metabolites—the cyanotoxins. J Appl Bacteriol 72:445–459

    Article  CAS  PubMed  Google Scholar 

  • Chen T, Wang Q, Cui J, Yang W, Shi Q, Hua Z, Ji J, Shen P (2005) Induction of apoptosis in mouse liver by microcystin-LR: a combined transcriptomic, proteomic, and simulation strategy. Mol Cell Proteom 4:958–974

    Article  CAS  Google Scholar 

  • Chen YY, Chang L, Huang XH (2015) Effects of microcystin on activities of immune enzymes in the White Shrimp Litopenaeus Vannamei. J Zhanjiang Ocean Univ 35:35–39

    Google Scholar 

  • Chi C, Giri S, Jun J, Kim H, Yun S, Kim S, Park S (2016) Marine toxin okadaic acid affects the immune function of bay scallop (Argopecten irradians). Molecules 21:1108

    Article  PubMed Central  Google Scholar 

  • Dey P (2018) Frozen section: principle and procedure. Basic Adv Lab Tech Histopathol Cytolo:51–55.

  • Ding WI, Shen HI, Ong CA (2000) Critical role of reactive oxygen species and mitochondrial permeability transition in microcystin-induced rapid apoptosis in rat hepatocytes. Hepatology 32:547–555

    Article  CAS  PubMed  Google Scholar 

  • Earnshaw WC, Martins LM, Kaufmann SH (1999) Mammalian caspases: structure, activation, substrates, and functions during apoptosis. Annu Rev Biochem 68:383–424

    Article  CAS  PubMed  Google Scholar 

  • Gehringer MM, Downs KS, Downing TG, Naudé RJ, Shephard EG (2003) An investigation into the effect of selenium supplementation on microcystin hepatotoxicity. Toxicon 41:451–458

    Article  CAS  PubMed  Google Scholar 

  • Ghobrial MG, Nassr HS, Kamil AW (2015) Bioactivity effect of two macrophyte extracts on growth performance of two bloom-forming cyanophytes. Egypt J Aquat Res 41:69–81

    Article  Google Scholar 

  • Guo X, Chen L, Chen J, Xie P, Zeng C (2015) Quantitatively evaluating detoxification of the hepatotoxic microcystin-LR through the glutathione (GSH) pathway in SD rats. Environ Sci Pollut Res 22:19273–19284

    Article  CAS  Google Scholar 

  • Gupta N, Pant S, Vijayaraghavan R, Rao PL (2003) Comparative toxicity evaluation of cyanobacterial cyclic peptide toxin microcystin variants (LR, RR, YR) in mice. Toxicology 188:285–296

    Article  CAS  PubMed  Google Scholar 

  • Haan JBD, Cristiano F, Iannello RC, Kola I (1995) Cu/Zn-superoxide dismutase and glutathione peroxidase during aging. Biochem Mol Biol Int 35:1281–1297

    PubMed  Google Scholar 

  • He J, Chen J, Xie P, Zhang D, Li G, Wu L, Zhang W, Guo X, Li S (2012) Quantitatively evaluating detoxification of the hepatotoxic microcystins through the glutathione and cysteine pathway in the cyanobacteria-eating bighead carp. Aquat Toxicol 116–117:61–68

    Article  PubMed  Google Scholar 

  • He X, Sun J, Huang X (2018) Expression of caspase-3, Bax and Bcl-2 in hippocampus of rats with diabetes and subarachnoid hemorrhage. Exp Ther Med 15:873–877

    CAS  PubMed  Google Scholar 

  • Hou J, Li L, Xue T, Long M, Su Y, Wu N (2015) Hepatic positive and negative antioxidant responses in zebrafish after intraperitoneal administration of toxic microcystin-LR. Chemosphere 120:729–736

    Article  CAS  PubMed  Google Scholar 

  • Jacquet C, Thermes V, de Luze A, Puiseux-Dao S, Bernard C, Joly JS, Bourrat F, Edery M (2004) Effects of microcystin-LR on development of medaka fish embryos (Oryzias latipes). Toxicon 43:141–147

    Article  CAS  PubMed  Google Scholar 

  • Jayaraj R, Anand T, Rao PVL (2006) Activity and gene expression profile of certain antioxidant enzymes to microcystin-LR induced oxidative stress in mice. Toxicology 220:136–146

    Article  CAS  PubMed  Google Scholar 

  • Kabel AM (2014) Free radicals and antioxidants: role of enzymes and nutrition. World j Nutr Health 2:35–38

    Google Scholar 

  • Klaunig JE, Xu Y, Isenberg JS, Bachowski S, Kolaja KL, Jiang J, Stevenson DE, Walborg EF Jr (1998) The role of oxidative stress in chemical carcinogenesis. Environ Health Perspect 106:289–295

    CAS  PubMed  PubMed Central  Google Scholar 

  • Krishnan A, Koski G, Mou X (2019) Characterization of microcystin-induced apoptosis in HepG2 hepatoma cells. Toxicon 173:20–26

    Article  PubMed  Google Scholar 

  • Li G, Xie P, Fu J, Hao L, Xiong Q (2008) Microcystin-induced variations in transcription of GSTs in an omnivorous freshwater fish, goldfish. Aquat Toxicol 88:75–80

    Article  CAS  PubMed  Google Scholar 

  • Li L, Xie P, Guo L (2010) Antioxidant response in liver of the phytoplanktivorous bighead carp (Aristichthys nobilis) intraperitoneally-injected with extracted microcystins. Fish Physiol Biochem 36:165–172

    Article  CAS  PubMed  Google Scholar 

  • Li XB, Zhang X, Ju J, Li Y, Yin L, Pu Y (2015) Maternal repeated oral exposure to microcystin-LR affects neurobehaviors in developing rats. Environ Toxicol Chem 34:64–69

    Article  PubMed  Google Scholar 

  • Li S, Chen J, Xie P, Guo X, Fan H, Yu D, Zeng C, Chen L (2016) The role of glutathione detoxification pathway in MCLR-induced hepatotoxicity in SD rats. Environ Toxicol 30:1470–1480

    Article  Google Scholar 

  • Liu LP, Su XM, Chen TY, Li K, Zhan J, Egna H, Diana J (2016) Evidence of rapid transfer and bioaccumulation of microcystin-LR poses potential risk to freshwaterprawn Macrobrachium rosenbergii (deMan). Aquac Res 47:1–10

    Article  Google Scholar 

  • Liu JD, Liu WB, Zhang CY, Xu CY, Zheng XC, Zhang DD, Chi C (2020) Dietary glutathione supplementation enhances antioxidant activity and protects against lipopolysaccharide-induced acute hepatopancreatic injury and cell apoptosis in Chinese mitten crab, Eriocheir Sinensis. Fish Shellfish Immunol 97:440–454

    Article  CAS  PubMed  Google Scholar 

  • Macdonald J, Galley HF, Webster NR (2003) Oxidative stress and gene expression in sepsis. Br J Anaesth 90:221–232

    Article  CAS  PubMed  Google Scholar 

  • Mattos L, Valença S, Azevedo S, Soares R (2014) Dualistic evolution of liver damage in mice triggered by a single sublethal exposure to Microcystin-LR. Toxicon 83:43–51

    Article  CAS  PubMed  Google Scholar 

  • Maurits A, Jannie A, Ulrich S (2002) Electrical, contractile and structural remodeling during atrial fibrillation. Cardiovasc Res 54:230–246

    Article  Google Scholar 

  • Moreno I, Pichardo S, Jos A, Gómez-Amores L, Mate A, Vazquez CM, Cameán AM (2005) Antioxidant enzyme activity and lipid peroxidation in liver and kidney of rats exposed to microcystin-LR administered intraperitoneally. Toxicon 45:395–402

    Article  CAS  PubMed  Google Scholar 

  • Pflugmacher S, Wiegand C, Oberemm A, Beattie KA, Krause E, Codd GA, Steinberg CE (1998) Identification of an enzymatically formed glutathione conjugate of the cyanobacterial hepatotoxin microcystin-LR: the first step of detoxication. Biochim Biophys Acta-Gen Subj 1425:527–533

    Article  CAS  Google Scholar 

  • Pietsch C, Wiegand C, Ame MV, Nicklisch A, Wunderlin D, Pflugmacher S (2001) The effects of cyanobacterial crude extract on different aquatic organisms: evidence for cyanobacterial toxin modulating factors. Environ Toxicol 16:535–542

    Article  CAS  PubMed  Google Scholar 

  • Pinho G, Rosa C, Maciel FE, Bianchini A, Yunes JS, Proenca LAO, Monserrat JM (2005) Antioxidant responses and oxidative stress after microcystin exposure in the hepatopancreas of an estuarine crab species. Ecotox Environ Safe 61:353–360

    Article  CAS  Google Scholar 

  • Qiao Q, Djediat C, Huet H, Duval C, Le Manach S, Bernard C, Edery M, Marie B (2019) Subcellular localization of microcystin in the liver and the gonads of medaka fish acutely exposed to microcystin-LR. Toxicon 159:14–21

    Article  CAS  PubMed  Google Scholar 

  • Rao P, Bhattacharya R, Pant S, Bhaskar A (1995) Toxicity evaluation of in vitro cultures of freshwater cyanobacterium Microcystis aeruginosa: I. Hepatotoxic and histopathological effects in rats. Biomed Environ Sci 8:254–264

    CAS  PubMed  Google Scholar 

  • Sabatini SE, Brena BM, Pirez M, de Molina MDR, Luquet CM (2015) Oxidative effects and toxin bioaccumulation after dietary microcystin intoxication in the hepatopancreas of the crab Neohelice (Chasmagnathus) granulata. Ecotox Environ Safe 120:136–141

    Article  CAS  Google Scholar 

  • Scoltock AB, Cidlowski JA (2004) Activation of intrinsic and extrinsic pathways in apoptotic signaling during UV-C-induced death of Jurkat cells: the role of caspase inhibition. Exp Cell Res 297:212–223

    Article  CAS  PubMed  Google Scholar 

  • Shin EJ, Hwang YG, Pham DT, Lee JW, Lee YJ, Pyo D, Lei XG, Jeong JH, Kim HC (2018) Genetic overexpression of glutathione peroxidase-1 attenuates microcystin-leucine-arginine-induced memory impairment in mice. Neurochem Int 118:152–162

    Article  CAS  PubMed  Google Scholar 

  • Sun SM, Zheng C, Shi XT (2021) Effect of paternal exposure to microcystin-LR on testicular dysfunction, reproduction, and offspring immune response in the oriental river prawn (Macrobrachium nipponense). Aquaculture 534:736332

    Article  CAS  Google Scholar 

  • Svirčev Z, Lalić D, Bojadžija Savić G, Tokodi N, Backović DD, Chen L, Meriluoto J, Codd GA (2019) Global geographical and historical overview of cyanotoxin distribution and cyanobacterial poisonings. Arch Toxicol 93:2429–2481

    Article  PubMed  Google Scholar 

  • Vinagre T, Alciati JC, Regoli F, Bocchetti R, Yunes JS, Bianchini A, Monserrat JM (2003) Effect of microcystin on ion regulation and antioxidant system in gills of the estuarine crab Chasmagnathus granulatus (Decapoda, Grapsidae). Comp Biochem Physiol C 135:67–75

    CAS  Google Scholar 

  • Wang J, Sun B (2012) Expression of caspase-3 and caspase-9 and their significance in breast cancer. Chin j Clin Exp Pathol 28(378–381):389

    Google Scholar 

  • Wei LL, He L, Fu J, Liu Y, Ruan J, Liu L, Zhong Q (2019) Molecular characterization of caspase-8-like and its expression induced by microcystin-LR in grass carp (Ctenopharygodon idella). Fish Shellfish Immunol 89:727–735

    Article  CAS  PubMed  Google Scholar 

  • Weng D, Lu Y, Wei Y, Liu Y, Shen P (2007) The role of ROS in microcystin-LR-induced hepatocyte apoptosis and liver injury in mice. Toxicology 232:15–23

    Article  CAS  PubMed  Google Scholar 

  • Xiao H, Wu Y, Ting Z, Wang S, Sun G (2017) Effects of microcystin-LR on apoptosis, and caspase-3 and caspase-9 expression in human normal esophageal epithelial cells. Carcinogen Teratogen Mutagen 6:418–421

    Google Scholar 

  • Yang ZY, Zhang YL, Kun HU, Liu LS, Cai HG, Zhang FX, Yang XL (2018) Etiological and histopathological study on hepatopancreatic necrosis syndrome in Eriocheir sinensis. Acta Hydrobiol Sin 42:17–25

    Google Scholar 

  • Yuan J, Wang X, Gu Z, Zhang Y, Wang Z (2015) Activity and transcriptional responses of hepatopancreatic biotransformation and antioxidant enzymes in the oriental river prawn Macrobrachium nipponense exposed to microcystin-LR. Toxins 7:4006–4022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yuan J, Gu Z, Zheng Y, Zhang Y, Gao J, Chen S, Wang Z (2016) Accumulation and detoxification dynamics of microcystin-LR and antioxidant responses in male red swamp crayfish Procambarus clarkii. Aquat Toxicol 177:8–18

    Article  CAS  PubMed  Google Scholar 

  • Zhang D, Xie P, Chen J, Dai M, Qiu T (2009) Determination of microcystin-LR and its metabolites in snail (Bellamya aeruginosa), shrimp (Macrobrachium nipponensis) and silver carp (Hypophthalmichthys molitrix) from Lake Taihu, China. Chemosphere 76:974–981

    Article  CAS  PubMed  Google Scholar 

  • Zhang H, Cai C, Fang W, Wang J, Zhang Y, Liu J, Jia X (2013a) Oxidative damage and apoptosis induced by microcystin-LR in the liver of Rana nigromaculata in vivo. Aquat Toxicol 140:11–18

    Article  PubMed  Google Scholar 

  • Zhang YQ, Xiao CX, Lin BY, Shi Y, Liu YP, Liu JJ, Guleng B, Ren JL (2013b) Silencing of pokemon enhances caspase-dependent apoptosis via fas-and mitochondria-mediated pathways in hepatocellular carcinoma cells. PLoS One 8: e68981.

  • Zhang Y, Shi Q, Wei W, Xu F, Nie F (2019) Effects of microcystin-LR on the immune dysfunction and ultrastructure of hepatopancreas in giant freshwater prawn Macrobrachium rosenbergii. Fish Shellfish Immunol 89:586–594

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y, Zhuang H, Yang H, Xue W, Wang L (2019) Microcystin-LR disturbs testicular development of giant freshwater prawn Macrobrachium rosenbergii. Chemosphere 222:584–592

    Article  CAS  PubMed  Google Scholar 

  • Zhao ZQ, Velez DA, Wang NP, Hewan-Lowe KO, Vinten-Johansen J (2001) Progressively developed myocardial apoptotic cell death during late phase of reperfusion. Apoptosis 6:279–290

    Article  CAS  PubMed  Google Scholar 

  • Zhao Z, Yang P, Eckert RL, Reece EA (2009) Caspase-8: a key role in the pathogenesis of diabetic embryopathy. Birth Defects Res Part B Dev Reprod Toxicol 86:72–77

    Article  CAS  Google Scholar 

  • Zhou M, Tu WW, Xu J (2015) Mechanisms of microcystin-LR-induced cytoskeletal disruption in animal cells. Toxicon 101:92–100

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Natural Science Foundation of China [Grant Number 31802347]; the Fundamental Research Funds for the Central Universities [Grant Number KJQN201937]; the earmarked fund for Jiangsu Agricultural Industry Technology System [Grant Number JATS[2020]423], the Aquatic Three New Projects of Jiangsu Province [Grant Number D2018-4], and the Jiangsu Agriculture Science and Technology Innovation Fund (CX (19) 1006).

Author information

Authors and Affiliations

  1. Key Laboratory of Aquatic Nutrition and Feed Science of Jiangsu Province, National Experimental Teaching Center for Animal Science, College of Animal Science and Technology, Nanjing Agricultural University, No. 1 Weigang Road, Nanjing, 210095, Jiangsu Province, People’s Republic of China

    Cheng Chi, Xia-Wei Yu, Cai-Yan Zhang, Jia-Dai Liu, Ming-Wen Ye, Ding-Dong Zhang & Wen-Bin Liu

Authors
  1. Cheng Chi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xia-Wei Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cai-Yan Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jia-Dai Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ming-Wen Ye
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ding-Dong Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Wen-Bin Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

CC: Data curation, writing-original draft preparation, visualization, methodology, funding acquisition. JD-L: investigation. GZ-J: validation. XW-Y: resources, investigation. XF-L: resources. DD-ZDZ: formal analysis. WB-L: supervision conceptualization, project administration.

Corresponding authors

Correspondence to Cheng Chi or Wen-Bin Liu.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chi, C., Yu, XW., Zhang, CY. et al. Acute exposure to microcystin-LR induces hepatopancreas toxicity in the Chinese mitten crab (Eriocheir sinensis). Arch Toxicol 95, 2551–2570 (2021). https://doi.org/10.1007/s00204-021-03061-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00204-021-03061-9

Keywords

Search

Navigation