Skip to main content
Log in

Cysticercus fasciolaris infection induced oxidative stress and apoptosis in rat liver: a strategy for host-parasite cross talk

  • Original Paper
  • Published:
Parasitology Research Aims and scope Submit manuscript

Abstract

Parasitic helminths have developed various strategies to induce or inhibit apoptosis in the cells of their host, thereby modulating the host’s immune response and aiding dissemination to the host. Cysticercus fasciolaris, the larval form of Taenia taeniaeformis, parasitized different intermediate hosts like rats, rabbits, etc. and is cosmopolitan in distribution. In the present study, we have investigated host-parasite interactions and the resulting effect of C. fasciolaris in the liver of rat. Histology of the infected livers showed dilation and damages of hepatic cells near the parasite. Infected liver cells showed an increase in DNA fragmentation and chromatin condensation compared to the normal liver. Acridine orange and ethidium bromide dual staining revealed the presence of apoptotic cells in the infected liver. The decline in the mitochondrial membrane potential in the infected liver suggested that the observed apoptosis is mitochondria mediated. Occurrence of an elevated level of active executioner caspases 3/7 in the infected rat liver further confirms the occurrence of apoptosis. Different antioxidant enzymes were also evaluated and revealed a notable decline in the level of glutathione and glutathione-S-transferase activity leading to the augmented generation of reactive oxygen species. Results of the present study revealed that C. fasciolaris infection leads to apoptosis in the liver of rats which may be a surviving strategy for the parasitic larvae.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

TUNEL:

Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling

DAPI:

4′,6-Diamidine-2-phenylindole dihydrochloride

AO:

Acridine orange

EB:

Ethidium bromide

JC-1:

5,5′,6,6-Tetrachloro-1,1,3,3′-tetraethylbenzimidazolylcarbocyanine iodide

FLICA:

Fluorescent-labeled inhibitor of caspases

GSH:

Glutathione

GST:

Glutathione-S-transferase

SOD:

Superoxide dismutase

ROS:

Reactive oxygen species

DMSO:

Dimethyl sulfoxide

OMM:

Outer mitochondrial membrane

MMP:

Mitochondria membrane potential

References

  • Bar-Peled O, Korkotian E, Segal M, Groner Y (1996) Constitutive overexpression of Cu/Zn superoxide dismutase exacerbates kainic acid-induced apoptosis of transgenic-Cu/Zn superoxide dismutase neurons. Proc Natl Acad Sci U S A 93:8530–8535

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bojes HK, Feng X, Kehrer JP, Cohen GM (1999) Apoptosis in hematopoietic cells (FL5.12) caused by interleukin-3 withdrawal: relationship to caspase activity and the loss of glutathione. Cell Death Differ 6(1):61–70

    Article  CAS  PubMed  Google Scholar 

  • Boots M, Hudson PJ, Sasaki A (2004) Large shifts in pathogen virulence relate to host population structure. Science 303:842–844

    Article  CAS  PubMed  Google Scholar 

  • Bush AO, Fernández JC, Esch GW, Seed JR (2001) Parasitism: the diversity and ecology of animal parasites. Cambridge University Press, Cambridge

    Google Scholar 

  • Choi HS, Kim JW, Cha YN, Kim C (2006) A quantitative nitroblue tetrazolium assay for determining intracellular superoxide anion production in phagocytic cells. J Immunoassay Immunochem 27:31–44

    Article  CAS  PubMed  Google Scholar 

  • Combes C (2001) Parasitism: the ecology and evolution of intimate interactions. University of Chicago Press, Chicago

    Google Scholar 

  • Cotgreave IA (2003) Analytical developments in the assay of intra‐and extracellular GSH homeostasis: specific protein S-glutathionylation, cellular GSH and mixed disulphide compartmentalisation and interstitial GSH redox balance. Biofactors 17(1–4):269–277

    Article  CAS  PubMed  Google Scholar 

  • Davis W, Ronai ZE, Tew KD (2001) Cellular thiols and reactive oxygen species in drug-induced apoptosis. J Pharmacol Exp Ther 296:1–6

    CAS  PubMed  Google Scholar 

  • Day T, Burns JG (2003) A consideration of patterns of virulence arising from host-parasite coevolution. Evolution Int J Org Evolution 57:671–676

    Article  Google Scholar 

  • Frand AR, Kaiser CA (2000) Two pairs of conserved cysteines are required for the oxidative activity of Ero1p in protein disulfide bond formation in the endoplasmic reticulum. Mol Biol Cell 11:2833–2843

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Frank SN, Faust S, Kalbe M, Trubiroha A, Kloas W, Sures B (2011) Fish hepatic glutathione-S-transferase activity is affected by the cestode parasites Schistocephalus solidus and Ligula intestinalis: evidence from field and laboratory studies. Parasitology 138(07):939–944

    Article  CAS  PubMed  Google Scholar 

  • Green DR, Reed JC (1998) Mitochondria and apoptosis. Science 281(5381):1309

    Article  CAS  PubMed  Google Scholar 

  • Gupta S, Bhatia V, Wen JJ, Wu Y, Huang MH, Garg NJ (2009) Trypanosoma cruzi infection disturbs mitochondrial membrane potential and ROS production rate in cardiomyocytes. Free Radical Biol Med 47(10):1414–1421

    Article  CAS  Google Scholar 

  • Habig WH, Pabst MJ, Jakoby WB (1974) Glutathione S-transferases: the first enzymatic step in mercapturic acid formation. J Biol Chem 249:7130–7139

    CAS  PubMed  Google Scholar 

  • Hengartner MO (2000) The biochemistry of apoptosis. Nature 407:770–776

    Article  CAS  PubMed  Google Scholar 

  • Irizarry-Rovira AR, Wolf A, Bolek M (2007) Taenia taeniaeformis-induced metastatic hepatic sarcoma in a pet rat (Rattus norvegicus). J Exot Pet Med 16(1):45–48

    Article  Google Scholar 

  • Kahl R, Kampkötter A, Wätjen W, Chovolou Y (2004) Antioxidant enzymes and apoptosis. Drug Metab Rev 36:747–762

    Article  CAS  PubMed  Google Scholar 

  • Kaur P, Shrivastav R, Qureshi TA (2013) Pathological effects of Eustrongylides sp. larvae (Dioctophymatidae) infection in freshwater fish, Glossogobius giuris (Ham.) with special reference to ovaries. J Parasit Dis 37(2):245–250

    Article  PubMed  Google Scholar 

  • Kerr JFR, Willie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26:239–257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kerr JFR, Searle J, Harmon BV, Bishop CJ (1987) Perspectives in mammalian cell death. In: Potten CS (ed) Apoptosis. Oxford University Press, Oxford, pp 93–128

    Google Scholar 

  • Koeppel M, Garcia-Alcalde F, Glowinski F, Schlaermann P, Meyer TF (2015) Helicobacter pylori infection causes characteristic DNA damage patterns in human cells. Cell Rep 11(11):1703–1713

    Article  CAS  PubMed  Google Scholar 

  • Kumar PR, Ravindran R, Lakshmanan B, Senthamil Selvan P, Subramanian H, Sreekumaran T (2007) Pathology of nodular tapeworm in backyard poultry. J Parasit Dis 31:54–55

    Google Scholar 

  • Liu X, Kim CN, Yang J, Jemmerson R, Wang X (1996) Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell 86:147–157

    Article  CAS  PubMed  Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

    CAS  PubMed  Google Scholar 

  • Mannervik B, Danielson UH (1988) Glutathione transferases—structure and catalytic activity. CRC Crit Rev Biochem 23:283–337

    Article  CAS  PubMed  Google Scholar 

  • McCord JM, Fridovich I (1969) Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). J Biol Chem 244:6049–6055

    CAS  PubMed  Google Scholar 

  • Modjtahedi N, Giordanetto F, Madeo F, Kroemer G (2006) Apoptosis-inducing factor: vital and lethal. Trends Cell Biol 16:264–272

    Article  CAS  PubMed  Google Scholar 

  • Montero R, Serrano L, Dávila VM, Ito A, Plancarte A (2003) Infection of rats with Taenia taeniformis metacestodes increases hepatic CYP450, induces the activity of CYP1A1, CYP2B1 and COH isoforms and increases the genotoxicity of the procarcinogens benzo[a]pyrene, cyclophosphamide and aflatoxin B1. Mutagenesis 18(2):211–216

    Article  CAS  PubMed  Google Scholar 

  • OuYang L, Wei J, Wu Z, Zeng X, Li Y, Jia Y, Ma Y, Zhan M, Lei W (2012) Differences of larval development and pathological changes in permissive and nonpermissive rodent hosts for Angiostrongylus cantonensis infection. Parasitol Res 111(4):1547–1557

    Article  PubMed  Google Scholar 

  • Pias EK, Ekshyyan OY, Rhoads CA, Fuseler J, Harrison L, Aw TY (2003) Differential effects of superoxide dismutase isoform expression on hydroperoxide-induced apoptosis in PC-12 cells. J Biol Chem 278:13294–13301

    Article  CAS  PubMed  Google Scholar 

  • Rausch RL (1994) Family: Taeniidae. In: Khalil LF, Jones A, Bray RA (eds) Keys to the cestode parasites of vertebrates. CAB International, Wallingford, pp 665–672

    Google Scholar 

  • Rodriguez J, Lazebnik Y (1999) Caspase-9 and APAF-1 form an active holoenzyme. Genes Dev 13:3179–3184

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shao Q, Tohma Y, Ohgaki H, Ohshima H (2003) Altered expression of Fas (APO-1, CD95) and Fas ligand in the liver of mice infected with Schistosoma japonicum and Schistosoma mansoni: implications for liver carcinogenesis. Asian Pac J Cancer Prevent 3:361–366

    Google Scholar 

  • Singh A, Rathaur S (2010) Combination of DEC plus aspirin induced mitochondrial mediated apoptosis in filarial parasite Setaria cervi. Biochimie 92:894–900

    Article  CAS  PubMed  Google Scholar 

  • Singla N, Singla LD, Gupta K, Sood NK (2013) Pathological alterations in natural cases of Capillaria hepatica infection alone and in concurrence with Cysticercus fasciolaris in Bandicita bengalensis. J Parasit Dis 37(1):16–20

    PubMed  Google Scholar 

  • Skálová L, Křížová V, Cvilink V, Szotáková B, Štorkánová L, Velík J, Lamka J (2007) Mouflon (Ovis musimon) dicrocoeliosis: effects of parasitosis on the activities of biotransformation enzymes and albendazole metabolism in liver. Vet Parasitol 146(3):254–262

    Article  PubMed  Google Scholar 

  • Swamy SM, Huat BT (2003) Intracellular glutathione depletion and reactive oxygen species generation are important in alpha-hederin-induced apoptosis of P388 cells. Mol Cell Biochem 245:127–139

    Article  PubMed  Google Scholar 

  • Woolhouse MEJ, Webster JP, Domingo E, Charlesworth B, Levin BR (2002) Biological and biomedical implications of the co-evolution of pathogens and their hosts. Nat Genet 32:569–577

    Article  CAS  PubMed  Google Scholar 

  • Wyllie AH, Morris RG, Smith AL, Dunlop D (1984) Chromatin cleavage in apoptosis: association with condensed chromatin morphology and dependence on macromolecular synthesis. J Pathol 142(1):67–77

    Article  CAS  PubMed  Google Scholar 

  • Yongvanit P, Pinlaor S, Bartsch H (2012) Oxidative and nitrative DNA damage: key events in opisthorchiasis-induced carcinogenesis. Parasitol Int 61(1):130–135

    Article  CAS  PubMed  Google Scholar 

  • Zhang DW, Shao J, Lin J, Zhang N, Lu BJ, Lin SC, Dong MQ, Han J (2009) RIP3, an energy metabolism regulator that switches TNF-induced cell death from apoptosis to necrosis. Science 325:332–336

    Article  CAS  PubMed  Google Scholar 

  • Zou H, Li Y, Liu X, Wang X (1999) An APAF-1⋅cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9. J Biol Chem 274:11549–11556

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors are thankful to UGC for financial support in the form of DSA program to the Department of Zoology, North-Eastern Hill University, Shillong. BRG is indebted to UGC for meritorious fellowship (UGC-BSR) in the form of JRF and SRF.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Bishnupada Roy.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Giri, B.R., Roy, B. Cysticercus fasciolaris infection induced oxidative stress and apoptosis in rat liver: a strategy for host-parasite cross talk. Parasitol Res 115, 2617–2624 (2016). https://doi.org/10.1007/s00436-016-5008-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00436-016-5008-3

Keywords

Navigation