Volume 78, Issue 4
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645


Praziquantel causes adverse effects after short-term treatment. To examine the mechanism of these effects, we studied the distribution of antigens and the expression of inducible nitric oxide synthase (iNOS), nuclear factor-κB (NF-κB), and antioxidant enzymes in -infected hamsters during short-term praziquantel treatment. Praziquantel-induced dispersion of parasite antigens produced a recruitment of inflammatory cells. NF-κB and iNOS mRNA expression was significantly elevated and associated with their immunoreactivity in the bile duct epithelium and inflammatory cells. Plasma nitrate, end products of nitric oxide, and malondialdehyde level increased significantly. Expression of mRNA for antioxidant enzymes (superoxide dismutases, catalase, and glutathione peroxidase) also increased significantly, which suggests host defense against oxidative stress. These results suggest that short-term praziquantel treatment induces inflammation and resulting oxidative and nitrative stress through antigen release. Data in this study can be used as a basis to understand potential side effects of praziquantel treatment in humans.


Article metrics loading...

Loading full text...

Full text loading...



  1. IARC, 1994. Infection with liver flukes (Opisthorchis viverrini, Opisthorchis felineus and Clonorchis sinensis). IARC Monogr Eval Carcinog Risks Hum 61 : 121–175.
  2. Jongsuksuntigul P, Imsomboon T, 2003. Opisthorchiasis control in Thailand. Acta Trop 88 : 229–232.
  3. Ohshima H, Bartsch H, 1994. Chronic infections and inflammatory processes as cancer risk factors: possible role of nitric oxide in carcinogenesis. Mutat Res 305 : 253–264.
  4. Coussens LM, Werb Z, 2002. Inflammation and cancer. Nature 420 : 860–867.
  5. Ohshima H, Tatemichi M, Sawa T, 2003. Chemical basis of inflammation-induced carcinogenesis. Arch Biochem Biophys 417 : 3–11.
  6. Pinlaor S, Hiraku Y, Ma N, Yongvanit P, Semba R, Oikawa S, Murata M, Sripa B, Sithithaworn P, Kawanishi S, 2004. Mechanism of NO-mediated oxidative and nitrative DNA damage in hamsters infected with Opisthorchis viverrini: a model of inflammation-mediated carcinogenesis. Nitric Oxide 11 : 175–183.
  7. Pinlaor S, Ma N, Hiraku Y, Yongvanit P, Semba R, Oikawa S, Murata M, Sripa B, Sithithaworn P, Kawanishi S, 2004. Repeated infection with Opisthorchis viverrini induces accumulation of 8-nitroguanine and 8-oxo-7,8-dihydro-2′-deoxy-guanine in the bile duct of hamsters via inducible nitric oxide synthase. Carcinogenesis 25 : 1535–1542.
  8. Pinlaor S, Hiraku Y, Yongvanit P, Tada-Oikawa S, Ma N, Pinlaor P, Sithithaworn P, Sripa B, Murata M, Oikawa S, Kawanishi S, 2006. iNOS-dependent DNA damage via NF-κB expression in hamsters infected with Opisthorchis viverrini and its suppression by the antihelminthic drug praziquantel. Int J Cancer 119 : 1067–1072.
  9. Bunnag D, Pungpark S, Harinasuta T, Viravan C, Vanijanonta S, Suntharasamai P, Migasena S, Charoenlarp P, Riganti M, LooAreesuwan S, 1984. Opisthorchis viverrini: clinical experience with praziquantel in Hospital for Tropical Diseases. Arzneimittelforschung 34 : 1173–1174.
  10. Matsumoto J, Matsuda H, 2002. Mast-cell-dependent histamine release after praziquantel treatment of Schistosoma japonicum infection: implications for chemotherapy-related adverse effects. Parasitol Res 88 : 888–893.
  11. Abend Y, Ashkenazy Y, Witzling V, Feigl D, Geltner D, Moshonov S, Zor U, 1996. Nitric oxide: a mediator in anaphylactic shock in guinea-pigs. J Basic Clin Physiol Pharmacol 7 : 57–69.
  12. Mak JC, Leung HC, Ho SP, Law BK, Lam WK, Tsang KW, Ip MS, Chan-Yeung M, 2004. Systemic oxidative and antioxidative status in Chinese patients with asthma. J Allergy Clin Immunol 114 : 260–264.
  13. Ceylan E, Aksoy N, Gencer M, Vural H, Keles H, Selek S, 2005. Evaluation of oxidative-antioxidative status and the L-arginine-nitric oxide pathway in asthmatic patients. Respir Med 99 : 871–876.
  14. Mitsuhata H, Shimizu R, Yokoyama MM, 1995. Role of nitric oxide in anaphylactic shock. J Clin Immunol 15 : 277–283.
  15. Kowluru RA, Kowluru V, Xiong Y, Ho YS, 2006. Overexpression of mitochondrial superoxide dismutase in mice protects the retina from diabetes-induced oxidative stress. Free Radic Biol Med 41 : 1191–1196.
  16. Sripa B, Kaewkes S, 2000. Localisation of parasite antigens and inflammatory responses in experimental opisthorchiasis. Int J Parasitol 30 : 735–740.
  17. Pinlaor S, Sripa B, Sithithaworn P, Yongvanit P, 2004. Hepatobiliary changes, antibody response, and alteration of liver enzymes in hamsters re-infected with Opisthorchis viverrini. Exp Parasitol 108 : 32–39.
  18. Gerard CJ, Olsson K, Ramanathan R, Reading C, Hanania EG, 1998. Improved quantitation of minimal residual disease in multiple myeloma using real-time polymerase chain reaction and plasmid-DNA complementarity determining region III standards. Cancer Res 58 : 3957–3964.
  19. Miranda KM, Espey MG, Wink DA, 2001. A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide 5 : 62–71.
  20. Nowak D, Kalucka S, Bialasiewicz P, Krol M, 2001. Exhalation of H2O2 and thiobarbituric acid reactive substances (TBARs) by healthy subjects. Free Radic Biol Med 30 : 178–186.
  21. Benzie IF, Strain JJ, 1996. The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: the FRAP assay. Anal Biochem 239 : 70–76.
  22. Liu LX, Weller PF, 1996. Antiparasitic drugs. N Engl J Med 334 : 1178–1184.
  23. Brindley PJ, Sher A, 1990. Immunological involvement in the efficacy of praziquantel. Exp Parasitol 71 : 245–248.
  24. Dean Befus YS, Moon TC, Munoz S, Befus AD, 2005. Role of nitric oxide in mast cells: controversies, current knowledge, and future applications. Immunol Res 33 : 223–239.
  25. Shorter D, Makone I, Elliott EJ, 2006. Fever and urticaria in an African refugee. J Paediatr Child Health 42 : 731–733.
  26. Matsumoto J, 2002. Adverse effects of praziquantel treatment of Schistosoma japonicum infection: involvement of host anaphylactic reactions induced by parasite antigen release. Int J Parasitol 32 : 461–471.
  27. Mendes AF, Caramona MM, Carvalho AP, Lopes MC, 2003. Differential roles of hydrogen peroxide and superoxide in mediating IL-1-induced NF-κB activation and iNOS expression in bovine articular chondrocytes. J Cell Biochem 88 : 783–793.
  28. Surh YJ, Chun KS, Cha HH, Han SS, Keum YS, Park KK, Lee SS, 2001. Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals: down-regulation of COX-2 and iNOS through suppression of NF-κB activation. Mutat Res 480–481 : 243–268.
  29. Balkwill F, Coussens LM, 2004. Cancer: an inflammatory link. Nature 431 : 405–406.
  30. Pinlaor S, Tada-Oikawa S, Hiraku Y, Pinlaor P, Ma N, Sithithaworn P, Kawanishi S, 2005. Opisthorchis viverrini antigen induces the expression of Toll-like receptor 2 in macrophage RAW cell line. Int J Parasitol 35 : 591–596.
  31. Miyake H, Sakal I, Harada K, Eto H, Hara I, 2004. Clinicopathological outcome of radical retropubic prostatectomy for 200 men with prostate cancer in a single institution in Japan. Hinyokika Kiyo 50 : 151–156.
  32. McCormick ML, Roeder TL, Railsback MA, Britigan BE, 1994. Eosinophil peroxidase-dependent hydroxyl radical generation by human eosinophils. J Biol Chem 269 : 27914–27919.
  33. Meilhac O, Zhou M, Santanam N, Parthasarathy S, 2000. Lipid peroxides induce expression of catalase in cultured vascular cells. J Lipid Res 41 : 1205–1213.
  34. Ikediobi CO, Badisa VL, Ayuk-Takem LT, Latinwo LM, West J, 2004. Response of antioxidant enzymes and redox metabolites to cadmium-induced oxidative stress in CRL-1439 normal rat liver cells. Int J Mol Med 14 : 87–92.
  35. Murley JS, Kataoka Y, Hallahan DE, Roberts JC, Grdina DJ, 2001. Activation of NFκB and MnSOD gene expression by free radical scavengers in human microvascular endothelial cells. Free Radic Biol Med 30 : 1426–1439.
  36. Kolodziejczyk L, Siemieniuk E, Skrzydlewska E, 2005. Antioxidant potential of rat liver in experimental infection with Fasciola hepatica. Parasitol Res 96 : 367–372.

Data & Media loading...

  • Received : 02 Dec 2007
  • Accepted : 08 Jan 2008

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error