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Oxidative and Nitrative Stress in Opisthorchis viverrini–Infected Hamsters: An Indirect Effect after Praziquantel Treatment

Praziquantel causes adverse effects after short-term treatment. To examine the mechanism of these effects, we studied the distribution of Opisthorchis viverrini antigens and the expression of inducible nitric oxide synthase (iNOS), nuclear factor-B (NF-B), and antioxidant enzymes in O. viverrini-infected hamsters during short-term praziquantel treatment. Praziquantel-induced dispersion of parasite antigens produced a recruitment of inflammatory cells. NF-B 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 O. viverrini antigen release. Data in this study can be used as a basis to understand potential side effects of praziquantel treatment in humans.

Received December 2, 2007. Accepted for publication January 8, 2008.

Acknowledgments: We thank Thaweesak Saraboon for technical support and R. H. Andrews for comments on the manuscript while supported by the Faculty of Medicine Khon Kaen University Overseas Visiting Professor Program.

Financial support: This work was supported by the Khon Kaen University Research Fund (grant no. 48-49-03-1-01-01), the Thailand Research Fund (grant no. MRG4880128) in Thailand, and Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan.

^* Address correspondence to Somchai Pinlaor, Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. E-mail: psomec{at}kku.ac.th

Authors’ addresses: Somchai Pinlaor, Suksanti Prakobwong, Butsara Kaewsamut, Thidarut Boonmars, and Paiboon Sithithaworn, Department of Parasitology, and Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand, Telephone: 66-43-348-387, Fax: 66-43-202-475. Yusuke Hiraku, Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie, 514-8507, Japan. Somkid Dechakhamphu and Puangrat Yongvanit, Department of Biochemistry, and Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand, Telephone: 66-43-348-386. Porntip Pinlaor, Department of Clinical Microbiology, Faculty of Associated Medical Science, and Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand. Ning Ma, Department of Anatomy and Developmental Neurobiology Institute of Health Biosciences, The University of Tokushima Graduate School 3-18-15 Kuramoto-cho Tokushima 770-8503, Japan. Shosuke Kawanishi, Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie, 514-8507, and Faculty of Health Science, Suzuka University of Medical Science, 1001-1 Kishioka, Suzuka, Mie 510-0293, Japan.