Abstract
Objective
The protection conferred by a series of synthetic organoselenium compounds against genotoxicity and oxidative stress induced by a reference mutagen cyclophosphamide (CP) was assessed.
Method
Genotoxicity was induced in mice by CP treatment (25 mg/kg b.w.) for 10 consecutive days. Organoselenium compounds (3 mg/kg b.w.) were administered orally in a concomitant and pretreatment schedule. DNA damage in peripheral blood lymphocytes and frequency of chromosomal aberration in the bone marrow cells were measured. Liver tissues were collected for analysis of the activity of antioxidant and detoxifying enzymes, lipid peroxidation (LPO) level, glutathione content, and histopathology.
Results
Exposure to CP not only led to a significant increase in the percent of chromosomal aberration and DNA damage, but also enhanced generation of hepatic reactive oxygen species (ROS) and LPO level. The organoselenium compounds demonstrated marked functional protection against CP-induced genotoxicity. DNA damage and chromosomal aberration along with ROS generation were attenuated in the organoselenium-treated mice compared with the CP-treated control mice. CP caused marked depression in the activities of the selenoenzymes (glutathione peroxidase (GPx) and thioredoxin reductase (TRxR)) and other detoxifying and antioxidant enzymes, while treatment with organoselenium compounds restored all these activities towards normal.
Discussion
The protective effect of these compounds may be primarily associated with the improvement of the activity of antioxidant and detoxifying enzymes (including the selenoenzymes, GPx, and TRxR) that are known to protect the DNA and other cellular components from oxidative damage.
Acknowledgements
This work was supported by Grant from CSIR (01(2160)/07/EMR II). Somnath Singha Roy gratefully acknowledges CSIR for Junior Research Fellowship. The authors also thank Dr Syamsundar Mandal, Department of Epidemiology and Biostatistics, CNCI, Kolkata for his valuable suggestion regarding statistical analysis, Dr Ila Das, Department of Cancer Chemoprevention, CNCI, Kolkata, and Santu Sarkar, IISER, Kolkata for their support in doing this work.
Conflict of interest
The authors alone are responsible for the content and writing of the paper.