Journal of Applied Biosciences (J. Appl. Biosci.) [ISSN 1997 - 5902]
Volume 29: 1736 - 1742. Published May 10, 2010.
Effect of cyclophosphamide on transcription of SOD1mRNA and GPX1 mRNA in mice liver and brain tissues
*Hanaa AS Oraby, Amal AM Hassan, and Nadia AF Aboul Maaty
Cell Biology Department, National Research Center (NRC), El Behoth Street, Dokki, Cairo, Egypt
*Corresponding author: haoraby@gmail.comABSTRACT
Objectives: Limited information is available on the effect of chronic administration of cyclophoshamide (CP) on the transcription of genes coding for antioxidant enzymes. This work studied the effect of repeated doses of CP on transcription of genes coding for superoxide dismutases 1 (SOD1) and glutathione peroxidase 1 (GPX1) in mice liver and brain tissues.
Methodology and results: Three groups of mice were injected intraperitoneally with repeated doses of cyclophosphamide (4mg/kg) for 5, 10 or 15 consecutive days, respectively. Changes in transcription levels of SOD1 and GPX1 were assessed using reverse transcriptase polymerase chain reaction (RT- PCR) technology. Results indicated that transcription levels of GPX1 declined in liver tissue of treated animals whereas SOD1 transcription was slightly activated compared to the control. In brain cells, a dramatic depression in GPX1 transcription occurred after chronic administration of CP for five consecutive days. Exposure to CP for 10 or 15 days up-regulated the transcription of GPX1 mRNA significantly compared to the five days treatment group. Comparatively, significant decrease of transcription levels of SOD1 mRNA occurred at all CP exposure levels compared to the control.
Conclusion and application of findings: Chronic treatment of mice with cyclophosphamide affected the transcription levels of SOD1 mRNA and GPX1 mRNA in liver and brain tissues. These changes reflect the adverse effects of CP on the transcription levels of genes coding for two of the antioxidant enzymes defense system. The se results suggest that the liver is injured more by chronic treatment with CP and that an adaptive response develops in the brain cells by up regulating GPX1 gene transcription. These results further suggest there is need for precautions to be adopted among nurses, pharmacists, and workers who are occupationally exposed to cyclophosphamide during manufacturing, producing, distributing and dispensing of the drug.
Key words: Cyclophosphamide, oxidative stress, gene transcription, SOD1 and GPX1.
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