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Doxorubicin a photosensitive antibiotic is frequently used to treat various malignancies in clinics; however, doxorubicin is also taken up by the normal cells of the body leading to increased oxidative stress and subsequently DNA damage and dysfunction in the cells. The agents which can reduce the adverse effect of doxorubicin will of great value. The present study has attempted to study the effect of naringin a citrus flavonoid on the doxorubicininduced oxidative stress in mice liver. The mice were administered with 0, 1, 5 or 10mg/ kg body weight of doxorubicin and treated with 10mg/kg body weight of naringin before or after doxorubicin treatment. The glutathione concentration and lipid peroxidation and activities of glutathione-s-transferase, catalase and super oxide dismutase were studied at 0.5, 1, 2 and 4h post-treatment in the mouse liver. The doxorubicin increased the lipid peroxidation in a dose dependent manner at all the post treatment times. Conversely, it attenuated the activities of glutathione-s-transferase, catalase and super oxide dismutase in dose dependent fashion and time dependent manner. A similar effect was observed for glutathione concentration. Treatment of mice with naringin before or after doxorubicin treatment elevated all the antioxidants and reduced the doxorubicin -induced lipid peroxidation. The effect of naringin pretreatment was more effective when compared to its post treatment. The naringin was very effective in reducing the oxidative stress induced by doxorubicin as indicated by the elevated levels of glutathione concentration, glutathiones-transferase, catalase and super oxide dismutase. The pretreatment of naringin was better than its post treatment.

Molecular damage of DNA plays an important role in the cell killing and several anti-neoplastic agents exert their cytotoxic effects by inducing DNA damage in the cancer cells. DNA damaging effect of various concentrations of berberine chloride (BCL), an isoquinoline alkaloid was studied in HeLa cells by alkaline comet assay. The DNA damage has been expressed as olive tail moment (OTM). Incubation of HeLa cells with BCL for 4 h showed greater amount of DNA damage (OTM) than 2 h treatment. BCL treatment caused a concentration dependent rise in the DNA damage in HeLa cells and exposure of HeLa cells with 1 µg/ml BCL caused a10 fold rise in baseline DNA damage, whereasa maximum rise in DNA damage was observed in HeLa cells exposed to 8 µg/ml BCL. The study of DNA repair kinetics at different BCL post-treatment times revealed a constant rise in the DNA damage in BCL treated cells up to 24 h except for 1 -4 µg/ml BCL, where the highest DNA damage was observed at 12 h post-BCL treatment. The clonogenic assay showed that BCL treatment resulted in a concentration dependent rise in its cell killing effect. The cell survival and molecular DNA damage in HeLa cells treated with BCL has an inverse correlation indicating that with increased DNA damage cell survival declined. Our study demonstrates that anti-neoplastic effect of BCL is mainly due to its ability to cause damage to the cellular genome.

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