The involvement of oxidative and nitrosative stress mechanisms in several biological and pathological processes including aging, cancer, cardiovascular and neurodegenerative diseases has continued to fuel suggestions that processes can potentially be modulated by treatment with free-radical scavengers and antioxidant. The fermented papaya preparation (FPP) derived from Carica papaya Linn was investigated for its ability to modulate oxidative DNA damage due to H2O2 in rat pheochromocytoma (PC12) cells and protection of brain oxidative damage in hypertensive rats. Cells pre-treated with FPP (50 microg/ml) prior to incubation with H2O2 had significantly increased viability and sustenance of morphology and shape. The human hepatoma (HepG2) cells exposed to H2O2 (50 microM) showed an olive tail moment of 10.56 +/- 1.44 compared to 1.37 +/- 0.29 of the solvent control. A significant reduction (P < or = 0.05) of DNA damage was observed at concentrations > or = 10 microg/ml FPP, with 50 microg/ml FPP reducing the genotoxic effect of H2O2 by about 1.5-fold compared to only H2O2 exposed cells.