735-744Ionizing radiation causes damage to biomolecules in living cells through oxidative stress by excessive generation of reactive oxygen species (ROS) from radiolysis of body water. Blood and its components including the cells are exposed to a significant dose of radiation during irradiation. Grapes (Vitis vinifera L.) contain several bioactive phytochemicals and are rich source of antioxidants. Therefore, we hypothesized that the grape extracts would offer protection against the ionizing radiation-induced damage of the red blood cells (RBCs). To test our hypothesis, in the current study we investigated the radio-protective actions of extract of four different grape (Vitis vinifera) cultivars, namely Flame seedless (Black grapes), Kishmish chorni (Black with reddish brown), Red globe (Red) and Thompson seedless mutant (Sonaka, Green) against the g-irradiation-induced oxidative stress leading to the structural alteration in the RBC membrane in vitro. Freshly drawn blood samples from healthy volunteers itself or mixed with grape extracts from seed, skin or pulp of each cultivar were irradiated at 4 Gy after one hour of treatment. -irradiation for one hour did not change the hematological parameters. The average osmotic fragility (H50) and the maximum rate of hemolysis (dH/dC)max increased after the -irradiation. The confocal microscopic and atomic force microscopic (AFM) studies showed that irradiation induced transformation of RBC from biconcave cells to echinocytes, altered their surface roughness and the vertical distance. The grape extracts did not alter the viability of human erythrocytes. Our results suggested that the grape extract pretreatment ameliorated the ionizing radiation-induced alterations at a dose of 4 Gy in human erythrocytes in vitro. Moreover, protection offered by the seed extract was significantly better than that that of skin or pulp of the same cultivar. Furthermore, the protective action of grape extract depends on its source (seed, skin or pulp) as well on cultivars