Organoselenium Compounds: A New Generation of Radioprotectors

Exposure of living organisms to ionizing radiation can cause health hazards and radioprotectors are employed to minimize such unwanted effects. Over the years a number of sulfhydryl compounds have been examined for radioprotection and only one agent, amifostine, is approved in the clinic. Selenium, a higher analogue of sulfur, is a micronutrient and a constituent of redox enzymes like glutathione peroxidase (GPx). With an aim to develop less toxic, GPx active, organoselenium compounds, as potential radioprotectors, we initiated a programme on synthesis and radioprotection studies of organoselenium compounds. In this article, the current status of research on selenium compounds as radioprotectors is presented. Radiation exposure and Radioprotectors Ionizing radiation, both high-energy electromagnetic and charged particles, has a wide spread usage in medicine, agriculture, energy, food storage, etc. and poses health hazards when used improperly. Exposure of living organisms to radiation can induce a number of abnormalities like mutation, cancer, and even death. When radiation interacts with living cells, water being the major constituent (~70%), undergoes radiolysis producing highly reactive free radical species, inducing oxidative stress. Cellular damage initiated by these radical species is the origin of tissue and organ injury . Depending on the type, exposure and linear energy transfer of the radiation, all these events occur within hours to weeks. Sometimes delayed and chronic effects are observable even after many months of exposure. The extent of radiation injury depends on the absorbed dose, expressed in the units of Gray (Gy), equal to one joule of energy deposition in one kilogram (1 J/kg) of the material. In addition to this, sensitivity of different organs equally determines the manifestation of radiation injury. For example, organs like brain, bone, muscle, thyroid, pituitary, adrenal and liver are radio-resistant, whereas others like lymphoid organs, reproductive organs, bone marrow and intestinal crypts are radiosensitive. Cellular oxygen enhances the radiation damage and reduced oxygen levels, as observed in certain hypoxic tumors, make them radioresistant. A radioprotector is a chemical substance or a mixture of compounds, capable of minimizing the damaging effects of ionizing radiation to normal tissue. Development of radioprotectors has been an area of active research from the beginning of the nuclear era. With the recognition that normal tissue protection during radiotherapy is as important as the destruction of the cancer cells, the focus of radioprotection research became more therapy oriented. However, an ideal radioprotector should be able to protect against the deleterious effect of any type of radiation during therapeutic procedures as well as during nuclear accidents. Additionally, a radioprotector should be inexpensive, have no toxic implications, and can be orally administered, with