Intracellular Metabolism of Uranium and the Effects of Bisphosphonates on Its Toxicity

D.R. TASAT; N.S. ORONA; BOZAL CAROLA; A.M.UBIOS; R.L . CABRINI

Cell Metabolism - Cell Homeostasis and Stress Response

Año: 2012; p. 115 - 148

Uranium is the heaviest naturally occurring element found in the Earth?s crust. It is an alphaemitter radioactive element that present both radiotoxicant and chemotoxicant properties. Uranium is present in environment as a result of natural deposits and releases by human applications (mill tailings, nuclear industry and military army). The release of uranium or its by-products into the environment (air, soil and water) presents a threat to human health and to the environment as a whole. Uranium can enter the body by ingestion, inhalation or dermal contact yet, the primary route of entry into the body is inhalation. Research on inhaled, ingested, percutaneous and subcutaneous industrial uranium compounds has shown that solubility influences the target organ, the toxic response, and the mode of uranium excretion. The overall clearance rate of uranium compounds from the lung reflects both mechanical and dissolution processes depending on the morphochemical characteristics of uranium particles. In this review we emphasize on one of the principal physical characteristics of uranium particles, its size. As is known, based on uranium chemical composition, three different kinds are defined: natural, enriched (EU) and depleted (DU) uranium. The radiological and chemical properties of natural uranium and DU are similar. In fact, natural uranium has the same chemotoxicity, but its radiotoxicity is 60% higher. DU, being a waste product of uranium enrichment, has several civilian and military applications. Lately, it was used in international military conflicts (Gulf and recently as the Balkan Wars) and was claimed to contribute to health problems. Herein, we reviewed the toxicological data in vivo and in vitro on both natural and depleted uranium and renewed efforts to understand the intracellular metabolism of this heavy toxic metal. The reader will find this chapter divided in three sections. The first section, describes the presence of the uranium in the environment,the routes of entrance to the body and its impact on health. The second section which is committed to uranium cytotoxicity and its mechanism of action stressed on the oxidative metabolism and a third section dedicated to the effect of different compounds, mainly bisphosphonates, as substances with the ability to restrain uranium toxicity.