title: Mitochondrial toxicity of depleted uranium: protection by Beta-glucan.
abstract: Considerable evidence suggests that mitochondrial dysfunction contributes to the toxicity of uranyl acetate (UA), a soluble salt of depleted uranium (DU). We examined the ability of the two antioxidants, beta-glucan and butylated hydroxyl toluene (BHT), to prevent UA-induced mitochondrial dysfunction using rat-isolated kidney mitochondria. Beta-glucan (150 nM) and BHT (20 nM) attenuated UA-induced mitochondrial reactive oxygen species (ROS) formation, lipid peroxidation and glutathione oxidation. Beta-glucan and BHT also prevented the loss of mitochondrial membrane potential (MMP) and mitochondrial swelling following the UA treatment in isolated mitochondria. Our results show that beta-glucan and BHT prevented UA-induced mitochondrial outer membrane damage as well as release of cytochrome c from mitochondria. UA also decreased the ATP production in isolated mitochondria significantly inhibited with beta-glucan and BHT pre-treatment. Our results showed that beta-glucan may be mitochondria-targeted antioxidant and suggested this compound as a possible drug candidate for prophylaxis and treatment against DU-induced nephrotoxicity.
authors.affiliation: Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran. ; Faculty of Pharmacy, Manzandaran University of Medical Sciences, Sari, Iran. ; Students Research Committee, School of Pharmacy Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Shaki
authors.forename: Jalal
authors.initials: J
authors.lastname: Pourahmad
keywords: Antioxidant; Beta-glucan; Depleted uranium; Mitochondria; Nephrotoxicity; Protection