Mitochondrial Toxicity of Depleted Uranium: Protection by Beta-Glucan

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.