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