Faculty of Pharmacy, Shaheed Beheshti University of Medical Sciences, Tehran, Iran.
Hum Exp Toxicol. 2011 Mar;30(3):173-81. doi: 10.1177/0960327110372643. Epub 2010 Jun 3.
Previous reports suggested that certain carbohydrate polymers, such as β-(1→3)-D-glucan, may possess free radical scavenging activity. The present study examined the free radical scavenging activity of a carbohydrate polymer, β-(1→3)-D-glucan against oxidative stress induced by depleted uranium in isolated rat hepatocytes. Addition of U (VI) (uranyl acetate) to isolated rat hepatocytes results in reactive oxygen species (ROS) formation, rapid glutathione depletion, mitochondrial membrane potential collapse and lysosomal membrane rupture before hepatocyte lysis occurred. Our results showed that quite similar to silymarin, which is a known antioxidant and radical scavenger, tiny concentration of β-glucan (138 nM) very successfully protected the hepatocytes against cell lysis and all oxidative stress cytotoxicity endpoints caused by depleted uranium including ROS formation, glutathione depletion, decreased mitochondrial membrane potential, lysosomal membrane rupture and caspase 3 activity increase. In conclusion, our results confirmed the antioxidant and radical scavenging activity of β-(1→3)-D-glucan and suggested this compound and silymarin as possible drug candidates for prophylaxis and treatment against depleted uranium toxic effects.
先前的报告表明,某些碳水化合物聚合物,如β-(1→3)-D-葡聚糖,可能具有清除自由基的活性。本研究检测了一种碳水化合物聚合物β-(1→3)-D-葡聚糖对 depleted uranium 诱导的离体大鼠肝细胞氧化应激的自由基清除活性。向分离的大鼠肝细胞中添加 U(VI)(醋酸铀酰)会导致活性氧(ROS)形成、谷胱甘肽迅速耗竭、线粒体膜电位崩溃和溶酶体膜破裂,然后发生肝细胞裂解。我们的结果表明,与已知的抗氧化剂和自由基清除剂水飞蓟素非常相似,极少量的β-葡聚糖(138 nM)非常成功地保护了肝细胞免受细胞裂解和 depleted uranium 引起的所有氧化应激细胞毒性终点的影响,包括 ROS 形成、谷胱甘肽耗竭、线粒体膜电位降低、溶酶体膜破裂和 caspase 3 活性增加。总之,我们的结果证实了β-(1→3)-D-葡聚糖的抗氧化和清除自由基活性,并表明该化合物和水飞蓟素可能是预防和治疗 depleted uranium 毒性作用的候选药物。