钒化合物在癌症及糖尿病治疗中显示出其潜在的可能而受到人们的关注,但是其毒性限制了其作为药物的进一步发展。已有研究表明钒通过影响线粒体功能诱导的氧化应激是钒化合物毒性的主要原因。本工作主要考察了两种钒化合物.偏钒酸钠和乙酰丙酮氧钒对线粒体活性氧产生和呼吸链复合体活性的影响。结果表明,钒化合物依其化学物种的不同而对活性氧和复合体活性以不同的方式产生影响。偏钒酸钠抑制线粒体复合体Ⅰ和Ⅱ的活性,同时在低浓度范围内促进活性氧的产生。而氧钒化合物则促进复合体Ⅱ活性,同时促进复合体Ⅰ相关途径的电子漏。本工作为研究钒化合物作为抗糖尿病药物毒性提供了新的结果。
Vanadium compounds show potential in diabetes and cancer treatment, although the toxicity remains a great concern. Previous studies have shown that vanadium-induced oxidative stress affecting mitochondrial function is intensively responsible for the toxicity. In this work, we investigated the effects of the vanadium compounds sodium metavanadate (NaVO3) and vanadyl acetylacetonate (VO(acac)2) on mitochondrial ROS generation and respiratory complex activities. The experimental results showed that vanadium compounds affected the ROS generation and complex activities in different patterns depending on the chemical species. NaVO3 inhibited mitochondrial complexes Ⅰ and Ⅱ activities and stimulated ROS generation at low concentration range; while VO(acac)2 promoted complex Ⅱ activity but resulted in electron leakage from the complex Ⅰ-involved pathway. The present results provide new evidence for understanding the toxicity of antidiabetic vanadium compounds.