Institute of Biophysics SB RAS, Federal Research Center "Krasnoyarsk Science Center SB RAS, 660036 Krasnoyarsk, Russia.
Institute of Physics SB RAS, Federal Research Center "Krasnoyarsk Science Center SB RAS, 660036 Krasnoyarsk, Russia.
Int J Mol Sci. 2022 May 5;23(9):5152. doi: 10.3390/ijms23095152.
The Gd-containing metallofullerene derivatives are perspective magnetic resonance imaging contrast agents. We studied the bioeffects of a water-soluble fullerene derivative, gadolinium-endohedral fullerenol, with 40−42 oxygen groups (Gd@Fln). Bioluminescent cellular and enzymatic assays were applied to monitor toxicity and antioxidant activity of Gd@Fln in model solutions; bioluminescence was applied as a signaling physiological parameter. The Gd@Fln inhibited bioluminescence at high concentrations (>2·10−1 gL−1), revealing lower toxicity as compared to the previously studied fullerenols. Efficient activation of bioluminescence (up to almost 100%) and consumption of reactive oxygen species (ROS) in bacterial suspension were observed under low-concentration exposure to Gd@Fln (10−3−2·10−1 gL−1). Antioxidant capability of Gd@Fln was studied under conditions of model oxidative stress (i.e., solutions of model organic and inorganic oxidizers); antioxidant coefficients of Gd@Fln were determined at different concentrations and times of exposure. Contents of ROS were evaluated and correlations with toxicity/antioxidant coefficients were determined. The bioeffects of Gd@Fln were explained by hydrophobic interactions, electron affinity, and disturbing of ROS balance in the bioluminescence systems. The results contribute to understanding the molecular mechanism of “hormetic” cellular responses. Advantages of the bioluminescence assays to compare bioeffects of fullerenols based on their structural characteristics were demonstrated.
含钆金属富勒烯衍生物是有前景的磁共振成像对比剂。我们研究了一种水溶性富勒烯衍生物——具有 40-42 个氧基团的钆内包 fullerol（Gd@Fln）的生物效应。生物发光细胞和酶分析被应用于监测 Gd@Fln 在模型溶液中的毒性和抗氧化活性；生物发光被用作生理参数的信号。Gd@Fln 在高浓度（>2.10−1 gL−1）下抑制生物发光，显示出比以前研究的富勒醇更低的毒性。在低浓度（10−3-2.10−1 gL−1）暴露下，观察到 Gd@Fln 对细菌悬浮液中的生物发光有高效的激活作用（高达近 100%）和活性氧物质（ROS）的消耗。在模型氧化应激条件下（即模型有机和无机氧化剂溶液）研究了 Gd@Fln 的抗氧化能力；在不同浓度和暴露时间下测定了 Gd@Fln 的抗氧化系数。评估了 ROS 的含量，并确定了与毒性/抗氧化系数的相关性。用疏水性相互作用、电子亲和力和生物发光系统中 ROS 平衡的干扰来解释 Gd@Fln 的生物效应。该结果有助于理解“适应原性”细胞反应的分子机制。展示了生物发光分析在比较基于富勒醇结构特征的生物效应方面的优势。
