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MitoQ减轻辐射诱导的睾丸损伤:分子对接及毒性影响

MitoQ Mitigates Radiation-Induced Testicular Injury: Molecular Docking and Toxicity Implications.

作者信息

Ibrahim Ayman A, El-Gazzar Marwa G, Karam Heba M

机构信息

Drug Radiation Research Department, National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority (EAEA), Cairo, Egypt.

Department of Chemistry and Chemical Biology, McMaster University, Hamilton, ON, Canada.

出版信息

J Biochem Mol Toxicol. 2025 Aug;39(8):e70447. doi: 10.1002/jbt.70447.

DOI:10.1002/jbt.70447
PMID:40798902
Abstract

This study assessed the possible mitigating effect of a mitochondrion-targeted antioxidant (MitoQ) against gamma irradiation-induced testicular damage. The rats were distributed into five groups. The first group served as a control, the second group received MitoQ (2 mg/kg/day; i.p.) for 7 days, the third group was exposed to gamma radiation (5 gray as a single dose), the fourth group received MitoQ prophylactically before irradiation, and the last group was exposed to gamma radiation and then treated with MitoQ. The rats were killed 7 days after irradiation. MitoQ replenished mitochondrial ROS, indicating its antioxidant effect. MitoQ inhibited the intrinsic apoptosis cascade via a reduction in Bax and alleviated Bcl-2. MitoQ improved steroidogenesis, as verified by an increase in testosterone and upregulation of 3β-HSD and 17β-HSD expression, in addition to increasing complex I and succinate dehydrogenase activity. Likewise, sperm evaluation corroborated these findings. The acute toxicity profile of MitoQ was investigated in mice and was found to be 75 mg/kg body weight. Additionally, a molecular docking study of MitoQ showed a good fit to the active site of succinate dehydrogenase. In conclusion, this study introduces MitoQ as a new approach for the management of testicular damage triggered by gamma irradiation.

摘要

本研究评估了线粒体靶向抗氧化剂(MitoQ)对γ射线诱导的睾丸损伤的可能缓解作用。将大鼠分为五组。第一组作为对照组,第二组连续7天腹腔注射MitoQ(2毫克/千克/天),第三组接受单次剂量5格雷的γ射线照射,第四组在照射前预防性给予MitoQ,最后一组先接受γ射线照射,然后用MitoQ治疗。照射7天后处死大鼠。MitoQ补充了线粒体活性氧,表明其具有抗氧化作用。MitoQ通过降低Bax并减轻Bcl-2来抑制内源性凋亡级联反应。MitoQ改善了类固醇生成,这通过睾酮增加以及3β-羟类固醇脱氢酶(3β-HSD)和17β-羟类固醇脱氢酶(17β-HSD)表达上调得到证实,此外还增加了复合体I和琥珀酸脱氢酶的活性。同样,精子评估也证实了这些发现。对小鼠进行了MitoQ的急性毒性研究,发现其半数致死量为75毫克/千克体重。此外,MitoQ的分子对接研究表明它与琥珀酸脱氢酶的活性位点具有良好的契合度。总之,本研究将MitoQ作为一种管理γ射线照射引发的睾丸损伤的新方法进行了介绍。

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J Biochem Mol Toxicol. 2025 Aug;39(8):e70447. doi: 10.1002/jbt.70447.
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