Uribe Pamela, Barra Javiera, Painen Kevin, Zambrano Fabiola, Schulz Mabel, Moya Claudia, Isachenko Vladimir, Isachenko Evgenia, Mallmann Peter, Sánchez Raúl
Center of Excellence in Translational Medicine-Scientific and Technological Bioresource Nucleus (CEMT-BIOREN), Faculty of Medicine, Universidad de La Frontera, Temuco 4810296, Chile.
Department of Internal Medicine, Faculty of Medicine, Universidad de La Frontera, Temuco 4781176, Chile.
Antioxidants (Basel). 2023 Jun 14;12(6):1272. doi: 10.3390/antiox12061272.
Excessive levels of reactive nitrogen species (RNS), such as peroxynitrite, promote nitrosative stress, which is an important cause of impaired sperm function. The metalloporphyrin FeTPPS is highly effective in catalyzing the decomposition of peroxynitrite, reducing its toxic effects in vivo and in vitro. FeTPPS has significant therapeutic potential in peroxynitrite-related diseases; however, its effects on human spermatozoa under nitrosative stress have not been described. This work aimed to evaluate the in vitro effect of FeTPPS against peroxynitrite-mediated nitrosative stress in human spermatozoa. For this purpose, spermatozoa from normozoospermic donors were exposed to 3-morpholinosydnonimine, a molecule that generates peroxynitrite. First, the FeTPPS-mediated peroxynitrite decomposition catalysis was analyzed. Then, its individual effect on sperm quality parameters was evaluated. Finally, the effect of FeTPPS on ATP levels, motility, mitochondrial membrane potential, thiol oxidation, viability, and DNA fragmentation was analyzed in spermatozoa under nitrosative stress conditions. The results showed that FeTPPS effectively catalyzes the decomposition of peroxynitrite without affecting sperm viability at concentrations up to 50 μmol/L. Furthermore, FeTPPS mitigates the deleterious effects of nitrosative stress on all sperm parameters analyzed. These results highlight the therapeutic potential of FeTPPS in reducing the negative impact of nitrosative stress in semen samples with high RNS levels.
过量的活性氮物质（RNS），如过氧亚硝酸盐，会加剧亚硝化应激，这是精子功能受损的一个重要原因。金属卟啉FeTPPS在催化过氧亚硝酸盐分解方面非常有效，可在体内和体外降低其毒性作用。FeTPPS在与过氧亚硝酸盐相关的疾病中具有显著的治疗潜力；然而，尚未有人描述过其在亚硝化应激下对人类精子的影响。这项研究旨在评估FeTPPS对过氧亚硝酸盐介导的人类精子亚硝化应激的体外作用。为此，将正常精子捐献者的精子暴露于能产生过氧亚硝酸盐的分子3-吗啉代-sydnonimine中。首先，分析了FeTPPS介导的过氧亚硝酸盐分解催化作用。然后，评估了其对精子质量参数的单独影响。最后，分析了FeTPPS在亚硝化应激条件下对精子的ATP水平、活力、线粒体膜电位、硫醇氧化、活力和DNA片段化的影响。结果表明，在浓度高达50μmol/L时，FeTPPS能有效催化过氧亚硝酸盐的分解，且不影响精子活力。此外，FeTPPS减轻了亚硝化应激对所有分析的精子参数的有害影响。这些结果凸显了FeTPPS在降低高RNS水平精液样本中亚硝化应激负面影响方面的治疗潜力。
