Keppler Frank, Boros Mihály, Polag Daniela
Institute of Earth Sciences, Heidelberg University, D-69120 Heidelberg, Germany.
Heidelberg Center for the Environment (HCE), Heidelberg University, D-69120 Heidelberg, Germany.
Antioxidants (Basel). 2023 Jul 4;12(7):1381. doi: 10.3390/antiox12071381.
Methane (CH), which is produced endogenously in animals and plants, was recently suggested to play a role in cellular physiology, potentially influencing the signaling pathways and regulatory mechanisms involved in nitrosative and oxidative stress responses. In addition, it was proposed that the supplementation of CH to organisms may be beneficial for the treatment of several diseases, including ischemia, reperfusion injury, and inflammation. However, it is still unclear whether and how CH is produced in mammalian cells without the help of microorganisms, and how CH might be involved in physiological processes in humans. In this study, we produced the first evidence of the principle that CH is formed non-microbially in the human body by applying isotopically labeled methylated sulfur compounds, such as dimethyl sulfoxide (DMSO) and methionine, as carbon precursors to confirm cellular CH formation. A volunteer applied isotopically labeled (H and C) DMSO on the skin, orally, and to blood samples. The monitoring of stable isotope values of CH convincingly showed the conversion of the methyl groups, as isotopically labeled CH was formed during all experiments. Based on these results, we considered several hypotheses about endogenously formed CH in humans, including physiological aspects and stress responses involving reactive oxygen species (ROS). While further and broader validation studies are needed, the results may unambiguously serve as a proof of concept for the endogenous formation of CH in humans via a radical-driven process. Furthermore, these results might encourage follow-up studies to decipher the potential physiological role of CH and its bioactivity in humans in more detail. Of particular importance is the potential to monitor CH as an oxidative stress biomarker if the observed large variability of CH in breath air is an indicator of physiological stress responses and immune reactions. Finally, the potential role of DMSO as a radical scavenger to counteract oxidative stress caused by ROS might be considered in the health sciences. DMSO has already been investigated for many years, but its potential positive role in medical use remains highly uncertain.
甲烷（CH）由动植物内源性产生，最近有研究表明其在细胞生理中发挥作用，可能影响与亚硝化和氧化应激反应相关的信号通路及调节机制。此外，有人提出向生物体补充CH可能对治疗多种疾病有益，包括缺血、再灌注损伤和炎症。然而，目前仍不清楚在没有微生物帮助的情况下，哺乳动物细胞是否以及如何产生CH，以及CH如何参与人类的生理过程。在本研究中，我们通过应用同位素标记的甲基化硫化合物，如二甲基亚砜（DMSO）和蛋氨酸，作为碳前体来确认细胞CH的形成，从而首次证明了人体中CH可通过非微生物方式形成这一原理。一名志愿者在皮肤、口服以及血液样本中应用了同位素标记（氢和碳）的DMSO。对CH稳定同位素值的监测令人信服地表明了甲基的转化，因为在所有实验过程中均形成了同位素标记的CH。基于这些结果，我们考虑了关于人体内内源性形成CH的几种假设，包括生理方面以及涉及活性氧（ROS）的应激反应。虽然需要进一步更广泛的验证研究，但这些结果无疑可作为人体通过自由基驱动过程内源性形成CH的概念验证。此外，这些结果可能会鼓励后续研究更详细地解读CH在人体中的潜在生理作用及其生物活性。特别重要的是，如果观察到呼出气体中CH的巨大变异性是生理应激反应和免疫反应的指标，那么将CH作为氧化应激生物标志物进行监测的可能性。最后，在健康科学领域可能会考虑DMSO作为自由基清除剂来对抗ROS引起的氧化应激的潜在作用。DMSO已经研究多年，但其在医学应用中的潜在积极作用仍高度不确定。
