Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdańsk, Gdańsk, Poland.
Department of Cell Biology and Immunology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Gdańsk, Poland.
Sci Rep. 2024 Oct 23;14(1):25056. doi: 10.1038/s41598-024-76143-0.
Cyclophosphamide (CPAm) is a widely used chemotherapeutic agent that exhibits potent anti-cancer properties but is often associated with debilitating side effects. Despite its efficacy, the management of CPAm-induced toxicities remains a significant clinical challenge. There has been growing interest in exploring complementary and alternative therapies to mitigate these adverse effects in recent years, and this may be a chance for the earthworm-derived preparation, Venetin-1. Its rich composition of bioactive compounds has demonstrated promising pharmacological properties, including anti-inflammatory, antioxidant, and immunomodulatory effects. These properties suggest its potential to counteract various systemic toxicities induced by CPAm. We conducted a comprehensive study to investigate the effect of Venetin-1 on cyclophosphamide-induced toxicity. Mice were administered CPAm for four days, followed by application of the earthworm preparation in two doses (50 mg/kg and 100 mg/kg b.w). Importantly, the preparation did not cause any side effects in all mice, ensuring the safety of the intervention. We then determined global changes in the proteome using proteomics and quantitative SWATH-MS analysis, which is a robust and reliable method. This allowed us to identify up- and downregulated proteins in each studied group, providing valuable insights into the mechanism of action of Venetin-1. As shown by the results, Venetin-1 had a significant effect on the proteome of mouse lung tissue. It was possible to determine quantitative changes in 400 proteins, and the analysis after administration of Venetin-1 showed a change in the global proteomic profile from upregulated to down-regulated. The stimulating properties of the preparation concerning the complement system were also confirmed in a separate validation experiment. Venetin-1 shows promise in reducing the harmful effects of cyclophosphamide on lung tissue. It encourages tissue regeneration, reduces inflammation, supports autophagy, and boosts the immune system. However, more research is needed to thoroughly elucidate and describe the benefits of Venetin-1.
环磷酰胺（CPAm）是一种广泛应用的化疗药物，具有强大的抗癌特性，但常伴有严重的副作用。尽管它具有疗效，但 CPAm 诱导的毒性的管理仍然是一个重大的临床挑战。近年来，人们越来越关注探索补充和替代疗法，以减轻这些不良反应，而这可能为蚯蚓衍生制剂 Venetin-1 提供了机会。它丰富的生物活性化合物组成表现出有希望的药理学特性，包括抗炎、抗氧化和免疫调节作用。这些特性表明它有可能对抗 CPAm 诱导的各种全身毒性。我们进行了一项全面的研究，以调查 Venetin-1 对环磷酰胺诱导的毒性的影响。小鼠连续四天给予 CPAm，然后用两种剂量（50mg/kg 和 100mg/kg b.w.）的蚯蚓制剂进行处理。重要的是，该制剂在所有小鼠中均未引起任何副作用，确保了干预的安全性。然后，我们使用蛋白质组学和定量 SWATH-MS 分析来确定蛋白质组的全局变化，这是一种强大可靠的方法。这使我们能够识别每个研究组中上调和下调的蛋白质，为 Venetin-1 的作用机制提供了有价值的见解。结果表明，Venetin-1 对小鼠肺组织的蛋白质组有显著影响。可以确定 400 种蛋白质的定量变化，并且 Venetin-1 给药后的分析显示，从上调到下调的全局蛋白质组谱发生了变化。在单独的验证实验中还证实了该制剂对补体系统的刺激特性。Venetin-1 有望减少环磷酰胺对肺组织的有害影响。它鼓励组织再生，减少炎症，支持自噬，并增强免疫系统。然而，需要进一步的研究来彻底阐明和描述 Venetin-1 的益处。
