Abstract
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.