State Key Laboratory of Food Science and Resources, Nanchang University, 235 Nanjing East Road, Nanchang 330047, China.
Int J Mol Sci. 2023 Aug 30;24(17):13424. doi: 10.3390/ijms241713424.
Cyclophosphamide causes side effects in cancer patients, including hepatotoxicity. Probiotics have recently emerged as potential approaches for the administration of many diseases. This study aimed to evaluate the protective effects of P101 against cyclophosphamide-induced liver injury and elucidate the underlying mechanism. In this study, P101 or GG were pre-administered to mice with varying duration (1 week, 2 weeks, and 3 weeks) before being intraperitoneally injected with cyclophosphamide at a dose of 30 mg/kg/day for 7 days to induce liver injury. Results demonstrated that cyclophosphamide-induced liver injury was characterized by histopathological disorders, including irregular central venous shape and hepatic vascular rupture, as well as a severe inflammation response and oxidative stress. The administration of probiotics for 3 weeks exerted the most significant improvements in alleviating liver injury, oxidative stress, and inflammation when compared to the shorter intervention duration. Notably, P101 exhibited more pronounced effects than GG. Furthermore, P101 enhanced the antioxidant defense system by activating the Nrf2/ARE signaling pathway, ultimately alleviating hepatotoxicity and hepatocyte apoptosis. In conclusion, this study highlighted the potential of P101 to alleviate cyclophosphamide-induced hepatotoxicity.
环磷酰胺会导致癌症患者产生副作用,包括肝毒性。益生菌最近被认为是治疗许多疾病的潜在方法。本研究旨在评估 P101 对环磷酰胺诱导的肝损伤的保护作用,并阐明其潜在机制。在这项研究中,在给小鼠腹腔注射 30mg/kg/天的环磷酰胺诱导肝损伤之前,用 P101 或 GG 以不同的时间(1 周、2 周和 3 周)进行预处理。结果表明,环磷酰胺诱导的肝损伤的特征是组织病理学紊乱,包括不规则的中央静脉形状和肝血管破裂,以及严重的炎症反应和氧化应激。与较短的干预时间相比,益生菌干预 3 周对减轻肝损伤、氧化应激和炎症的效果最为显著。值得注意的是,P101 的效果比 GG 更明显。此外,P101 通过激活 Nrf2/ARE 信号通路增强抗氧化防御系统,最终减轻肝毒性和肝细胞凋亡。综上所述,本研究强调了 P101 缓解环磷酰胺诱导的肝毒性的潜力。