School of Pharmacy, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Minhang District, Shanghai 200240, China; State Key Laboratory of Microbial Metabolism, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Minhang District, Shanghai 200240, China.
School of Pharmacy, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Minhang District, Shanghai 200240, China.
Biomed Pharmacother. 2021 Nov;143:112192. doi: 10.1016/j.biopha.2021.112192. Epub 2021 Sep 25.
Irinotecan (CPT-11) is a camptothecin chemotherapy drug largely used in treating cancers. However, its strong adverse effects, such as gastrointestinal and hepatic toxicities, tend to reduce the patients' life qualities and to limit the clinical use of CPT-11. The protective roles of selenium (Se) and probiotics against CPT-11-induced toxicity have been widely reported. However, the application of Se-enriched probiotics in the adjuvant therapy of CPT-11 has not been well explored. The purpose of this study is to evaluate the in-vitro and in-vivo effects of Se-enriched Bifidobacterium longum DD98 (Se-B. longum DD98) as a chemotherapy preventive agent on alleviating intestinal and hepatic toxicities induced by CPT-11 chemotherapy. The results showed that Se-B. longum DD98 positively regulated the aberrant cell viability and oxidative stress induced by CPT-11 both in human normal liver (L-02) and rat small intestinal epithelial (IEC-6) cell lines. In vivo experiment revealed that Se-B. longum DD98 significantly attenuated intestinal and hepatic toxicities by ameliorating symptoms such as body weight loss and diarrhea, and by improving the biochemical indicators of hepatotoxicity and oxidative stress. Furthermore, we discovered that the protective effects of Se-B. longum DD98 based largely upon decreasing the pro-inflammatory cytokines IL-1β and IL-18 and enhancing the expression of tight-junction proteins occludin and ZO-1, as well as restoring the composition and diversity of gut microbiota. Results suggested that Se-B. longum DD98 effectively protected livers and intestines against the CPT-11-induced damages, and therefore, could be considered as a promising adjuvant therapeutic agent with CPT-11 for the cancer treatment.
伊立替康（CPT-11）是一种喜树碱化疗药物，主要用于治疗癌症。然而，其强烈的不良反应，如胃肠道和肝毒性，往往会降低患者的生活质量，并限制 CPT-11 的临床应用。硒（Se）和益生菌对 CPT-11 诱导毒性的保护作用已得到广泛报道。然而，富硒益生菌在 CPT-11 辅助治疗中的应用尚未得到充分探索。本研究旨在评估富硒长双歧杆菌 DD98（Se-B. longum DD98）作为化疗预防剂对减轻 CPT-11 化疗引起的肠道和肝脏毒性的体外和体内作用。结果表明，Se-B. longum DD98 可正向调节 CPT-11 诱导的人正常肝细胞（L-02）和大鼠小肠上皮细胞（IEC-6）系中异常细胞活力和氧化应激。体内实验表明，Se-B. longum DD98 通过改善体重减轻和腹泻等症状以及改善肝毒性和氧化应激的生化指标，显著减轻了肠道和肝脏毒性。此外，我们发现，Se-B. longum DD98 的保护作用主要基于减少促炎细胞因子 IL-1β 和 IL-18 的表达，增强紧密连接蛋白 occludin 和 ZO-1 的表达，以及恢复肠道微生物群落的组成和多样性。结果表明，Se-B. longum DD98 能有效保护肝脏和肠道免受 CPT-11 诱导的损伤，因此可考虑作为一种有前途的 CPT-11 癌症治疗辅助治疗剂。
