背景:阿霉素(DOX)是一种众所周知的化学治疗剂,由于多器官损伤而引起严重的不良反应,包括心脏毒性,肾毒性,神经毒性,和肝毒性。DOX诱导的器官毒性的机制可能归因于氧化应激(OS)和,因此,炎症信号通路的激活,凋亡,和阻断自噬。作为糖脂类型的生物表面活性剂,是天然产品,具有独特的性能和广泛的应用归因于其抗氧化和抗炎特性。
目的:从香蕉果皮上生长的酿酒酵母生产低成本SL,并研究其对DOX诱导的肝毒性的可能保护作用。
方法:对酵母进行局部分离和分子鉴定,然后用FTIR对产生的SL进行了表征,1HNMR和LC-MS/MS光谱。后期,将32只雄性Wistar大鼠随机分为4组;对照组(口服盐水),SLs(200mg/kg,p.o),DOX(10mg/kg;i.p.),和SL+DOX(200mg/kgp.o.,10mg/kg;i.p.分别)。肝功能测试(LFTs),氧化应激,炎症,细胞凋亡以及自噬标志物进行了研究。
结果:SL的产量为49.04%,用SL处理可改善LFT,增强Nrf2和抑制NF-κB,IL-6,IL-1β,p38、caspase一3和Bax/Bcl2比值除增进自噬外,与DOX组比拟。
结论:我们的研究结果揭示了SLs对抗DOX诱导的大鼠肝毒性的新的有希望的保护作用。
BACKGROUND: Doxorubicin (DOX) is a well-known chemotherapeutic agent which causes serious adverse effects due to multiple organ damage, including cardiotoxicity, nephrotoxicity, neurotoxicity, and hepatotoxicity. The mechanism of DOX-induced organ toxicity might be attributed to oxidative stress (OS) and, consequently, activation of inflammatory signaling pathways, apoptosis, and blockage of autophagy.
Sophorolipids (SLs) as a glycolipid type of biosurfactants, are natural products that have unique properties and a wide range of applications attributed to their antioxidant and anti-inflammatory properties.
OBJECTIVE: Production of low-cost SLs from Saccharomyces cerevisiae grown on banana peels and investigating their possible protective effects against DOX-induced hepatotoxicity.
METHODS: The yeast was locally isolated and molecularly identified, then the yielded SLs were characterized by FTIR, 1H NMR and LC-MS/MS spectra. Posteriorly, thirty-two male Wistar rats were randomly divided into four groups; control (oral saline), SLs (200 mg/kg, p.o), DOX (10 mg/kg; i.p.), and SL + DOX (200 mg/kg p.o.,10 mg/kg; i.p., respectively). Liver function tests (LFTs), oxidative stress, inflammatory, apoptosis as well as autophagy markers were investigated.
RESULTS: SLs were produced with a yield of 49.04% and treatment with SLs improved LFTs, enhanced Nrf2 and suppressed NF-κB, IL-6, IL-1β, p38, caspase 3 and Bax/Bcl2 ratio in addition to promotion of autophagy when compared to DOX group.
CONCLUSIONS: Our results revealed a novel promising protective effect of SLs against DOX-induced hepatotoxicity in rats.