Luo Zhiguo, Dong Xiaoxia, Ke Qing, Duan Qiwen, Shen Li
Department of Clinical Oncology, Taihe Hospital, Hubei University of Medicine, Hubei 442000, P.R. China.
Department of Pharmacology, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
Oncol Rep. 2014 Nov;32(5):2215-22. doi: 10.3892/or.2014.3463. Epub 2014 Sep 3.
Chitooligosaccharides (COS) are hydrolyzed products of chitosan and have been proven to exhibit various biological functions. The aims of this study were to investigate the mechanisms underlying the hepatoprotective effects of COS against ethanol-induced oxidative stress in vitro. Human L02 normal liver cells were pretreated with COS (0.25, 0.5 and 1.0 mg/ml) and then hepatotoxicity was stimulated by the addition of ethanol (80 mM). Pretreatment with COS protected L02 cells from ethanol-induced cell cytotoxicity through inhibition of reactive oxygen species generation. Furthermore, ethanol-induced lipid peroxidation and glutathione depletion was inhibited by COS. The antioxidant potential of COS was correlated with the induction of antioxidant genes including HO-1, NQO1 and SOD via the transcriptional activation of nuclear factor erythroid-2‑related factor-2 (Nrf2). Additionally, the protective effects of COS against ethanol were blocked by Nrf2 knockdown. Moreover, signal transduction studies showed that COS was able to suppress the ethanol-induced phosphorylation of p38 MAPK, JNK and ERK. In conclusion, the COS-mediated activation of Nrf2 and reduction of MAPK phosphorylation may be important for its hepatoprotective action.
壳寡糖（COS）是壳聚糖的水解产物，已被证明具有多种生物学功能。本研究的目的是探讨COS在体外对乙醇诱导的氧化应激的肝保护作用机制。人L02正常肝细胞用COS（0.25、0.5和1.0mg/ml）预处理，然后加入乙醇（80mM）诱导肝毒性。COS预处理通过抑制活性氧的产生保护L02细胞免受乙醇诱导的细胞毒性。此外，COS抑制了乙醇诱导的脂质过氧化和谷胱甘肽耗竭。COS的抗氧化潜力与通过核因子红细胞2相关因子2（Nrf2）的转录激活诱导抗氧化基因包括HO-1、NQO1和SOD有关。此外，Nrf2敲低阻断了COS对乙醇的保护作用。此外，信号转导研究表明，COS能够抑制乙醇诱导的p38 MAPK、JNK和ERK磷酸化。总之，COS介导的Nrf2激活和MAPK磷酸化的减少可能对其肝保护作用很重要。
