Pyrrolidine dithiocarbamate restores gastric damages and suppressive autophagy induced by hydrogen peroxide. (February 2015)

• Record Type: Journal Article
• Authors: Duan, J. L.; Yin, J.; Ren, W. K.; Wu, M. M.; Chen, S.; Cui, Z. J.; Wu, X.; Huang, R. L.; Li, T. J.; Yin, Y. L.
• Is Part Of: Free radical research. Volume 49:Number 2(2015:Feb.)
• Page Start: 210
• Page End: 218
• Publication Date: 2015-02
• Subjects: Free radicals (Chemistry) -- Periodicals; Antioxidants -- Periodicals; Vitamin C -- Periodicals; Vitamin E -- Periodicals; 541.224
• DOI: 10.3109/10715762.2014.993627
• Languages: English
• ISSNs: 1071-5762

Abstract

<abstract> <title>Abstract</title> <p>It is well known that gastric barrier is very important for protecting host from various insults. Simultaneously, autophagy serving as a prominent cytoprotective and survival pathway under oxidative stress conditions is being increasingly recognized. Thus, this study was conducted for investigating the effect of pyrrolidine dithiocarbamate (PDTC) on gastric barrier function and autophagy under oxidative stress induced by intragastric administration of hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>). The gastric tight junction proteins [zonula occludens-1 (ZO1), occludin, and claudin1], autophagic proteins [microtubule-associated protein light chain 3I(LC3I), LC3II, and beclin1], and nuclear factor kappa B (NF-κB) signaling pathway (p65 and IκB kinase α/β) were determined by Western blot. The results showed that H<sub>2</sub>O<sub>2</sub> exposure disturbed gastric barrier function with decreased expression of ZO1, occludin, and claudin1, and reduced gastric autophagy with decreased conversion of LC3I into LC3II in mice. However, treatment with PDTC restored these adverse effects evidenced by increased expression of ZO1 and claudin1 and increased conversion of LC3I into LC3II. Meanwhile, H<sub>2</sub>O<sub>2</sub> exposure decreased normal human gastric epithelial mucosa cell line (GES-1) viability in a concentration-dependent way. However, after being exposed to H<sub>2</sub>O<sub>2</sub>, GES-1 exhibited autophagic response which was inconsistent with our <italic>in vivo</italic> results in mice, while PDTC failed to decrease autophagy in GES-1 induced by H<sub>2</sub>O<sub>2</sub>. Simultaneously, the beneficial effect of PDTC on gastric damage and autophagy in mice might be independent of inhibition of NF-κB. In conclusion, PDTC treatment restores gastric damages and reduced autophagy induced by H<sub>2</sub>O<sub>2</sub>. Therefore, PDTC may serve as a potential adjuvant therapy for gastric damages.</p> </abstract>