Pyrogallol-Phloroglucinol-6,6-Bieckol from Ecklonia cava Attenuates Tubular Epithelial Cell (TCMK-1) Death in Hypoxia/Reoxygenation Injury

• Published in: Marine drugs Vol. 17; no. 11; p. 602
• Main Authors: Son, Myeongjoo, Oh, Seyeon, Choi, Chang Hu, Park, Kook Yang, Son, Kuk Hui, Byun, Kyunghee
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 24.10.2019; MDPI
• Subjects: Animals; Apoptosis; Cell death; Cell Line; Complications; Cytokines; Cytokines - metabolism; Dioxins - pharmacology; Ecklonia cava; Epithelial cells; Epithelial Cells - drug effects; Epithelium; HMGB1 protein; HMGB1 Protein - metabolism; Hypoxia; Hypoxia - chemically induced; Hypoxia - drug therapy; Inflammation; Injuries; Interleukin 6; Ischemia; ischemia-reperfusion injury; kidney; Kidney - metabolism; Kinases; MAP Kinase Signaling System - drug effects; Mice; Mortality; NF-kappa B - metabolism; NF-κB protein; Phaeophyceae - chemistry; Phloroglucinol; phlorotannins; Polyphenols; Pyrogallol; Pyrogallol - pharmacology; Reperfusion; Research methodology; Signal Transduction; Signaling; Surgery; Tannins - pharmacology; TLR4 protein; Toll-Like Receptor 4 - metabolism; Toll-like receptors; Tumor necrosis factor-TNF; Tumor necrosis factor-α; United States > US; ischemia-reperfusion injury; kidney; Ecklonia cava; phlorotannins
• ISSN: 1660-3397; 1660-3397
• DOI: 10.3390/md17110602

The hypoxia/reoxygenation (H/R) injury causes serious complications after the blood supply to the kidney is stopped during surgery. The main mechanism of I/R injury is the release of high-mobility group protein B1 (HMGB1) from injured tubular epithelial cells (TEC, TCMK-1 cell), which triggers TLR4 or RAGE signaling, leading to cell death. We evaluated whether the extracts of would attenuate TEC death induced by H/R injury. We also evaluated which phlorotannin-dieckol (DK), phlorofucofuroeckol A (PFFA), pyrogallol phloroglucinol-6,6-bieckol (PPB), or 2,7-phloroglucinol-6,6-bieckol (PHB)-would have the most potent effect in the context of H/R injury. We used for pre-hypoxia treatment, in which the phlorotannins from extracts were added before the onset of hypoxia, and a post- hypoxia treatment, in which the phlorotannins were added before the start of reperfusion. PPB most effectively reduced HMGB1 release and the expression of TLR4 and RAGE induced by H/R injury in both pre- and post-hypoxia treatment. PPB also most effectively inhibited the expression of NF-kB and release of the inflammatory cytokines TNF-α and IL-6 in both models. PPB most effectively inhibited cell death and expression of cell death signaling molecules such as Erk/pErk, JNK/pJNK, and p38/pp38. These results suggest that PPB blocks the HGMB1-TLR4/RAGE signaling pathway and decreases TEC death induced by H/R and that PPB can be a novel target for renal H/R injury therapy.