Abstract
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 Ecklonia cava (E. cava) 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 E. cava 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.
Highlights
Ischemia/reperfusion (I/R) injury, which occurs when blood supply to tissues or organs is restored after ischemia, leads to more tissue damage than ischemia itself by enhancing the inflammatory reaction in the reperfused tissue [1].Renal I/R injury is a major pathophysiology of acute kidney injury (AKI) and can induce AKI after kidney transplantation, partial nephrectomy, renal artery angioplasty, aortic aneurysm surgery, and elective urological surgery when blood supply to the kidney is stopped or decreased during surgery [2].In addition to AKI, I/R injury leads to the loss of tubular epithelial cell (TEC) function, resulting inMar
In the pre-hypoxia model, the high-mobility group protein B1 (HMGB1) level was increased by H/R injury in both TEC lysate and supernatant (Figure 1A,B), suggesting that TECs injured by H/R increased the synthesis and release of HMGB1
In the post-hypoxia treatment model, the HMGB1 level increased by H/R injury was decreased by adding E. cava extracts before reperfusion in both TEC lysate and supernatant
Summary
Ischemia/reperfusion (I/R) injury, which occurs when blood supply to tissues or organs is restored after ischemia, leads to more tissue damage than ischemia itself by enhancing the inflammatory reaction in the reperfused tissue [1].Renal I/R injury is a major pathophysiology of acute kidney injury (AKI) and can induce AKI after kidney transplantation, partial nephrectomy, renal artery angioplasty, aortic aneurysm surgery, and elective urological surgery when blood supply to the kidney is stopped or decreased during surgery [2].In addition to AKI, I/R injury leads to the loss of tubular epithelial cell (TEC) function, resulting inMar. Ischemia/reperfusion (I/R) injury, which occurs when blood supply to tissues or organs is restored after ischemia, leads to more tissue damage than ischemia itself by enhancing the inflammatory reaction in the reperfused tissue [1]. Renal I/R injury is a major pathophysiology of acute kidney injury (AKI) and can induce AKI after kidney transplantation, partial nephrectomy, renal artery angioplasty, aortic aneurysm surgery, and elective urological surgery when blood supply to the kidney is stopped or decreased during surgery [2]. In addition to AKI, I/R injury leads to the loss of tubular epithelial cell (TEC) function, resulting in. Mar. Drugs 2019, 17, 602; doi:10.3390/md17110602 www.mdpi.com/journal/marinedrugs. Mar. Drugs 2019, 17, 602 delayed graft function and acute or chronic rejection of the transplanted kidney [3]. To decrease the incidence of AKI after surgeries accompanied by I/R injury, treatments to decrease I/R injury should be developed
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