Low Molecular Weight Fucoidan against Renal Ischemia–Reperfusion Injury via Inhibition of the MAPK Signaling Pathway

Abstract

BackgroundIschemia reperfusion injury (IRI) is a leading cause of acute kidney injury (AKI) in both native and transplanted kidneys. The objective of the present study was to evaluate whether low-molecular-weight fucoidan (LMWF) could attenuate renal IRI in an animal model and in vitro cell models and study the mechanisms in which LMWF protected from IRI.Methodology/Principal FindingsMale mice were subjected to right renal ischemia for 30 min and reperfusion for 24 h, or to a sham operation with left kidney removed. Kidneys undergone IR showed characteristic morphological changes, such as tubular dilatation, and brush border loss. However, LMWF significantly corrected the renal dysfunction and the abnormal levels of MPO, MDA and SOD induced by IR. LMWF also inhibited the activation of MAPK pathways, which consequently resulted in a significant decrease in the release of cytochrome c from mitochondria, ratios of Bax/Bcl-2 and cleaved caspase-3/caspase-3, and phosphorylation of p53. LMWF alleviated hypoxia-reoxygenation or CoCl2 induced cell viability loss and ΔΨm dissipation in HK2 renal tubular epithelial cells, which indicates LMWF may result in an inhibition of the apoptosis pathway through reducing activity of MAPK pathways in a dose-dependent manner.Conclusions/SignificanceOur in vivo and in vitro studies show that LMWF ameliorates acute renal IRI via inhibiting MAPK signaling pathways. The data provide evidence that LMWF may serve as a potential therapeutic agent for acute renal IRI.

Low-molecular-weight fucoidan protects endothelial function and ameliorates basal hypertension in diabetic Goto-Kakizaki rats

“…19 In addition, it has obvious protective effects against brain inflammation and renal ischemia-reperfusion injury. 17,18 Here we demonstrated that LMWF corrected the impaired endothelium-dependent vasorelaxation and eNOS function in diabetic rats. Importantly, these effects of LMWF are through the protections of eNOS phosphorylation at Ser1177 residue and its expression in vasoendothelium, highlighting its effectiveness on dysfunctional endothelium, and thus anti-hypertension in diabetic animals.…”

“…In previous studies, we have successfully prepared and characterized a low-molecular-weight fucoidan (LMWF, 7000 Da) from L aminaria japonica that shares similar biological activities with other fucoidans. [16][17][18] In particular, LMWF has an advantage over the others in that it exerts antithrombotic effect without impacting coagulation, 19 thus it has a lower hemorrhagic risk than other fucoidans. 14,15 Therefore, we hypothesized that LMWF may protect against the endothelial and vascular disorders caused by diabetes.…”

Mitogen-Activated Protein Kinases and Hypoxic/Ischemic Nephropathy

“…However, all of their phosphorylation levels are altered under certain conditions. For instance, the phosphorylation of p38, ERK1/2 and JNK is significantly increased during hypoxia-reoxygenation in the human kidney cells [28]. Our recent studies found that ERK1/2 and p38 were dramatically activated in rat kidney epithelial cells (NRK-52E) under hypoxic conditions (Fig.…”

Aloperine Protects Mice against Ischemia-Reperfusion (IR)-Induced Renal Injury by Regulating PI3K/AKT/mTOR Signaling and AP-1 Activity

“…However, MAP kinases and PI3K/Akt/mTOR sig naling are thought to be implicated in the initiation and progression of IRinduced inflammatory responses (51)(52)(53)(54). We first examined the impact of aloperine on MAP kinase activities.…”