Mangiferin attenuates renal ischemia-reperfusion injury by inhibiting inflammation and inducing adenosine production.

Ischemia reperfusion injury (IRI) is a leading cause of acute kidney injury, which is associated with high morbidity. The aims of the present study were to examine whether mangiferin attenuates renal IRI in an animal model and to identify the underlying mechanism(s). Male mice were subjected to right renal ischemia for 30min followed by reperfusion for 24h or to a sham operation during which the left kidney was removed. After the 24h reperfusion, all mice were humanely euthanized and kidney tissues collected. Renal damage and apoptosis were investigated by examining hematoxylin and eosin-stained tissues, and by TUNEL assay and immunohistochemistry. Renal function was examined by measuring the concentrations of creatinine, blood urea nitrogen, and potassium (K(+)) in the serum. MPO activity, the levels of NO, TNF-α, IL-1β, and adenosine, and CD73 expression in renal tissue were also examined. Mangiferin reduced ischemia reperfusion-induced injury, improved kidney function, and inhibited both proinflammatory responses and tubular apoptosis. In addition, treatment with mangiferin increased adenosine production and CD73 expression in kidney's suffering IRI. Mangiferin appears to attenuate renal IRI by inhibiting proinflammatory responses and tubular apoptosis and by increasing adenosine production. These effects are associated with the adenosine-CD73 signaling pathway.

Wang B ，Wan J ，Gong X ，Kuang G ，Cheng X ，Min S ... -  《-》

Protective effect of tea polyphenols on renal ischemia/reperfusion injury via suppressing the activation of TLR4/NF-κB p65 signal pathway.

Tea polyphenols (TP) was investigated in rats for its protective effect on renal ischemia/reperfusion injury (RIRI). Rats were randomized into groups as follows: (I) sham group (n=10); (II) RIRI group (n=10); (III) RIRI+TP (100mg/kg) group (n=5); (IV) RIRI+TP (200mg/kg) group (n=5); (V) RIRI+TP+ Astragalus mongholicus aqueous extract (AMAE) (300 mg/kg+100mg/kg) group (n=5). For the IRI+TP groups, rats were orally given with tea polyphenols (100, 200 and 300 mg/kg body weight) once daily 10 days before induction of ischemia, followed by renal IRI. For the sham group and RIRI group, rats were orally given with equal volume of saline once daily 10 days before induction of ischemia, followed by renal IRI. Results showed that tea polyphenol pretreatment significantly suppressed ROS level and MDA release. On the other hand, in rats subjected to ischemia-reperfusion, the activities of endogenous antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) and glutathione peroxidase (GSH-Px) showed recovery, whereas the levels of urea nitrogen and serum creatinine were reduced by administration of tea polyphenols orally for 10 days prior to ischemia-reperfusion. Moreover, tea polyphenol pretreatment significantly decreased TLR4 and NF-κB p65 protein expression levels in RIRI rats. At the same time, tea polyphenol pretreatment attenuated the increased level of serum IL-1β, IL-6, ICAM-1 and TNF-α, and enhanced IL-10 production in RIRI rats. Furthermore, tea polyphenol pretreatment significantly decreased renal epithelial tubular cell apoptosis induced by renal ischemia/reperfusion, alleviating renal ischemia/reperfusion injury. These results cumulatively indicate that tea polyphenol pretreatment could suppress the TLR4/NF-κB p65 signaling pathway, protecting renal tubular epithelial cells against ischemia/reperfusion-induced apoptosis, which implies that antioxidants may be a potential and effective agent for prevention of the ischemic/reperfusion injury through the suppression extrinsic apoptotic signal pathway induced by TLR4/NF-κB p65 signal pathway. Moreover, supplement of AMAE can increased renal protection effect of TP.

Li YW ，Zhang Y ，Zhang L ，Li X ，Yu JB ，Zhang HT ，Tan BB ，Jiang LH ，Wang YX ，Liang Y ，Zhang XS ，Wang WS ，Liu HG ... -  《-》

Ferulic Acid Protected from Kidney Ischemia Reperfusion Injury in Mice: Possible Mechanism Through Increasing Adenosine Generation via HIF-1α.

Zhou Q ，Gong X ，Kuang G ，Jiang R ，Xie T ，Tie H ，Chen X ，Li K ，Wan J ，Wang B ... -  《-》

CD73 protects kidney from ischemia-reperfusion injury through reduction of free radicals.

Renal ischemia-reperfusion injury (IRI) may cause severe systemic diseases. Extracellular adenosine is anti-inflammatory especially during hypoxemia. As ecto-5'-nucleotidase (CD73) is the rate-limiting enzyme for extracellular adenosine generation, it may protect renal IRI through adenosine production. In the current studies, we investigated the effects of CD73 in genetically modified mice. We found that renal IRI caused more serious histological injury, vascular permeability, and lipid peroxidation in CD73(-/-) than that in CD73(+/+) mice. In addition, AMP and free radical concentrations were much higher in CD73(-/-) than that in CD73(+/+) mice. Our data support the fact that CD73 may protect the kidney from IRI through adenosine production and a reduction of free radicals.

Jian R ，Sun Y ，Wang Y ，Yu J ，Zhong L ，Zhou P ... -  《-》

The volatile anesthetic isoflurane induces ecto-5'-nucleotidase (CD73) to protect against renal ischemia and reperfusion injury.

Kim M ，Ham A ，Kim JY ，Brown KM ，D'Agati VD ，Lee HT ... -  《-》