title: Protective effect of tea polyphenols on renal ischemia/reperfusion injury via suppressing the activation of TLR4/NF-κB p65 signal pathway.
abstract: 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.
authors.affiliation: Department of Nephrology, The Second Hospital of Tianjin Medical University, Tianjin 300211, China.
authors.forename: Yan-Wei
authors.initials: YW
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Tianjin Huanhu Hospital, Tianjin 300060, China. Electronic address: yzhangtj@yeah.net.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, Tianjin Huanhu Hospital, Tianjin 300060, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Tianjin institute of medical and pharmaceutical sciences, Tianjin 300000, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Tianjin Nan Kai Hospital, Tianjin 300100, China.
authors.forename: Jian-Bo
authors.initials: JB
authors.lastname: Yu
authors.affiliation: Department of Anesthesiology, Tianjin Huanhu Hospital, Tianjin 300060, China.
authors.forename: Hong-Tao
authors.initials: HT
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Tianjin Huanhu Hospital, Tianjin 300060, China.
authors.forename: Bin-Bin
authors.initials: BB
authors.lastname: Tan
authors.affiliation: Department of Anesthesiology, Tianjin Huanhu Hospital, Tianjin 300060, China.
authors.forename: Lian-Hao
authors.initials: LH
authors.lastname: Jiang
authors.affiliation: Department of Anesthesiology, Tianjin Huanhu Hospital, Tianjin 300060, China.
authors.forename: Ya-Xin
authors.initials: YX
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Tianjin Huanhu Hospital, Tianjin 300060, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Anesthesiology, Tianjin Huanhu Hospital, Tianjin 300060, China.
authors.forename: Xiu-Shan
authors.initials: XS
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Tianjin Huanhu Hospital, Tianjin 300060, China.
authors.forename: Wen-Sheng
authors.initials: WS
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Tianjin Huanhu Hospital, Tianjin 300060, China.
authors.forename: Hai-Gen
authors.initials: HG
authors.lastname: Liu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D001806:Blood Urea Nitrogen; D028241:Camellia sinensis / Q000737:chemistry*; D002374:Catalase / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects; D007684:Kidney Tubules / Q000098:blood supply / Q000187:drug effects; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008297:Male; D018375:Neutrophil Activation / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000008:administration & dosage*; D059808:Polyphenols / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000975:Antioxidants; D053583:Interleukin-1beta; D015850:Interleukin-6; D010936:Plant Extracts; D059808:Polyphenols; D017382:Reactive Oxygen Species; C498145:Rela protein, rat; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10; D003404:Creatinine; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase
keywords: Antioxidant; Astragalus mongholicus; Rat; Renal ischemia–reperfusion; TLR4/NF-κB p65 signal pathway; Tea polyphenols