title: Baicalein attenuates vinorelbine-induced vascular endothelial cell injury and chemotherapeutic phlebitis in rabbits.
abstract: Chemotherapy is one of the major strategies for cancer treatment. Several antineoplastic drugs including vinorelbine (VRB) are commonly intravenously infused and liable to cause serious phlebitis. The therapeutic drugs for preventing this complication are limited. In this study, the mechanism of baicalein (BCN) was investigated on VRB-induced phlebitis in vivo and vascular endothelial cell injury in vitro. Treatment with BCN obviously attenuated vascular endothelial cell loss, edema, inflammatory cell infiltration and blood clots, and reduced the serum levels of TNF-α, IL-1β, IL-6 and ICAM-1 in the rabbit model of phlebitis induced by intravenous injection of VRB compared with vehicle. Further tests in vitro demonstrated that BCN lessened VRB-induced endothelial cell apoptosis, decreased intracellular ROS levels, suppressed phosphorylation of p38 and eventually inhibited activation of NF-κB signaling pathway. And these effects could be reversed by p38 agonist P79350. These results suggested that BCN exerted the protective effects against VRB-induced endothelial disruption in the rabbit model of phlebitis via inhibition of intracellular ROS generation and inactivation of p38/NF-κB pathway, leading to the decreased production of pro-inflammatory cytokines. Thus, BCN could be used as a potential agent for the treatment of phlebitis.
authors.affiliation: Zhejiang Chinese Medical University, Hangzhou 310053, China.
authors.forename: Gang-Feng
authors.initials: GF
authors.lastname: Ge
authors.affiliation: Zhejiang Medical Science and Education Development Center, Hangzhou 310006, China.
authors.forename: Wei-Wen
authors.initials: WW
authors.lastname: Shi
authors.affiliation: Key Laboratory of Experimental Animal and Safety Evaluation, Zhejiang Academy of Medical Sciences, Hangzhou 310013, China.
authors.forename: Chen-Huan
authors.initials: CH
authors.lastname: Yu
authors.affiliation: Key Laboratory of Experimental Animal and Safety Evaluation, Zhejiang Academy of Medical Sciences, Hangzhou 310013, China.
authors.forename: Xiao-Yin
authors.initials: XY
authors.lastname: Jin
authors.affiliation: Key Laboratory of Experimental Animal and Safety Evaluation, Zhejiang Academy of Medical Sciences, Hangzhou 310013, China.
authors.forename: Huan-Huan
authors.initials: HH
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Experimental Animal and Safety Evaluation, Zhejiang Academy of Medical Sciences, Hangzhou 310013, China.
authors.forename: Wen-You
authors.initials: WY
authors.lastname: Zhang
authors.affiliation: Zhejiang Chinese Medical University, Hangzhou 310053, China.
authors.forename: Lu-Chen
authors.initials: LC
authors.lastname: Wang
authors.affiliation: Zhejiang Chinese Medical University, Hangzhou 310053, China. Electronic address: Jellycook2002@163.com.
authors.forename: Bing
authors.initials: B
authors.lastname: Yu
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D044950:Flavanones / Q000494:pharmacology / Q000627:therapeutic use*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D010689:Phlebitis / Q000188:drug therapy* / Q000378:metabolism; D011817:Rabbits; D011897:Random Allocation; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000633:toxicity; D000077235:Vinorelbine
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D044950:Flavanones; D018836:Inflammation Mediators; D017382:Reactive Oxygen Species; C006680:baicalein; D014747:Vinblastine; D000077235:Vinorelbine
keywords: Apoptosis; Cytotoxicity; Inflammation; MAPK; NF-κB; Oxidant stress