title: Rifampicin inhibits the retinal neovascularization in vitro and in vivo.
abstract: Rifampicin, an antibacterial drug widely used in the treatment of tuberculosis and leprosy, has recently been reported to have anti-oxidative and anti-apoptotic effects. However, its anti-angiogenic effect has not been investigated. We examined its anti-angiogenic effect on tube formation and proliferation by human umbilical vein endothelial cells (HUVECs) in vitro and on retinal neovascularization in a murine oxygen-induced retinopathy model in vivo. In addition, we explored the potential mechanisms for its anti-angiogenic effect. Rifampicin significantly suppressed HUVEC tube formation and proliferation, and its effects appeared to be mediated at least in part through inhibition of extracellular signal-regulated kinase (ERK) 1/2 phosphorylation. Retinal neovasuclarization was induced in neonatal mice by returning the retina to normoxia (21% O2) after exposure to hyperoxia (75% O2) from postnatal day 7 (P7) to P12. Rifampicin was given subcutaneously at 20mg/kg once a day from immediately after hyperoxia (P12) to P16. At P17, flat-mounted retinas were prepared and evaluated for pathological and physiological angiogenesis. Rifampicin significantly suppressed retinal neovascularization (versus vehicle treatment), but revascularization of the capillary-free area did not differ between vehicle and rifampicin treatment. Rifampicin has anti-angiogenic effects in vitro and in vivo, and may be useful as an anti-angiogenic agent in the treatment of retinal neovascularization diseases.
authors.affiliation: Department of Biofunctional Evaluation, Molecular Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, 502-8585 Gifu, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Chikaraishi
authors.forename: Nozomu
authors.initials: N
authors.lastname: Matsunaga
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Shimazawa
authors.forename: Hideaki
authors.initials: H
authors.lastname: Hara
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010100:Oxygen; D010766:Phosphorylation; D015861:Retinal Neovascularization / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D012293:Rifampin / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D020533:Angiogenesis Inhibitors; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D010100:Oxygen; D012293:Rifampin