Inhibition of neovascularization in vivo by gold compounds.
As mononuclear cell infiltration and growth of pannus critically depend on synovial neovascularization in rheumatoid arthritis (RA), inhibition of the synovial blood vessels would have the potential to reduce rheumatoid inflammation. In this investigation, we studied the effect of gold sodium thiomalate (GST) and auranofin (AUR) on neovascularization in vivo by using a micropocket technique. Both GST and AUR suppressed rabbit corneal neovascularization in a dose-dependent fashion. Significant inhibition was observed by 3 mg/kg GST and 1 mg/kg AUR injected intravenously every other day. These injections maintained serum gold concentrations at the level of 2-5 micrograms/ml and less than 2 micrograms/ml in GST- and AUR-injected rabbits, respectively. These are concentrations attained in the serum or synovium of rheumatoid patients treated by gold compounds. Similar inhibition was observed by both intramuscular administration of GST and oral administration of AUR. In contrast, no inhibition was observed when non-steroidal anti-inflammatory drugs (NSAIDs; 20 mg/kg acetylsalicylic acid, 10 mg/kg ibuprofen and 10 mg/kg indomethacin) were injected intravenously on a daily basis. These results suggested that gold compounds have an antiangiogenic effect in vivo. The inhibition of neovascularization by gold compounds suggested that they may suppress rheumatoid synovitis by reducing the number of small blood vessels required for mononuclear cell infiltration and synovial tissue proliferation.
Saura
R
R
Department of Orthopaedic Surgery, Kobe University School of Medicine, Japan.
Matsubara
T
T
Mizuno
K
K
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D001310:Auranofin / Q000008:administration & dosage / Q000494:pharmacology*; D003315:Cornea / Q000098:blood supply* / Q000187:drug effects; D016510:Corneal Neovascularization / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006052:Gold Sodium Thiomalate / Q000008:administration & dosage / Q000494:pharmacology*; D007275:Injections, Intravenous; D008833:Microcirculation / Q000187:drug effects*; D008854:Microscopy, Electron; D011817:Rabbits; D013585:Synovitis / Q000188:drug therapy
D000894:Anti-Inflammatory Agents, Non-Steroidal; D006052:Gold Sodium Thiomalate; D001310:Auranofin