title: A novel class of copper(II)- and zinc(II)-bound non-steroidal anti-inflammatory drugs that inhibits acute inflammation in vivo.
abstract: BACKGROUND
  The ability of Zn(II) and Cu(II) metal complexes of non-steroidal anti-inflammatory drugs (NSAIDs) to inhibit acute arterial inflammation in vivo has been studied.
  
  
  RESULTS
  When acute vascular inflammation was induced in normocholesterolemic New Zealand White rabbits by inserting a non-occlusive silastic collar around the common carotid artery, a single oral dose of Cu(II)-indomethacin (Cu(II)Indo, 3 mg/kg) administered by laparotomy achieved a 67 % (8.2 ± 1.7 vs. 2.7 ± 0.4 image units, p < 0.05) reduction in endothelial expression of vascular cell adhesion molecule-1 (VCAM-1) but did not inhibit endothelial intercellular adhesion molecule (ICAM-1) expression significantly. Treatment with Cu(II)-acemetacin (Cu(II)ACM, 3 mg/kg) led to a profound 88 % (8.2 ± 1.7 vs. 1.0 ± 0.5 image units, p < 0.01) reduction in endothelial VCAM-1 expression but did not inhibit ICAM-1 expression, while treatment with Zn(II)-acemetacin (Zn(II)ACM, 3 mg/kg) led to an 84 % (19.3 ± 1.0 vs. 3.1 ± 1.2 image units, p < 0.01) reduction in endothelial ICAM-1 expression and did not inhibit VCAM-1 expression. No adverse gastric, hepatic or renal effects were observed in treated animals.
  
  
  CONCLUSIONS
  These findings provide the "proof of concept" that this novel class of drug, where there is complexation of NSAIDs with metal ions, has substantial anti-inflammatory effects in an animal model of acute vascular inflammation with the possibility of low rates of adverse effects.
authors: The Heart Research Institute, 7, Eliza St., Sydney, NSW 2042 Australia ; Department of Cardiology, Royal Prince Alfred Hospital, Missenden Rd, Camperdown, NSW 2050 Australia.
authors: Rajesh
authors: R
authors: Puranik
authors: The Heart Research Institute, 7, Eliza St., Sydney, NSW 2042 Australia ; Discipline of Pathology, D17, The School of Medical Sciences and Bosch Institute, The University of Sydney, Sydney, NSW 2006 Australia.
authors: Shisan
authors: S
authors: Bao
authors: The School of Chemistry, The University of Sydney, Sydney, NSW 2006 Australia.
authors: Antonio M
authors: AM
authors: Bonin
authors: The School of Chemistry, The University of Sydney, Sydney, NSW 2006 Australia.
authors: Ravinder
authors: R
authors: Kaur
authors: The School of Chemistry, The University of Sydney, Sydney, NSW 2006 Australia.
authors: Jane E
authors: JE
authors: Weder
authors: Casbolt & Associates Pty Ltd, Sydney, Australia.
authors: Llewellyn
authors: L
authors: Casbolt
authors: The School of Chemistry, The University of Sydney, Sydney, NSW 2006 Australia.
authors: Trevor W
authors: TW
authors: Hambley
authors: The School of Chemistry, The University of Sydney, Sydney, NSW 2006 Australia.
authors: Peter A
authors: PA
authors: Lay
authors: The Heart Research Institute, 7, Eliza St., Sydney, NSW 2042 Australia.
authors: Philip J
authors: PJ
authors: Barter
authors: The Heart Research Institute, 7, Eliza St., Sydney, NSW 2042 Australia ; Lipid Research Group, Centre for Vascular Research, The University of New South Wales, Sydney, NSW 2052 Australia.
authors: Kerry-Anne
authors: KA
authors: Rye
keywords: Copper(II) ACM; Copper(II) indomethacin; Indomethacin; NSAIDs; Zinc(II) ACM