A novel class of copper(II)- and zinc(II)-bound non-steroidal anti-inflammatory drugs that inhibits acute inflammation in vivo

Rajesh Puranik, Shisan Bao*, Antonio M. Bonin, Ravinder Kaur, Jane E. Weder, Llewellyn Casbolt, Trevor W. Hambley, Peter A. Lay, Philip J. Barter, Kerry Anne Rye

*Corresponding author for this work

Research output: Contribution to journalArticle

17 Citations (Scopus)

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. Conclusion: 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.

Original languageEnglish
Article number9
Pages (from-to)1-7
Number of pages7
JournalCell and Bioscience
Volume6
Issue number1
DOIs
Publication statusPublished - 6 Feb 2016
Externally publishedYes

Keywords

  • NSAIDs
  • indomethacin
  • copper(II) indomethacin
  • copper(II) ACM
  • zinc(II) ACM

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